复方芪麻胶囊治疗单纯收缩期高血压机制与临床研究
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摘要
一、研究背景
当今,单纯收缩期高血压(ISH)已经成为威胁人类健康的主要疾病之一,随着我国老年人口数量的不断增加,ISH的发病率在我国亦呈逐渐上升趋势。已有研究证实ISH是老年人群中最常见的高血压亚型,占老年高血压人群半数以上。同时ISH是老年人重要的心血管危险因素之一,其与心血管病的发生率和病死率呈正相关,其心血管并发症的发病率和病死率是血压正常者的3倍,且与早期肾功能损害关系密切。尽管人类已花费了大量人力、财力研究治疗ISH的有效药物,但至目前为止其均存在不可避免的副作用。因此从中医药方面着手,寻求出治疗ISH的有效药物已经成为高血压防治领域的一重要课题。目前为止,虽然已有很多报道治疗ISH的中药制剂,但有关治疗ISH的复方成药及关于这些中药制剂治疗ISH的机制研究未见报道,本课题即打算在此领域作些有益的探索。
本研究所用制剂复方芪麻胶囊是王清海教授基于中医基础理论,认真总结现代高血压病的中医辨证分型,结合自己数十载行医经验研制出的经验方。多年临床实践证实复方芪麻胶囊对于高血压,尤其是老年ISH有确切疗效。有研究证明复方芪麻胶囊能有效降低24h、白昼及夜间的血压,减轻血压负荷,对心、脑、肾等靶器官有保护作用。但究竟其通过何种机制起到治疗ISH的作用尚不明确,本课题拟通过临床观察评估复方芪麻胶囊治疗ISH的疗效及安全性,同时通过实验研究初步探讨复方芪麻胶囊治疗ISH的机制。
二、实验研究
1.目的
(1)观察复方芪麻胶囊对ISH大鼠血清中Hcy水平的干预情况,明确复方芪麻胶囊治疗ISH的机制；
(2)观察复方芪麻胶囊对实验大鼠血压及血脂相关指标的干预疗效,明确复方芪麻胶囊治疗ISH的机制;
(3)从病理学方面明确复方芪麻胶囊改善实验动物动脉硬化的程度,为复方芪麻胶囊治疗ISH提供实验依据。
2.方法与内容
采用SD大鼠,随机分为6组：健康对照组、空白组对照组、硝苯地平组、复方芪麻胶囊低剂量组、中剂量组和高剂量组。采用WVK模式建立大鼠单纯收缩期高血压模型,采用电镜酶细胞化学和分子生物学及免疫组化等方法,从整体、细胞乃至分子水平探讨复方芪麻胶囊治疗ISH的机制。本实验共分为三个部分。实验一：采用WVK模式制造大鼠单纯收缩期高血压模型,观察复方芪麻胶囊对ISH大鼠血清中Hcy水平的干预情况,明确复方芪麻胶囊治疗ISH的机制。实验二：观察复方芪麻胶囊对大鼠血压及血脂的干预疗效,明确其降压机制。实验三：从病理学角度观察复方芪麻胶囊改善ISH大鼠腹主动脉硬化的程度,探讨复方芪麻胶囊改善动脉粥样硬化的机制。
3.结果
(1)造模前后血压比较：造模组与健康组大鼠造模后同期收缩压比较,自第三周起,收缩压明显升高,经t检验,P<0.05,差异有统计学意义；造模组与健康组同期舒张压比较,经t检验,P>0.05,差异无统计学意义。造模组造模前后自身收缩压比较,经t检验,P<0.05,差异有统计学意义；造模前后自身舒张压比较,经t检验,P>0.05,差异无统计学意义,说明造模成功。
(2)造模后各组与健康组比较,Hcy水平存在着明显差异(P<0.05),说明ISH发生时,血Hcy水平升高。单纯收缩期高血压的发生与高同型半胱氨酸血症密切相关。
(3)治疗前后血Hey水平自身比较：低、中、高剂量组存在显著性差异(P<0.05)。说明复方芪麻胶囊能有效降低ISH大鼠血Hcy水平。
(4)治疗后与空白组比较：低、中、高剂量组大鼠血Hcy水平均有所下降,其中高剂量组下降最明显,存在显著性差异(P<0.01)。说明复方芪麻胶囊能有效降低ISH大鼠血Hcy水平,疗效呈剂量依赖性。
(5)治疗前后收缩压比较：与空白组同期比较,自第一周起硝苯地平组收缩压即见明显降低,经t检验,P<0.01,差异具有统计学意义,而复方芪麻胶囊各剂量组收缩压则自第三周起出现明显下降,中、高剂量组差异具有显著性(P<0.05),具有统计学意义。治疗后第四周,复方芪麻胶囊高剂量组与硝苯地平组血压比较,差异无统计学意义(P>0.05),说明复方芪麻胶囊高剂量降低收缩压疗效与硝苯地平片相当。与空白组同期及治疗前自身比较,复方芪麻胶囊低、中、高剂量组收缩压均明显下降,差异具有统计学意义(P<0.05),其中高剂量组血压下降最明显(P<0.01),说明复方芪麻胶囊降低收缩压的疗效存在着量效关系。
(6)治疗前后舒张压比较：与空白组同期和治疗前自身比较,硝苯地平组治疗后舒张压下降明显,经t检验,P<0.05,差异具有统计学意义。复方芪麻胶囊各剂量组治疗后舒张压,与空白组同期及治疗前自身比较,差异无统计学意义(P>0.05),说明复方芪麻胶囊对舒张压影响较小。
(7)治疗后各组大鼠血脂水平比较：空白组与健康组比较,TC、TG、LDL-C、LP(a)含量明显升高,存在显著性差异(P<0.05),说明ISH大鼠存在脂代谢紊乱。复方芪麻胶囊各剂量组与空白组比较,TG、TC、LDL、LP(a)含量均明显减低,存在显著性差异(P<0.05),说明复方芪麻胶囊能有效干预ISH大鼠血脂水平。其中复方芪麻胶囊高剂量组下降值最明显,各剂量组间比较,差异具有统计学意义(P<0.05),说明复方芪麻胶囊干预血脂的疗效存在着量效关系。
(8)大鼠腹主动脉病理检测结果分析：与健康组比较：空白组大鼠腹主动脉中膜结构、形态见明显改变,增厚明显,说明ISH动物模型复制成功。与硝苯地平组比较,中、高剂量组大动脉中膜结构、形态未见明显改变,中膜增厚不明显；低剂量组中膜纤维结构紊乱,形态不规则,动脉胶原蛋白明显增多,说明复方芪麻胶囊能有效改善ISH大鼠硬化的腹主动脉,起到一定的靶器官保护作用,且改善动脉硬化的程度呈剂量依赖性。
4.结论
(1)复方芪麻胶囊不仅能有效降低ISH大鼠体内的Hcy水平,且其降低血Hey水平与复方芪麻胶囊呈效量关系。
(2)复方芪麻胶囊能明显降低ISH大鼠的收缩压,对舒张压影响较小,但降压疗效存在着效量关系。
(3)复方芪麻胶囊能显著降低ISH大鼠血清中TC、TG、LDL-C、LP(a)水平,且其疗效存在着量效关系。。
(4)复方芪麻胶囊能有效减轻ISH大鼠腹主动脉的硬化程度,且其疗效与剂量呈依赖性。
三、临床研究
1.目的
观察复方芪麻胶囊对单纯收缩期高血压患者的临床疗效。
2.方法与内容
采用前瞻性实验性设计方案。遵循随机、对照、单盲原则进行研究。将60例符合中医气虚痰浊型诊断和西医单纯收缩期高血压1、2级标准的患者按1：1随机分为实验组和对照组。治疗组采用复方芪麻胶囊治疗,对照组采用硝苯地平缓释片治疗。通过观察治疗前后血压的变化及中医证候、症状的改变,比较实验组与对照组二者的临床疗效。
3.结果
(1)治疗后两组患者降压疗效的比较：对照组降压总有效率为86.7%,治疗组降压总有效率为93.3%,两组差异无统计学意义(P>0.05),说明两组患者的降压疗效相当。
(2)两组患者治疗前后24h动态血压结果的比较：治疗组与对照组治疗前后24h动态血压自身比较,经t检验,P<0.05,差异有统计学意义,说明复方芪麻胶囊与硝苯地平缓释片均能有效降低血压。两组患者治疗后24h动态血压比较,经t检验,P>0.05,差异无统计学意义,说明复方芪麻胶囊降压疗效与硝苯地平缓释片相当。治疗后两组平滑指数比较,治疗组明显高于对照组,差异有统计学意义(P<0.05),说明复方芪麻胶囊降压作用较硝苯地平缓释片平稳。
(3)两组患者中医证候疗效比较：治疗组总有效率93.3%,对照组73.3%,经X2检验P<0.05,差异有统计学意义。
(4)两组患者中医症状积分比较：治疗前后自身比较,差异有统计学意义(P<0.05)。治疗组患者治疗前后症状积分差值明显高于对照组,经t检验,P<0.05,差异有统计学意义。
(5)两组患者中医症状疗效比较：治疗组眩晕症状总有效率为83.3%,对照组总有效率为50%,两组差异有统计学意义(P<0,05)；治疗组头重症状总有效率为80.8%,对照组总有效率为47.8%,两组差异有统计学意义(P<0,05)；治疗组神疲乏力症状总有效率为89.7%,对照组为60.0%,两组差异有统计学意义(P<0,05)；余各中医症状疗效差异无统计学意义(P>0.05)。
4。结论
我们通过小样本临床观察,发现复方芪麻胶囊能有效降低1、2级ISH患者的收缩压,对舒张压影响较小,其降压疗效与硝苯地平缓释片相当,同时能明确改善ISH患者血压平滑指数,降压作用较硝苯地平缓释片平稳。其次复方芪麻胶囊在改善气虚痰浊证患者中医证候及中医症状方面疗效优于单纯西药治疗,而且其副作用较少。
四、结语
1.复方芪麻胶囊能有效降低ISH大鼠体内的Hcy水平,且其降低血Hcy水平与复方芪麻胶囊呈效量关系。
2.复方芪麻胶囊能有效降低ISH大鼠收缩压,对舒张压影响较小,但降压疗效存在着量效关系。
3.复方芪麻胶囊能有效降低ISH大鼠血TG、TC、LDL-C、LP(a)水平,且其干预疗效存在着量效关系。
4.复方芪麻胶囊能有效减轻ISH大鼠腹主动脉的硬化程度,且其疗效与剂量呈依赖性。
5.我们通过小样本临床观察,发现复方芪麻胶囊能有效降低1、2级ISH患者的收缩压,对舒张压影响较小,其降压疗效与硝苯地平缓释片相当,同时能明确改善ISH患者血压平滑指数,降压作用较硝苯地平缓释片平稳。其次复方芪麻胶囊在改善气虚痰浊证患者中医证候及中医症状方面疗效优于单纯西药治疗,而且其副作用较少。
Today, isolated systolic hypertension has become one of the main diseases of threaten the human health. Along with our country old population quantity's increase, the ISH disease incidence rate also assumes gradually the trend of escalation in our country. Now some researchs had confirm that ISH is the most common hypertension hypotype in the old age crowd, occupies old age hypertension crowd more than half. Simultaneously ISH is one of senior citizen's important cardiovascular hazard factors, its and cardiovascular disease's formation rate and the case fatality rate present are related, his/her the cardiovascular complication's disease incidence rate and the case fatality rate are blood pressure normal person's 3 times, and the early kidney function harm relations are close. Although the humanity has spent the massive manpower, the financial resource research to treat ISH the effective medicine, but so far it has the inevitable side effect. Therefore began from the Chinese medicine aspect, to seek treats ISH the effective medicine already to become hypertension to prevent and control the domain an important domain. At present up to, although there already had many reports to traditional Chinese medicine preparation applied to reat ISH,but related treats ISH the compound prescription prepared medicine and closes with these traditional Chinese medicine preparation treats ISH the mechanism research not to see the report, this topic is the plan makes a beneficial exploration in this domain.
This research institute uses the preparation Compound Qima Capsules(CQC)is Invented by Professor Wang Qinghai,who based on the Chinese medicine basic theory, summarizes the Chinese medicine dialectical minute which earnestly modern hypertension gets sick, unifies oneself dozens of years to practice medicine the experience to develop after the proven prescription. Many years'clinical practice has confirm that Compound Qima Capsules can descense hypertension Effectively, especially has the accurate curative effect to old ages who with isolated systolic hypertension. But until present there is not any research about the mechanism of Compound Qima Capsules treating isolated systolic hypertension. this study was a beneficial evaluation in this field. Experiment Study
OBJECTIVE:To observe the effect of Compound Qima Capsules(CQC)for the level of Hcy、TC、TG、LDL-C、LP(a) of rice with isolated systolic hypertension(ISH), to evaluate the mechanism of Compound Qima Capsules(CQC) to treatment of ISH by using the experimental model of rats.
METHODS:SD rats were randomized into six group:healthy group, blank group, control group, high dose、moderate and low dose group. To establish rats model with the model of WVK, with the medols such as the electron microscopic cytochemistry of enzyme, molecular biologic technique and immunohistochemical technique, to evaluate the mechanism of Compound Qima Capsules (CQC) to treatment of ISH. This study includes 3 parts. Part 1:To observe the effect of Compound Qima Capsules (CQC) for the level Hcy to evaluate the he mechanism of Compound Qima Capsules(CQC) to treatment of ISH. Part 2:observation on the effect of Compound Qima Capsules(CQC) on the blood pressure and blood fats, to evaluate the mechanism of decending blood pressure and improves the degre of arteriosclerosis. Part3:by pothology to observe the effect of Compound Qima Capsules(CQC) modifies the degree of arteriosclerosis of mouse, To offer experimental evidence about CQC treat ISH.
RESULTS:
(1) Comparion about the blood between pre-model and post-model model: compare to the healthy group, the systolic blood pressure level of model groups were markedly increased from the third week, there were significant differences between the two groups(P<0.05); while there was no significant differences between the diastolic pressure. A design of oneself comparion according to pre-model and post-model was performed in different dose groups. There was significant difference in systolic pressure in model group(P<0.05), while there was no significant difference in diastolic pressure. That means it is successful in copy model.
(2) Comparion between model group and healthy group:the blood Hey level of model group was markedly increased, there were significant difference s between the two groups(P<0.05), that means The blood Hey level and the ISH occurrence has the close relation.
(3) Comparison of the effect of decending blood Hey:the blood level of Hey reduce markedly in the low dose, moderate and high dose group. that means Compound Qima Capsules(CQC) can effectively reduce the level of blood Hey of rats with isolated systolic hypertension
(4) Compare to blank group, there was some reduce in the level of blood Hey after post-treatment, especially in high dose group, There were significant differences (P<0.01). that means Compound Qima Capsules (CQC) can reducing the level of blood Hey of ISH rats, while the effect is related to dose.
(5)Comparion of systolic pressure pre-treatment and post-treatment: compare to blank group, the systolic pressure of Nifedipine group reduced obviously in the first week, There were significant differences (P<0.01). While the the systolic pressure of CQC groups reduced markedly from the third week,there were significant differences only in model and high dose groups. After treating four weeks, there were no differences in systolic pressure between CQC high dose group and Nifedipine group, that means high dose of CQC has the same efficacy as Nifedipine Tablets in decreasing systolic pressure.Compare to blank group in the same time and pre-treat, systolic pressure has markedly reduced in different dose group, there were significant differences(P<0.05), while reduced most in high dose group (P<0.01). That means the effecy of CQC on decending systolic pressure is related to dose.
(6)Comparion of diatolic pressure between blank group and pre-
treatment:Compare to blank group in the same time and pre-treatment, diatolic pressure of Nifedipine group reduced markedly, there were significant differences (P<0.05). While there were no significant differences in CQC groups after treatment, compare to blank group in the same time and pre-treatment (P>0.05). That means CQC has little effect on diatlic pressure.
(7) Comparion of blood fats pre-treatment and post-treatment:the level of TC、TG、LDL-C、LP(a) increases markedly of the control groups compares to the blank groups, that means existent fat metabolic disorder in rats with isolated systolic hypertension. Compare to blank group, the level of blood TG、TC、LDL、LP(a) reduce obviously, there were significant differences, that means CQC can effectively interven level of blood fats of ISH rats. But it reduced most in the high dose group, comparion among different dose groups, there were significant differences, that means the effecy of CQC on decending blood fats level is related to dose.
(8) The pathology test result of rats'abdomen aorta:Compares with the healthy group:the blank group aorta tunica media vasorum structure, the shape see obvious change, the accumulation are obvious, showed that the ISH animal model duplicates successfully. Compares to the Nifedipine group, the medium and high dose group has not seen the obvious change, the tunica media vasorum accumulation are not obvious; The low dose group aorta tunica media vasorum structure, the shape see the obvious change, explained that the compound prescription qi hemp capsule improvement arteriosclerosis the degree and the dosage have the close relation.
CONCLUSION:
(1) The Compound Qima Capsules can reduce the level of blood Hey of rats with isolated systolic hypertension, and its effect is related to the quantity.
(2) The compound Qima Capsules can decend the systolic pressure obviously of rats with ISH, and has little influence on dialotid pressure, but the effect in reducing blood pressure has the effect quantity relations.
(3) The Compound Qima Capsules can reduce the level of blood fats of rats with isolated systolic hypertension, and the effect is related to the dose.
(4) CQC can effectively reduce the sclerosis degree of aortaventralis with ISH, and the effect is related to dose. Clinical Study
OBJECTIVE:To observe the clinic effect of Compound Qima Capsules (CQC) for the treatment of isolated systolic hypertension (ISH) with Qi deficiency and phlegm turbidity.
METHODS:A prospective study was done of Qi deficiency and phlegm turbidity in 60 patients with ISH under the randomized, controlled and single-blind rules. These patients were randomized into control and experimental groups in 1:1 proportion. These patients in experimental group received CQC; while the patients in control group received extended-release Nifedipine Tablets.To compare the clinic efficiency to the patients in control and experimental groups by observing the change of hypertension and the change of traditional Chinese medicine syndrome and symptom before and after treatment.
RESULTS:
(1) Comparion of the efficacy to blood pressure after treatment:the results of therapy were assessed as follows:the general effective rate being 86.7% in treatmental group, while 93.3% in control group, there was not significant differences between the two groups (P>0.05). It means that the two groups has same effect.
(2) Compare of the results of 24h ambulatory blood pressure:A design of oneself comparison according to pre-treatment and post-treatment was performed in both groups. There was significant differences in each group(P<0.05). The comparisons of 24h ambulatory blood pressure between two groups after treatment:there was not significant differences between the two groups(P>0.05). It illustrates that the two groups has same effect. The compariison in smoothness index between two groups after treatment:there was significant differences between two groups,that means the effect of CQC is moderater than Nifedipine Tablets.
(3) Compare of the efficacy to traditional Chinese medicine syndrome between control and experimental group:the general effective rate being 93.3% in treatmental group; the general effective rate being 73.3% in control group, there were significant differences between the two groups(P<0.05).
(4) Compare of the scores of traditional Chinese clinical symptoms between control and experimental group:A design of oneself comparison according to pre-treatment and post-treatment was performed in both groups. There were significant differences between pre-treatment and post-treatment in each group (P<0.05). The value between pre-treatment and post-treatment in experimental group had significant difference to that in control group(P<0.05).
(5) Compare of the traditional Chinese medicine symptom between control and experimental group:the general effective rate to god tired strength being 89.7% in experimental group, while 60.0% in control group. there were significant differences between the two groups (P<0,05). The general effective rate to head heaviness being 80.8% in experimental group, while 47.8% in control group. there were significant differences between the two groups(P<0,05). the genenral effective rate to dizziness being 83.3% in experimental group, while 50% in control group. there were significant differences between the two groups(P<0,05).There were no significant differences of other symptom between the two groups(P>0.05).
CONCLUSION:
Through the observation of treatment of Compound Qima Capsules for for the treatment of 1.2 leve isolated systolic hypetension(ISH)with Qi deficiency and phlegm turbidity, we found that CQC has the same efficacy as Nifedipine Tablets in decreasing blood pressure,and has litter influence in dialotic pressure. But the improvement of traditional Chinese medicine syndrome and symptom, specially god tired strength、head heaviness and dizziness, is significantly increased in experimental group tha in control group. we also found that Compound Qima Capsule has lower side effect, so as to has a good prospect of application and extension.
CONCLUDING:
(1) The Compound Qima Capsules can reduce the level of blood Hcy of rats with isolated systolic hypertension, and its effect is related to the quantity.
(2) The compound Qima Capsules can decend the systolic pressure obviously of rats with ISH, and has little influence on dialotid pressure,but the effect in reducing blood pressure has the effect quantity relations.
(3) The Compound Qima Capsules can reduce the level of blood fats of rats with isolated systolic hypertension, and the effect is related to the dose.
(4) CQC can effectively reduce the sclerosis degree of aortaventralis with ISH, and the effect is related to dose.
(5) Through the observation of treatment of Compound Qima Capsules for for the treatment of 1.2 leve isolated systolic hypetension(ISH)with Qi deficiency and phlegm turbidity, we found that CQC has the same efficacy as Nifedipine Tablets in decreasing blood pressure, and has litter influence in dialotic pressure. But the improvement of traditional Chinese medicine syndrome and symptom, specially god tired strength、head heaviness and dizziness, is significantly increased in experimental group tha in control group. we also found that Compound Qima Capsule has lower side effect, so as to has a good prospect of application and extension.
当今,单纯收缩期高血压(ISH)已经成为威胁人类健康的主要疾病之一,随着我国老年人口数量的不断增加,ISH的发病率在我国亦呈逐渐上升趋势。已有研究证实ISH是老年人群中最常见的高血压亚型,占老年高血压人群半数以上。同时ISH是老年人重要的心血管危险因素之一,其与心血管病的发生率和病死率呈正相关,其心血管并发症的发病率和病死率是血压正常者的3倍,且与早期肾功能损害关系密切。尽管人类已花费了大量人力、财力研究治疗ISH的有效药物,但至目前为止其均存在不可避免的副作用。因此从中医药方面着手,寻求出治疗ISH的有效药物已经成为高血压防治领域的一重要课题。目前为止,虽然已有很多报道治疗ISH的中药制剂,但有关治疗ISH的复方成药及关于这些中药制剂治疗ISH的机制研究未见报道,本课题即打算在此领域作些有益的探索。
本研究所用制剂复方芪麻胶囊是王清海教授基于中医基础理论,认真总结现代高血压病的中医辨证分型,结合自己数十载行医经验研制出的经验方。多年临床实践证实复方芪麻胶囊对于高血压,尤其是老年ISH有确切疗效。有研究证明复方芪麻胶囊能有效降低24h、白昼及夜间的血压,减轻血压负荷,对心、脑、肾等靶器官有保护作用。但究竟其通过何种机制起到治疗ISH的作用尚不明确,本课题拟通过临床观察评估复方芪麻胶囊治疗ISH的疗效及安全性,同时通过实验研究初步探讨复方芪麻胶囊治疗ISH的机制。
二、实验研究
1.目的
(1)观察复方芪麻胶囊对ISH大鼠血清中Hcy水平的干预情况,明确复方芪麻胶囊治疗ISH的机制；
(2)观察复方芪麻胶囊对实验大鼠血压及血脂相关指标的干预疗效,明确复方芪麻胶囊治疗ISH的机制;
(3)从病理学方面明确复方芪麻胶囊改善实验动物动脉硬化的程度,为复方芪麻胶囊治疗ISH提供实验依据。
2.方法与内容
采用SD大鼠,随机分为6组：健康对照组、空白组对照组、硝苯地平组、复方芪麻胶囊低剂量组、中剂量组和高剂量组。采用WVK模式建立大鼠单纯收缩期高血压模型,采用电镜酶细胞化学和分子生物学及免疫组化等方法,从整体、细胞乃至分子水平探讨复方芪麻胶囊治疗ISH的机制。本实验共分为三个部分。实验一：采用WVK模式制造大鼠单纯收缩期高血压模型,观察复方芪麻胶囊对ISH大鼠血清中Hcy水平的干预情况,明确复方芪麻胶囊治疗ISH的机制。实验二：观察复方芪麻胶囊对大鼠血压及血脂的干预疗效,明确其降压机制。实验三：从病理学角度观察复方芪麻胶囊改善ISH大鼠腹主动脉硬化的程度,探讨复方芪麻胶囊改善动脉粥样硬化的机制。
3.结果
(1)造模前后血压比较：造模组与健康组大鼠造模后同期收缩压比较,自第三周起,收缩压明显升高,经t检验,P<0.05,差异有统计学意义；造模组与健康组同期舒张压比较,经t检验,P>0.05,差异无统计学意义。造模组造模前后自身收缩压比较,经t检验,P<0.05,差异有统计学意义；造模前后自身舒张压比较,经t检验,P>0.05,差异无统计学意义,说明造模成功。
(2)造模后各组与健康组比较,Hcy水平存在着明显差异(P<0.05),说明ISH发生时,血Hcy水平升高。单纯收缩期高血压的发生与高同型半胱氨酸血症密切相关。
(3)治疗前后血Hey水平自身比较：低、中、高剂量组存在显著性差异(P<0.05)。说明复方芪麻胶囊能有效降低ISH大鼠血Hcy水平。
(4)治疗后与空白组比较：低、中、高剂量组大鼠血Hcy水平均有所下降,其中高剂量组下降最明显,存在显著性差异(P<0.01)。说明复方芪麻胶囊能有效降低ISH大鼠血Hcy水平,疗效呈剂量依赖性。
(5)治疗前后收缩压比较：与空白组同期比较,自第一周起硝苯地平组收缩压即见明显降低,经t检验,P<0.01,差异具有统计学意义,而复方芪麻胶囊各剂量组收缩压则自第三周起出现明显下降,中、高剂量组差异具有显著性(P<0.05),具有统计学意义。治疗后第四周,复方芪麻胶囊高剂量组与硝苯地平组血压比较,差异无统计学意义(P>0.05),说明复方芪麻胶囊高剂量降低收缩压疗效与硝苯地平片相当。与空白组同期及治疗前自身比较,复方芪麻胶囊低、中、高剂量组收缩压均明显下降,差异具有统计学意义(P<0.05),其中高剂量组血压下降最明显(P<0.01),说明复方芪麻胶囊降低收缩压的疗效存在着量效关系。
(6)治疗前后舒张压比较：与空白组同期和治疗前自身比较,硝苯地平组治疗后舒张压下降明显,经t检验,P<0.05,差异具有统计学意义。复方芪麻胶囊各剂量组治疗后舒张压,与空白组同期及治疗前自身比较,差异无统计学意义(P>0.05),说明复方芪麻胶囊对舒张压影响较小。
(7)治疗后各组大鼠血脂水平比较：空白组与健康组比较,TC、TG、LDL-C、LP(a)含量明显升高,存在显著性差异(P<0.05),说明ISH大鼠存在脂代谢紊乱。复方芪麻胶囊各剂量组与空白组比较,TG、TC、LDL、LP(a)含量均明显减低,存在显著性差异(P<0.05),说明复方芪麻胶囊能有效干预ISH大鼠血脂水平。其中复方芪麻胶囊高剂量组下降值最明显,各剂量组间比较,差异具有统计学意义(P<0.05),说明复方芪麻胶囊干预血脂的疗效存在着量效关系。
(8)大鼠腹主动脉病理检测结果分析：与健康组比较：空白组大鼠腹主动脉中膜结构、形态见明显改变,增厚明显,说明ISH动物模型复制成功。与硝苯地平组比较,中、高剂量组大动脉中膜结构、形态未见明显改变,中膜增厚不明显；低剂量组中膜纤维结构紊乱,形态不规则,动脉胶原蛋白明显增多,说明复方芪麻胶囊能有效改善ISH大鼠硬化的腹主动脉,起到一定的靶器官保护作用,且改善动脉硬化的程度呈剂量依赖性。
4.结论
(1)复方芪麻胶囊不仅能有效降低ISH大鼠体内的Hcy水平,且其降低血Hey水平与复方芪麻胶囊呈效量关系。
(2)复方芪麻胶囊能明显降低ISH大鼠的收缩压,对舒张压影响较小,但降压疗效存在着效量关系。
(3)复方芪麻胶囊能显著降低ISH大鼠血清中TC、TG、LDL-C、LP(a)水平,且其疗效存在着量效关系。。
(4)复方芪麻胶囊能有效减轻ISH大鼠腹主动脉的硬化程度,且其疗效与剂量呈依赖性。
三、临床研究
1.目的
观察复方芪麻胶囊对单纯收缩期高血压患者的临床疗效。
2.方法与内容
采用前瞻性实验性设计方案。遵循随机、对照、单盲原则进行研究。将60例符合中医气虚痰浊型诊断和西医单纯收缩期高血压1、2级标准的患者按1：1随机分为实验组和对照组。治疗组采用复方芪麻胶囊治疗,对照组采用硝苯地平缓释片治疗。通过观察治疗前后血压的变化及中医证候、症状的改变,比较实验组与对照组二者的临床疗效。
3.结果
(1)治疗后两组患者降压疗效的比较：对照组降压总有效率为86.7%,治疗组降压总有效率为93.3%,两组差异无统计学意义(P>0.05),说明两组患者的降压疗效相当。
(2)两组患者治疗前后24h动态血压结果的比较：治疗组与对照组治疗前后24h动态血压自身比较,经t检验,P<0.05,差异有统计学意义,说明复方芪麻胶囊与硝苯地平缓释片均能有效降低血压。两组患者治疗后24h动态血压比较,经t检验,P>0.05,差异无统计学意义,说明复方芪麻胶囊降压疗效与硝苯地平缓释片相当。治疗后两组平滑指数比较,治疗组明显高于对照组,差异有统计学意义(P<0.05),说明复方芪麻胶囊降压作用较硝苯地平缓释片平稳。
(3)两组患者中医证候疗效比较：治疗组总有效率93.3%,对照组73.3%,经X2检验P<0.05,差异有统计学意义。
(4)两组患者中医症状积分比较：治疗前后自身比较,差异有统计学意义(P<0.05)。治疗组患者治疗前后症状积分差值明显高于对照组,经t检验,P<0.05,差异有统计学意义。
(5)两组患者中医症状疗效比较：治疗组眩晕症状总有效率为83.3%,对照组总有效率为50%,两组差异有统计学意义(P<0,05)；治疗组头重症状总有效率为80.8%,对照组总有效率为47.8%,两组差异有统计学意义(P<0,05)；治疗组神疲乏力症状总有效率为89.7%,对照组为60.0%,两组差异有统计学意义(P<0,05)；余各中医症状疗效差异无统计学意义(P>0.05)。
4。结论
我们通过小样本临床观察,发现复方芪麻胶囊能有效降低1、2级ISH患者的收缩压,对舒张压影响较小,其降压疗效与硝苯地平缓释片相当,同时能明确改善ISH患者血压平滑指数,降压作用较硝苯地平缓释片平稳。其次复方芪麻胶囊在改善气虚痰浊证患者中医证候及中医症状方面疗效优于单纯西药治疗,而且其副作用较少。
四、结语
1.复方芪麻胶囊能有效降低ISH大鼠体内的Hcy水平,且其降低血Hcy水平与复方芪麻胶囊呈效量关系。
2.复方芪麻胶囊能有效降低ISH大鼠收缩压,对舒张压影响较小,但降压疗效存在着量效关系。
3.复方芪麻胶囊能有效降低ISH大鼠血TG、TC、LDL-C、LP(a)水平,且其干预疗效存在着量效关系。
4.复方芪麻胶囊能有效减轻ISH大鼠腹主动脉的硬化程度,且其疗效与剂量呈依赖性。
5.我们通过小样本临床观察,发现复方芪麻胶囊能有效降低1、2级ISH患者的收缩压,对舒张压影响较小,其降压疗效与硝苯地平缓释片相当,同时能明确改善ISH患者血压平滑指数,降压作用较硝苯地平缓释片平稳。其次复方芪麻胶囊在改善气虚痰浊证患者中医证候及中医症状方面疗效优于单纯西药治疗,而且其副作用较少。
Today, isolated systolic hypertension has become one of the main diseases of threaten the human health. Along with our country old population quantity's increase, the ISH disease incidence rate also assumes gradually the trend of escalation in our country. Now some researchs had confirm that ISH is the most common hypertension hypotype in the old age crowd, occupies old age hypertension crowd more than half. Simultaneously ISH is one of senior citizen's important cardiovascular hazard factors, its and cardiovascular disease's formation rate and the case fatality rate present are related, his/her the cardiovascular complication's disease incidence rate and the case fatality rate are blood pressure normal person's 3 times, and the early kidney function harm relations are close. Although the humanity has spent the massive manpower, the financial resource research to treat ISH the effective medicine, but so far it has the inevitable side effect. Therefore began from the Chinese medicine aspect, to seek treats ISH the effective medicine already to become hypertension to prevent and control the domain an important domain. At present up to, although there already had many reports to traditional Chinese medicine preparation applied to reat ISH,but related treats ISH the compound prescription prepared medicine and closes with these traditional Chinese medicine preparation treats ISH the mechanism research not to see the report, this topic is the plan makes a beneficial exploration in this domain.
This research institute uses the preparation Compound Qima Capsules(CQC)is Invented by Professor Wang Qinghai,who based on the Chinese medicine basic theory, summarizes the Chinese medicine dialectical minute which earnestly modern hypertension gets sick, unifies oneself dozens of years to practice medicine the experience to develop after the proven prescription. Many years'clinical practice has confirm that Compound Qima Capsules can descense hypertension Effectively, especially has the accurate curative effect to old ages who with isolated systolic hypertension. But until present there is not any research about the mechanism of Compound Qima Capsules treating isolated systolic hypertension. this study was a beneficial evaluation in this field. Experiment Study
OBJECTIVE:To observe the effect of Compound Qima Capsules(CQC)for the level of Hcy、TC、TG、LDL-C、LP(a) of rice with isolated systolic hypertension(ISH), to evaluate the mechanism of Compound Qima Capsules(CQC) to treatment of ISH by using the experimental model of rats.
METHODS:SD rats were randomized into six group:healthy group, blank group, control group, high dose、moderate and low dose group. To establish rats model with the model of WVK, with the medols such as the electron microscopic cytochemistry of enzyme, molecular biologic technique and immunohistochemical technique, to evaluate the mechanism of Compound Qima Capsules (CQC) to treatment of ISH. This study includes 3 parts. Part 1:To observe the effect of Compound Qima Capsules (CQC) for the level Hcy to evaluate the he mechanism of Compound Qima Capsules(CQC) to treatment of ISH. Part 2:observation on the effect of Compound Qima Capsules(CQC) on the blood pressure and blood fats, to evaluate the mechanism of decending blood pressure and improves the degre of arteriosclerosis. Part3:by pothology to observe the effect of Compound Qima Capsules(CQC) modifies the degree of arteriosclerosis of mouse, To offer experimental evidence about CQC treat ISH.
RESULTS:
(1) Comparion about the blood between pre-model and post-model model: compare to the healthy group, the systolic blood pressure level of model groups were markedly increased from the third week, there were significant differences between the two groups(P<0.05); while there was no significant differences between the diastolic pressure. A design of oneself comparion according to pre-model and post-model was performed in different dose groups. There was significant difference in systolic pressure in model group(P<0.05), while there was no significant difference in diastolic pressure. That means it is successful in copy model.
(2) Comparion between model group and healthy group:the blood Hey level of model group was markedly increased, there were significant difference s between the two groups(P<0.05), that means The blood Hey level and the ISH occurrence has the close relation.
(3) Comparison of the effect of decending blood Hey:the blood level of Hey reduce markedly in the low dose, moderate and high dose group. that means Compound Qima Capsules(CQC) can effectively reduce the level of blood Hey of rats with isolated systolic hypertension
(4) Compare to blank group, there was some reduce in the level of blood Hey after post-treatment, especially in high dose group, There were significant differences (P<0.01). that means Compound Qima Capsules (CQC) can reducing the level of blood Hey of ISH rats, while the effect is related to dose.
(5)Comparion of systolic pressure pre-treatment and post-treatment: compare to blank group, the systolic pressure of Nifedipine group reduced obviously in the first week, There were significant differences (P<0.01). While the the systolic pressure of CQC groups reduced markedly from the third week,there were significant differences only in model and high dose groups. After treating four weeks, there were no differences in systolic pressure between CQC high dose group and Nifedipine group, that means high dose of CQC has the same efficacy as Nifedipine Tablets in decreasing systolic pressure.Compare to blank group in the same time and pre-treat, systolic pressure has markedly reduced in different dose group, there were significant differences(P<0.05), while reduced most in high dose group (P<0.01). That means the effecy of CQC on decending systolic pressure is related to dose.
(6)Comparion of diatolic pressure between blank group and pre-
treatment:Compare to blank group in the same time and pre-treatment, diatolic pressure of Nifedipine group reduced markedly, there were significant differences (P<0.05). While there were no significant differences in CQC groups after treatment, compare to blank group in the same time and pre-treatment (P>0.05). That means CQC has little effect on diatlic pressure.
(7) Comparion of blood fats pre-treatment and post-treatment:the level of TC、TG、LDL-C、LP(a) increases markedly of the control groups compares to the blank groups, that means existent fat metabolic disorder in rats with isolated systolic hypertension. Compare to blank group, the level of blood TG、TC、LDL、LP(a) reduce obviously, there were significant differences, that means CQC can effectively interven level of blood fats of ISH rats. But it reduced most in the high dose group, comparion among different dose groups, there were significant differences, that means the effecy of CQC on decending blood fats level is related to dose.
(8) The pathology test result of rats'abdomen aorta:Compares with the healthy group:the blank group aorta tunica media vasorum structure, the shape see obvious change, the accumulation are obvious, showed that the ISH animal model duplicates successfully. Compares to the Nifedipine group, the medium and high dose group has not seen the obvious change, the tunica media vasorum accumulation are not obvious; The low dose group aorta tunica media vasorum structure, the shape see the obvious change, explained that the compound prescription qi hemp capsule improvement arteriosclerosis the degree and the dosage have the close relation.
CONCLUSION:
(1) The Compound Qima Capsules can reduce the level of blood Hey of rats with isolated systolic hypertension, and its effect is related to the quantity.
(2) The compound Qima Capsules can decend the systolic pressure obviously of rats with ISH, and has little influence on dialotid pressure, but the effect in reducing blood pressure has the effect quantity relations.
(3) The Compound Qima Capsules can reduce the level of blood fats of rats with isolated systolic hypertension, and the effect is related to the dose.
(4) CQC can effectively reduce the sclerosis degree of aortaventralis with ISH, and the effect is related to dose. Clinical Study
OBJECTIVE:To observe the clinic effect of Compound Qima Capsules (CQC) for the treatment of isolated systolic hypertension (ISH) with Qi deficiency and phlegm turbidity.
METHODS:A prospective study was done of Qi deficiency and phlegm turbidity in 60 patients with ISH under the randomized, controlled and single-blind rules. These patients were randomized into control and experimental groups in 1:1 proportion. These patients in experimental group received CQC; while the patients in control group received extended-release Nifedipine Tablets.To compare the clinic efficiency to the patients in control and experimental groups by observing the change of hypertension and the change of traditional Chinese medicine syndrome and symptom before and after treatment.
RESULTS:
(1) Comparion of the efficacy to blood pressure after treatment:the results of therapy were assessed as follows:the general effective rate being 86.7% in treatmental group, while 93.3% in control group, there was not significant differences between the two groups (P>0.05). It means that the two groups has same effect.
(2) Compare of the results of 24h ambulatory blood pressure:A design of oneself comparison according to pre-treatment and post-treatment was performed in both groups. There was significant differences in each group(P<0.05). The comparisons of 24h ambulatory blood pressure between two groups after treatment:there was not significant differences between the two groups(P>0.05). It illustrates that the two groups has same effect. The compariison in smoothness index between two groups after treatment:there was significant differences between two groups,that means the effect of CQC is moderater than Nifedipine Tablets.
(3) Compare of the efficacy to traditional Chinese medicine syndrome between control and experimental group:the general effective rate being 93.3% in treatmental group; the general effective rate being 73.3% in control group, there were significant differences between the two groups(P<0.05).
(4) Compare of the scores of traditional Chinese clinical symptoms between control and experimental group:A design of oneself comparison according to pre-treatment and post-treatment was performed in both groups. There were significant differences between pre-treatment and post-treatment in each group (P<0.05). The value between pre-treatment and post-treatment in experimental group had significant difference to that in control group(P<0.05).
(5) Compare of the traditional Chinese medicine symptom between control and experimental group:the general effective rate to god tired strength being 89.7% in experimental group, while 60.0% in control group. there were significant differences between the two groups (P<0,05). The general effective rate to head heaviness being 80.8% in experimental group, while 47.8% in control group. there were significant differences between the two groups(P<0,05). the genenral effective rate to dizziness being 83.3% in experimental group, while 50% in control group. there were significant differences between the two groups(P<0,05).There were no significant differences of other symptom between the two groups(P>0.05).
CONCLUSION:
Through the observation of treatment of Compound Qima Capsules for for the treatment of 1.2 leve isolated systolic hypetension(ISH)with Qi deficiency and phlegm turbidity, we found that CQC has the same efficacy as Nifedipine Tablets in decreasing blood pressure,and has litter influence in dialotic pressure. But the improvement of traditional Chinese medicine syndrome and symptom, specially god tired strength、head heaviness and dizziness, is significantly increased in experimental group tha in control group. we also found that Compound Qima Capsule has lower side effect, so as to has a good prospect of application and extension.
CONCLUDING:
(1) The Compound Qima Capsules can reduce the level of blood Hcy of rats with isolated systolic hypertension, and its effect is related to the quantity.
(2) The compound Qima Capsules can decend the systolic pressure obviously of rats with ISH, and has little influence on dialotid pressure,but the effect in reducing blood pressure has the effect quantity relations.
(3) The Compound Qima Capsules can reduce the level of blood fats of rats with isolated systolic hypertension, and the effect is related to the dose.
(4) CQC can effectively reduce the sclerosis degree of aortaventralis with ISH, and the effect is related to dose.
(5) Through the observation of treatment of Compound Qima Capsules for for the treatment of 1.2 leve isolated systolic hypetension(ISH)with Qi deficiency and phlegm turbidity, we found that CQC has the same efficacy as Nifedipine Tablets in decreasing blood pressure, and has litter influence in dialotic pressure. But the improvement of traditional Chinese medicine syndrome and symptom, specially god tired strength、head heaviness and dizziness, is significantly increased in experimental group tha in control group. we also found that Compound Qima Capsule has lower side effect, so as to has a good prospect of application and extension.
引文
[1]孙宁玲.老年收缩期高血压的诊断及治疗.中国医师进修杂志,2006；29(1)：7-9.
[2]黄琳,王清海,李贵明,等.复方芪麻胶囊对气虚痰浊型高血压患者动态血压的影响.中国实验方剂学杂志,2004；10(5)：57-58.
[3]谭健苗,谭少文.血脂与动脉粥样硬化发展阶段的相关性.中国临床保健杂志.2007；10(4)：337-339.
[4]黄芸,戴闺柱,冯宗忱,等.高甘油三酯血症对血管内皮功能的影响.中华心血管病杂志,2003；31(6)：421-423.
[5]齐科研,黄慧,吕泽平,等.血脂异常与高血压的关联研究.中国老年保健医学.2009；7(1)：43-45.
[6]蒋萍,杨小红.低密度脂蛋白胆固醇、载脂蛋白B与颈动脉粥样硬化斑块的关系.江汉大学学报(医学版),2002；30(1)：28-30.
[7]Moon JY, Kwon HM, Kwon SW, et al. Lipoprotein(a) and LDL particle size are telated to the severity of coronary artery desease. Cardiology,2007; 108(4):282-289.
[8]Beatrix P, Florian T, Elisabeth K, et al. Homocysteine strongly enchances metal-catalyzed LDL oxidation in the p resence of cystine and cysteine [J]. therosclerosis,2003; 168 (1):39-48.
[9]王峥,高枫,郝洪军,等.缺血性脑血管病患者颈动脉斑块与TXB2、OxLDL、Lp(a)、Hcy相关性分析.中国神经精神疾病杂志,2008；34(11)：263-265.
[10]Mili Gupta, Priyanka Sharma, Gitanjali Garg. Plasma homocysteine:an independent or an interactive risk factor for coronary artery disease, Clinical Chimica Acta,2005; 352(1～2):121-125.
[11]秦宁,徐俊伟,苏楠,等.阿托伐他汀治疗血脂正常老年高血压临床观察.心脑血管病防治,2009；9(3)：205-207.
[12]崔淑娴,王立奎,陈杰.调脂治疗对老年收缩期高血压患者脉压的影响[J].中国医师进修杂志,2006；29(11)：63-64.
[13]Ji-Guang Wang, an A. Staessen. The benefit of treating isolated systolic hypertension. Current Hypertension Reperts,2001-7; 3(4).
[14]王立新.老年单纯收缩期高血压研究及治疗进展.中国老年学杂,2007；5(27)：1010-1011.
[15]陈新宇.论肝气虚在老年单纯收缩期高血压病中的表现.中国中医基础医学杂志,1999,5(4)：36.
[16]陆峰,杨传华,王震,等.补肾和络方对老年单纯收缩期高血压的疗效及其安全性评价.河南中医,2007；27(11)：31.
[17]沈丽.补肾益气、温阳利水法治疗老年单纯收缩期高血压病.中国医药学报,2002；17(9)：542.
[18]王劲红.张国伦教授运用益气活血法治疗老年高血压病经验.河北中医,2006；18(4)：247-248
[19]王清海,李桂明,李典鸿.高血压病中医证型分布规律的临床研究.新中医,2005；37(11)：26-27.
[20]MaliziaG, Dino 0, PisaR, et al. Expression of leukocyte adhesion mol eculesin the liver of patients with chronic hepatitis B virus infect ion. Gastroenterology,1991; 100(3):749-755.
[21]楼黎明,徐慧连,杨莉,等.高血压病患者血浆P-选择素、细胞间黏附分子-l的观察.浙江临床医学,2006；8(7)：746—747.
[22]李小兵,冼绍祥,洪永敦,等.高血压患者黏附分子水平异常与痰湿证关系的探讨.江苏中医药,2005；26(6)：15-16.
[23]金国健,樊锦秀,张茂华,等.老年高血压中医证候分型的黏附分子表达与血微循环的关系.浙江临床医学,2006;8(12)：1240-1241.
[24]Vaziri ND, Wang XQ, Oveisi F, et al. Induction of oxidative stress by glutathione depletion cause severe hypertension in normal rats. Hyp ertension,2000; 36(1):142.
[25]黄勇武,杨振汉,李文朗.生脉注射液对老年单纯收缩期高血压患者可溶性黏附分子水平的影响.检验医学与临床,2010；7(6)：1668.
[26]Pickering TG. Stress, inflammation, a nd hypertension. Jcin Hypertens, 2007; 9(7):567-571.
[27]Kim KI,Lee JH, Chang HJ, et al. Association between blood pressure v ariability and inflammatory marker in hypertensive pa-tients. Cite J,2008; 72(2):293-298.
[28]Naya M,Tsukamoto T, Morita K, et al. Plasma interleukin-6 and tumor n ecrosis factor-alpha can predict coronary end othelial dysfunction in h ypertensive patients.Hypertens Res,2007; 30(6):541-548.
[29]Zhang H, Park Y, Wu J, etal. Role of TNF-alpha in vascular dysfuncti on. Clin Sci,2009; 116(3):219-230.
[30]Chen L, Frister A, Wang S, et al. Interaction of vascular smooth musc le cells and monocytes by soluble factors synergis-tically enhances IL-6 and MCP-1 production. Am J Physiol Heart Circ Physiol,2009; 296(4):H987-996.
[31]陈建英,陈晓于,谢晓明,等.生脉注射液对老年单纯收缩期高血压患者TNF-a和IL-6水平的影响.中南药学,2009；7(8)：578-579.
[32]张运,孙肖文,赵云霞.通心络消退动脉粥样硬化斑机制的研究.中国医学论坛报,2004；30(23)：16.
[33]陶军.血管内皮功能心血管疾病治疗靶点.中国医学论坛报,2008；34(35)：C14.
[34]Huraux C, Makita T, Kurz S, et al. Sureroxide productions risk factors and endothelium-dependent relaxations in Human internal marmnary arterie. Circulation,1999; 99(1):53-59.
[35]吴以岭.络病学基础与临床研究,北京：中国科学技术出版社,2005,1：194-197.
[36]刘晶,张燕丽,王雅齐.复方丹参药理药效研究进展.2008,25(6)：23-24.
[37]天士力公司药物研究所.复方丹参滴丸对高脂血症的治疗作用.中国医学论坛报,2002；28(15)：5.
[38]曹铁生,段云有,扬炳昂,等.复方丹参滴丸对高脂血症和动脉粥样硬化的治疗作用-高分子辨率超声成像动态观察研究.中国医学论坛报,2003；29(36)：21.
[39]葛玉霞,段云有,阮骊韬,等.复方丹参滴丸对血管内皮功能的保护作用.中国临床康复,2004；8(6)：1069-1097.
[40]陈频,徐向进,史道华.复方丹参滴丸对胰岛素抵抗大鼠糖脂代谢的影响.中国医学论坛报,2008；34(42)：C8.
[41]温薇.丹参的药理作用及临床应用.中医药信息,2007；24(4)：54-55.
[42]黄美爱,陈晓龙,贾连旺,等.复方丹参滴丸对老年单纯收缩期高血血管内皮依赖性舒张功能的影响.中医药学报,2009；37(2)：32-33.
[43]魏茂提,王世鑫,李玉明,等.单纯收缩期高血压和双相高血压患者血NOS活性及MDA水平的变化.中国慢性病预防与控制,2001；9(4)：149-150.
[44]Tyttell KS,Bostom A, Selhub J, et al.High homocysteine levels&reind ependently related to isolated systolic hyperten-sionin older adults. Cir culation,1997; 96:1745-1749.
[45]曾春雨,刘光耀,王旭,等.老年人收缩期高血压血浆神经肽Y的改变及培哚普利干预的研究.中华老年医学杂志,1998；2(17)：17-18.
[46]Blundell G,Jones BG, Rose FA, et al. Homocysteine mediatd endotheial cell toxicity and its amelior ation. Atherosclerosis,1996; 1221:63.
[47]Lunberg JM, Tatemoto K. Pancreatic polypeptide family(APP, BPP, NPY and PYY)in relation to sympathetic vaso-constriction resistant to a-adre noceptor blockade. Acad Physiol Scand,1982; 116:392-402.
[48]李浩,宋春生,刘方州,等.老年高血压分型与健康老年人血浆同型半胱氨酸、神经肽Y及血脂水平的较研究.中国老年学杂志,2003；8(23)：496-498.
[49]Miller DW, Tessel RE. Age-dependent hyper-responsive pres-sot effects of intravenous neuropeptide Y(NPY):role of mode of peptide admi nistration and plasma NPY. like im. Munoreactivity. Cardiovasc Pharma col,1991; 18:647-651.
[50]李浩,刘芳,崔玲,等.降压胶囊治疗老年单纯收缩期高血压24例临床研究.中医杂志,2004；45(1)：26-28.
[51]李勇,罗心平,范维琥,等.麝香保心丸对动脉壁一氧化氮代谢的影响.中国急救医学,1999；19(8)：451-453.
[52]张奇志,卜培莉,于文强,等.麝香保心丸对自发性高血压大鼠心肌纤维化的干预研究.中西医结合心脑血管病杂志,2008；6(5)：546-548.
[53]Panza JA, Casino PR, Kilmyne CM, et al. Role of endotheli-um-derived ni tric oide ill in the abnomal endotheliurn-de-pendment vasorelaxation of patients with essential hypertension. Circulation,1993; 87:1468-1474.
[54]Kerr S, Brosnan MJ, Melntyre M, et al. superoxide anion production is increased in a model of genetic hypertension:the role of tire end othelium. Hypertens,1999; 33:1353-1358.
[55]谢钢,陈新宇.益气舒肝汤对单纯收缩期高血压病(肝气虚证)患者血浆GSH-PX、CAT的影响.中国现代医药,2005；4(6)：5-6.
[56]贾真,颐复生,通心络胶囊对血管内皮功能的影响.见：吴以岭主编.中医络病学说与心脑血管病-表方药通心络胶囊实验与临床研究.北京：中国科学技术出版社,2001,49：51.
[57]张丽华,刘余芳,何乓一.通心络胶囊治疗高血压80例的疗效.中国新药杂志,1998；7(增刊)：11-12.
[58]卫明,陈可冀.老年高血压病100例疗效观察.交通学报,1994；8(4)：425.
[59]吴晓斌.中医方药对老年高血压病的辨证论治.中国保健营养,2010；5(1)：318.
[60]张剑荣,陈红霞.运用中医经典理论辨证治疗高血压病.新疆中医药,2010；4(28)：93-94.
[61]李秀峰,张瑜珠.高血压病的病因病机、辨证论治及体会.中国医药指南,2009；7(4)：109.
[62]杨臻玉.高血压病辨证论治.新疆中医药,2007；25(4)：6-7.
[63]陈利群,海峰,王维谆.补肾化瘀法治疗老年单纯收缩期高血压60例的临床观.中国老年学杂,2005；10(25)：1236-1237.
[64]顾雄华.降气活血法治疗老年单纯性收缩期高血压36例.中西医结合心脑血管病杂志,2008；6(12)：1398-1399.
[65]虢沛,钱海凌,龚超奇.活血化瘀利水法联合西药治疗老年单纯收缩期高血压病 48例.广西中医药,2009；32(6)：33-34.
[66]李晓.益气化痰方治疗单纯收缩期高血压病47例.中国中医急症,2010；19(1)：124-125.
[67]李思宁,魏丹蕾.苓桂术甘汤治疗老年单纯收缩期高血压的疗效观察.湖北中医杂志,2007；29(7)：27-28.
[68]王子宽.程志清教授诊治中老年高血压病的临床经验[J].浙江中医学院学报,2004,28(1)：21-22.
[69]邹志东,齐放.滋肾温阳法治疗原发性高血压病31例分析.北京中医,2005；24(1)：43—45.
[70]潘力焘,李耀芳,金庆文.健脾平肝降压汤治疗高血压病的临床研究.深圳中西医结合杂志,2007；17(1)：22—24.
[71]田俊,邬渊敏,戴嫣.自拟补肾涤痰化瘀汤治疗高血压病临床观察.中西医结合心脑血管病杂志,2007；5(11)：1044-104.
[72]沈金玲,王守富.化痰平肝饮治疗高血压病60例临床观察.中国中医急症,2008；17(8)：1059—1060.
[73]周红梅.加味半夏白术天麻汤治疗痰湿壅盛型高血压病的临床观察.北京中医药,2008；27(5)：363—365.
[74]何欣,何立人.化湿泄浊方治疗高血压病临床观察.上海中医药杂志,2009；43(11)：36—38.
[75]王耀光.张伯礼教授辨证治疗心脑血管疾病临床用药经验撷拾.中医药通报,2006；5(2)：10—13.
[76]王勉,秦扬.加味血府逐瘀汤治疗高血压64例疗效观察.中国热带医学,2008；8(9)：1564—1595.
[77]孔丽君.补肾降压汤为主治疗老年单纯收缩期高血压32例.浙江中医杂志,2004；4：148-149.
[78]杨晓云.张民.平压止眩汤治疗单纯收缩期高血压48例.福建中医药.2006.37(3)：4-5.
[79]钟志明.滋潜汤治疗单纯收缩期高血压病45例.中国中医药科技,2006；13(2)：131.
[80]杨丁友,刘桂峰,吴兴利.黄芪陷胸胶囊治疗老年单纯收缩期高血压50例临床观察.中国动脉硬化杂志,2007；12(5)：137-140.
[81]王勉,秦扬,李冰.加味大补地黄汤治疗肝肾阴虚型高血压病103例临床分析.中国中药杂志,2008；33(18)：2144—2146.
[82]邹全林.尼群地平联合脑心通治疗老年单纯收缩期高血压临床疗效分析.中国现代药物应用,2009；3(20)：123-124.
[83]李香玉,吴新萍.复方丹参滴丸联合尼莫地平治疗老年单纯收缩期高血压临床疗效分析.中国实用医药,2009；4(3l)：133-134.
[84]郑秀英,陈俊琦.针药联合治疗老年单纯收缩期高血压的临床观察.现代中西医结合杂志,2010；19(19)：2366-2367.
[85]彭丽辉,冯玲媚.艾灸对高血压患者血压及N0、ET、SOD、MDA的影响.中国针灸.2004；24(3)：157—159.
[86]骆传江,徐华龙.中华推拿与西药治疗高血压各50例临床观察.按摩与导引,2002；17(1)：16—17.
[87]武炜,谢飞.生物反馈疗法治疗老年单纯收缩期高血压的临床疗效.中国医药导报,2008；5(29)：31.
[88]龚一萍,倪美文,宋宵红.天麻钩藤饮对高血压肝阳上亢证大鼠一氧化氮、内皮素干预作用的研究.中国中医药信息杂志,2004；11(2)：127-128.
[89]秦彩铃,刘群英,程志铭,等.钩藤、牛膝及二药伍用的实验研究.中国中药杂志,1994；19(6)：271-273.
[90]黄琳红,袁秉祥,贺建宇,等.珍菊降压片对肾性高血压大鼠血压的影响.西安交通大学学报(医学版),2003；24(6)：615-617.
[91]张笑丽,刘子旺.等首乌降压胶囊对肾性高血压大鼠血浆一氧化氮、内皮素水平的影响.光明中医,2005；20(1)：47-48.
[92]张瑛朝,张延敏.复方杜仲叶合剂对人体降压作用的实验研究.中成药,2001；23(6)：418-421.
[93]西北植物所.中草药通讯,1972；(4)：I2.
[94]田川智惠.罗布麻叶提取物的降压作用.KUGAKU ZASSHI,2004；124(11)：851～856.
[95]范维衡.杜仲叶和皮的药理作用研究.药学通报,1979；14(9)：404.
[96]秦振栋.药用植物研究论文选编,西安：西北大学生物系,1983：235.
[97]潘龙,支娟娟.杜仲糖苷对肾性高血压大鼠血压及血浆ET、N0的影响.现代中医药,2010；3(2)：54-56.
[98]吕俊华,杨文豪,熊爱华,等.红丝线草提取物对肾陛高血压模型大鼠降压机制研究.山东中医杂志,2004；23(6)：357-358.
[99]宋纯清,樊懿,黄伟晖,等.钩藤中不同成分降压作用的差异.中草药,2000；31(10)：762-764.
[100]余文海.钩藤对自发性高血压大鼠内皮的影响[J].国外医学·中医中药分册,2000；22(6)：351-352.
[101]怡悦.钩藤对自发性高血压大鼠血管内皮功能的影响.国外医学·中医中药分册,2000；22(1)：28-29.
[102]余俊先,吴芹.异钩藤碱对猫的心血管作用与血药浓度的关系.中国药理学与毒理学杂志,2002；16(3)：191-194.
[103]Shi JS.Wu Q. Liu GX. Effects(If isorhynchophlline on isolated rabbit aortic strip[J]. Acta Acad Med Zunyi(遵义医学院学报),1990；13(4)：16-19.
[104]Zhu Y, Liu GX, Huang XN. Negatively chronotropic and inotropic effects of rhynehophyline and isorhynehophylline on isolated guinea pig atria. Chin Pharmacol Toxicol(中国药理与毒理学杂志),1993；7(2)：117-121.
[105]缪化春,沈业寿.天麻多糖的降血压作用.高血压杂志,2006；7(14)：531.
[106]张梦娟.天麻多糖的提取、纯化和活性研究.北农林科技大学,2007；4(3)：45.
[107]孙中吉,王辉.天麻素注射液的药理作用和临床应用.时珍国医国药,2008；19(4)：1011-1013.
[108]毛跟年,张嫱,聂萌,等.天麻制剂对家兔血压的影响.陕西科技大学学报,2003；21(4)：50-54.
[109]何晓燕,赵淑梅,官汝淳.夏枯草对家兔降压作用机理的研究.通化师范学院学报,2002；23(5)：100.
[110]刘菊秀,苗戊,狄俊英,等.决明子降压作用的实验研究.天津中医,1990；6(5)：37—38.
[111]宋雪鹏,陈平平,柴象柩.葛根素对自发性高血压大鼠的降压作用及其对血浆肾素活性的影响.中国药理学报,1988；9(1)：52.
[112]陈沪生,王培仁,邵建华,等.葛根素的降压效果及其机理的研究.山东医科大学学报,1987；25(3)：28.
[113]黄兆铨,叶武.葛根素对高血压患者血浆内皮素和一氧化氮的影响.中国现代应用药学杂志,1999；16(3)：13.
[114]程能能,马越呜.地龙中降太的类血小板活化因子物质.中国中药杂志,1993；18(12)：747.
[115]李淑兰,谢桂芹,曲竞南,等.地龙降压作用的研究.中医药信息,1995；3：11.
[116]徐天予.全蝎的药理作用及临床新用.中国民族民间医药,2010；29(2)：29-30.
[117]于培明,田智勇,许启泰,等.辛夷研究的新进展.时珍国医国药,2005；16(7)：652-653.
[118]张洪平,李亚娟,章丹丹,等.辛夷二氯甲烷提取物对离体大鼠胸主动脉环的舒张作用及其机制.中国病理生理杂志,2010；26(9)：1689—1694.
[119]陈乐生,寄生药理研究.陕西中医,2000；21(Ⅱ)：520-521.
[120]晏莉.大蒜素药理作用和作用机理的探讨.实用临床医学,2008；9(1)：134-135.
[121]王立新.老年单纯收缩期高血压研究及治疗进展.中国老年学杂志,2007；27(10)：1010-1011.
[122]Ciufetti G, Schillaci G, Lo mbardini R, et al. Plasma viscosity in isolated systolic hypertension:the role of pulse pressure. Am J Hypertens,2005; 18(7):1005-1008.
[123]Kannel WB. Historic perspectives on the relative contributions of diastolic and systolic blood pressure elevation to cardiovascular risk profile. Am Heart J,1999; 138:205-210.
[124]何莉,曾朝荣.单纯收缩期高血压.中华高血压杂志,2007；15(11)：961.
[125]Strandberg TE, Salomaa YY, Vanhanen HT, et al. Isolated diastolic h ypertension, pulse pressure, and mean arterial pressure as predictors o f mortality during a follow-up of up to 32 years. J Hypertens,2002; 20(3):399-404.
[126]Aronson S,Boisvert D, Lapp W. Isolated systolic hypertension is as sociated with adverse outcomes from coronary artery bypass grafting surgery. Anesth Analg,2002; 94(5):1079-1084.
[127]Staessen JA, Gasowski J, Wang JG, et al. Risks of untreated and treat ed isolated systolic hypertension in the elderly:meta-analysis of outcome trials. Lancet,2000; 355(9207):865-872.
[128]陆再英,钟南山.内科学,北京：人民卫生出版社,2009,第7版：251-252.
[129]陈维清,吴系科.老年单纯收缩期高血压的病因探讨：病例对照研究.安徽医科大学学报,1992；27(2)：91-94.
[130]赵树柚摘译.国外医学老年医学分册,1989；9(2)：83.
[131]Dyer AR et al.J Chroa Dis.1982; 35:259.
[132]Dyer AR et al.J Chron Dis.1982; 35:275.
[133]Mecclellan W et al.Prev Med,1987; 16:686.
[134]Kannel WB et al. In Buljitt CJ ed. Epidemiology of Arterial Blood Pressur.Hugue:Martinus Ni jhoff,1980:256.
[135]Colandrea MA et al. Circulation,1970,41:239.
[136]张明华.单纯收缩期高血压的特点及治疗研究进展.中华临床医药,2004：5(10)：57-60.
[137]Fagard R H. Epidemiology of hypeertension in the elderly.Am J Geriatr Cardiol,2002; 11(1):23-28.
[138]Bog-Hansen E. Impaired glucose metabolism and obesity in Swedish patients with borderline isolated systolic hypertension:Skaraborg Hypertension and Diabetes Project. Diabetes Obes Metab,2001; 3(1):25-31.
[139]Martins D, Nelson K, Pan D, et al. The effect of gender on age-related blood pressure changes and the prevalence of isolated systolic hypertension among older adults:data from NHANES Ⅲ. J Gend Specif Med,2001; 4(3): 10-20.
[140]Banega JR, de-la-Cruz JJ, Rodriguez-ArtalejoF,et al. Systolic vs diastolic blood pressure:community burden and impact on blood pressure staging. J Hum Hypertens,2002; 16(3):163-167.
[141]Yeh CJ, Pan WH, Jong YS, et al. Incidence and predictors of isolated systolic hypertension and isolated diastolic hypertension in Taiwan. J Formos Med Assoc,2001; 100(10):668-675.
[142]Manfredini R, Boari B, Portaluppi F. Morning surge in blood pressure as a predictor of silent and clinical cerebrovascuLar disease in elderly hypertensives.Circulation,2003; 108(10):e72-e73.
[143]Glynn RJ, Chae CU, Guralnik JM, et al. Pulse pressure and mortality in order people.Arch intern Med,2000; 160:2765-72.
[144]黄玫,李晓天,王丹丹.老年单纯收缩期高血压的危险因素与药物治疗.中国老年学杂志,2008：28(24)：2503-2505.
[145]Kannel WB. Historic perspectives on the relative contributions of diastolic and systolic blood pressure elevation to cardiovascular risk profile.Am Heart J,1999; 138:205-210.
[146]Safar ME. Systolic blood pressure,pulse pressure and arterial stifness as cardiovascular risk facters. Curt Opin Nephrol Hypertens,2001; 10(2):257-61.
[147]KawasakiT,SasayamaS, YagiS, et al.Non invasive assessment of the age related changes in stiffness of major branches of the human arteries. CardiovascRes,1987; 21 (9):.678-87.
[148]AvolioAP, ChertSG, WangRP, etal. Effectsof agingon changing arterial compliance and left ventricular load in a northern Chinese urban community.Circulation,1983; 68(1):50-58.
[149]Rourke MF. Arterial stiffness, systolic blood pressure and lngi caltreatment of arterial hypertension. Hypertension,1990; 15:45.
[150]马淑平,王国华,计承.老年单纯收缩期高血压问题的再探讨.河北医药,2004；26(10)：817.
[151]Vasari RS, Beiser A, Seshadri S, et al. Residual liffetime risk for de-veloping hypertension in middle-aged woman and man. JAMA,2002; 287(8):1003-1010.
[152]谭静,华琦,闻静,等.老年单纯收缩期高血压患者动脉僵硬度的临床研究.中华老年多器官疾病杂志,2007；6(6)：396-398.
[153]陈雯,郭进,王风,等.老年冠心病合并高血压患者血管内皮功能的改变.中国老年学杂志,2005；25(11)：1353—5.
[154]何莉,曾朝荣.单纯收缩期高血压.中华高血压杂志,2007；15(11)：961-962.
[155]李芳,姚丽霞,苑晓烨,等.老年高血压患者凌晨血压增高与血管内皮功能的相关性研究.山东医药,2010；50(33)：53-54.
[156]叶琳.内皮功能障碍及治疗对策.心血管病学进展,2000；21：245-248.
[157]李浩,蔡琳琳.老年单纯收缩期高血压诊治的若干问题探讨.世界中西医结合杂志,2009；4(11)：828-831.
[158]潘宏伟,周胜华,等.单纯收缩期高血压患者的心率震荡与心率变异.临床心血管病杂志[J].2007,23(10)：728-730.
[159]邓烈华,黄榕,邬真力,等.单纯收缩期高血压患者脉搏波传导速度与心率变异性.中华高血压杂志,2008；16(11)：987-990.
[160]陆再英,钟南山.内科学,北京：人民卫生出版社,2009,第7版：253.
[161]Dendorfer A, Dominiak P, Schunkert H. ACE inhibi-tors and angiotensin Ⅱ receptor antagonists. Handb Exp Pharmacol,2005; 170:407-442.
[162]Irita J, Okura T, Manabe S, et al. Plasma osteopontin levels are higher in patients with primary aldosteronism than in patients with essential hypertension.Am J Hy-pertens,2006; 19(3):293-299.
[163]孙海燕.肾素-血管紧张素系统在高血压发病机制及药物治疗中的作用.深圳职业技术学院学报,2005；2(4)：43-47.
[164]孙晓方,肖新华.ARB降压机制及降压外的作用.药品评价,2009；6(4)：129-131.
[165]中华医学会糖尿病学分会代谢综合征研究协作组.中华医学会糖尿病学分会关于代谢综合征的建议.中华糖尿病杂志,2004；12(3)：156—161.
[166]Sarzani R, Salvi F,Dessl-Fulgheri P, et al. Renin-angiotensin sys-tem, Natriuretic peptides, obesity, metabolic syndrome, and hyper-tension:an Integrated view in humans. J Hypertens,2008; 26(5):831-843.
[167]Defronzo RA, Kashyap SR. The insulin resistance syndrome:physi-ological considerations.J Hypertens,2008; 26(5):831-843.
[168]翁春艳,江凤林,袁洪.胰岛素抵抗性高血压病的发病机制与治疗.医学综述,2009；15(4)：569-571.
[169]Potenza MA, Marasciulo FL, Chieppa DM, et al. insulin resistance in spontaneously hypertensive rats in associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production.AM J Physiol Heart Circ Physiol,2005; 289(2):813-822.
[170]Schillaci G, Pirro M, Gemelli F, et al.Increased C-reactive protein concentrations in never-treated hypertension:the role of systolic and pulse pressures. Hypertens,2003; 21:1841-1846.
[171]Sesso HD, Buring J E, Rifai N, Blake GJ, et al. C-reactive protein and the risk of developing hypertension.JAMA,2003; 290:2945-2951.
[172]Hayaishi-Okano R, Yamaaki Y, Katakami N, et al. Elevated C-reactive protein associates with early-stage carotid atheosclero-sis in young subjects with type diabetes.Diabetes Care,2002; 25:1432-1438.
[173]Fichtlscherer S, Rosenberer G, Disk H, et al. Elevated C-reactive protein levels and impaired endothelial vasoreactivity in pa-tients with coronary artery disease. Circulation,2002; 102:1000-1006.
[174]陈丽,高兴玉,张俊,等.老年高血压肱动脉内皮功能、颈动脉粥样硬化与血清肿瘤坏死因子α、白介素6关系的研究.四川医学,2005；26(5)：511-513.
[175]黎镇垣,马中富,甄慰毅,等.动态观察高血压患者血清白细胞介素18改变的临床意义.标记免疫分析与临床,2003；10：1-3.
[176]罗文利,李南方,柳达.老年单纯收缩期高血压与部分炎症因子的相关性分析.Chinese General Practice,2010; 13(9):3079-3080.
[177]刘建交,季光,等.药理实验方法学[J].2003.190—195.
[178]Martin Liebetrau, Dorothe Burggraf, Nathalie Wunderlich,et al. Hamann ACE inhibitation reduces activity of the plaminogen plasmin and MMP systems in the brain of spontaneous hypertensive stroke-prone rats. Neuroscience Letters,2005; 376:205-209.
[179]Alan R. Olzinskia, Tara A. McCaffertyb. Shufang Q, Zhaoc,etal. Hypertensive target organ damage is attenuated by a p38 MAPK inhibitor; Role of systemic blood pressure and endotheilal protection. Cardiovascular Research,2005; 66:170-178.
[180]周颖,陈虹,王明远,等.高血压动物模型研究进展.中国现代实用医学杂,2006；5(1)：51.
[181]Abdi A, Johns EJ. Importance of the rennin angiotensin system in he genetation of kedney failure in renovascular hypertension. J Hypertens, 1996; 14:1131-1137.
[182]Ramirez M, Pricto I, Martinez JM, et al. Renal a inopepti dase activities in animal models of hypertension. Cardiovascular Research,2007; 45: 176-178.
[183]Mercedes Losadaa, Sonia H, Torresb, et al.Amparo Sos Muscle arteriolar and venular reactivity in two models of hypertensive rats. Microvascular Research,2005; 69:142-148.
[184]Leenen FH, de Jong W. A solid silver clip for induction of predictavle levels of renal hypertension in the rate. J Appl physiol,1971; 31: 142-144.
[185]Fuji J, Kurihar H, Yamaguchi H, et al. A persistent hyperten-sion due to unilateral renal artery constriction in the rabbit. Jpn Circ J,196731: 1197-2000.
[186]Anderson WP, Ramsey DE,Takata M. development of hyper-tension from unilateral renal artery stenosis in conscious dogs. Hypertension, 1990; 16:441-451.
[187]Panek RL, Ryan MJ, Weishaar RE, et al. Development of a high renin model of hypertension in the cynomolgus monkey.Clin Exp Hypertens A,1991; 13:1395-1414.
[188]Leene FH, de Jong W. Plasma renin and sodium balance during development of moderate and sever renal hypertension in rats. Circ Res,1975; 36: S179-186.
[189]王立文,刘光耀.左侧植入路二肾一夹法复制肾血管性高血压大鼠动物模型.第三军医大学学报,1998；20(5)：394-395.
[190]杨宁,胡立斌,张中,等.肾血管性高血压动物模型建立及指标监测.中华放射学杂志,2002；11(2)：117-119.
[191]曹珊珊,李瑞芳,等.肾性高血压大鼠模型制作的改良方法.河南科技大学学报(医学版).2010,28(3)：165-167.
[192]杨志华,盛文利,侯清华,等.双肾双夹肾血管性高血压模型的制作与术后管理.中国比较医学杂志,2005；15(2)：54-56.
[193]Hall JE, Kuo JJ, da Silva AA, et al. Obesity-associated hyper-tension and kidney disease. Curr Opin Nephrol Hypertens,2003; 12:195-200.
[194]周颖,陈虹,王明远,等.高血压动物模型研究进展.中国现代实用医学杂,2006；5 (1)：52.
[195]沈加林,陈克敏,许建荣,等.球囊固定动脉法延髓神经血管压迫建立高血压动物模型的实验研.中华放射学杂志,2002；36(9)：773—775.
[196]张晓华,李善泉,沈加林,等.原发性高血压犬模型的建立[J].上海第二医科大学学报,2003；23(5)：406-408.
[197]张艳荣,张连峰,杨志伟.高血压实验动物模型.中华高血压杂志,2008；16(3)：205-207.
[198]王秀卿,高贞,郭红,等.慢性应激性高血压动物模型的建立.白求恩军医学院学报,2003；1(4)：202—203.
[199]Mullins JJ, Peters J, Ganten D. Fulminant hypertension in trans-genic rats harbouring the mouse Ren-2 gene. Nature,1990; 334:541-544.
[200]Kim HS, Krege JH, Kluckman KD, et al. Genetic control of blood pressure and the angiotensinogen locus. Proc Natl Acad Sci USA,1995; 92:2735-2739.
[201]Sugiyama F, Haraoka S, Watanabe T, et al. Acceleration of ath-erosclerotic lesions in transgenic mice with hypertension by the activated renin-angiotensin system. Lab Invest,1997; 76: 835-842.
[202]Pitzalis MV, Sarzani R, Dessi-Fulgheri P, et al.Allelic variants of natriuretic peptide receptor genes are associated with familily history of hypertension and cardiovascular phenotype. J Hy-pertens ,2003; 21:1491-1496.
[203]Oliver PM,Fox JE, Kim R, et al. Hypertension, cardiac hyper-trophy, and sudden death in mice lacking natriuretic peptide re-cepter A.Proc Natl Acad Sci USA,1997; 94:14730-14735.
[204]Sugiyama F, Yagami K, Paigen B. Mouse models of blood press-ure regulation and hypertension. Curr Hypertens Rep,2001; 3:41-48.
[205]Yang Z, Sibley DR, Jose PA. D5 dopamine receptor knock out mice and hypertension.J Recept Signal Transduct Res,2004; 24:149-164.
[206]Kurihara Y, Kurihara H, Suzuki H, et al. Elevated blood pres-sure and craniofacial abnormalities in mice deficient in endothelin-1. Nature,1994; 368:703-710.
[207]Atkinson J, Poitevin P, Chinllon JM, et al. Vascular calcium over loadp reduced by vitaminD3 plus nicotine treatment diminishes arterial distensibility in rats. Am J Physionl,1994; 266:H540-H547.
[208]Essalihi R, Dao HH, Yamaguchi N, et al.A new model of i-solated systolic hypertension induced by chronic warfarin and vitamin Kl treatment. Am J Hypertens,2003; 16(2):103-110.
[209]Donnell CJ, Shea MK, Price PA, et al. Matrix gla protein is associated with risk factors for atherosclerosis but not with coronary artery calcification. Arterioscler Thromb Vasc Bi-ol,2006; 26(12):2769-2774.
[210]刘承云,万晶晶,杨群芳,等.阿托伐他汀对华法林致大鼠主动脉中膜钙化及收缩压升高的影响.中国医院药学杂志,2008；28(21)：1733-1736.
[211]陈宁,吕圭源,陈素红.抗高血压新药及血灵降压机制研究进展.中国现代药物应用,2010；4(2)：85-87.
[212]YUNKER A M. Modulation and pharmacology of low voltag e-ac-tivated (T-Type) calcium channels. J Bioenerg Biomembr,2003; 35(6):557-598.
[213]曾春雨,刘光耀.脑内神经肽Y受体亚型与抗高血压药物的研究进展.国外医学药学分册,1997；24(2)：88-92.
[214]王俊敏.抗高血压药物的研究进展.医药论坛杂志,2005；26(1)：77-78.
[215]李兴凯,陈雅琴.复方抗高血压药物的研究应用及发展前景.实用药物与临床,2005；(8)：43-44.
[216]Essalihi IL Dao HH, Yamaguchi N, et al.A new model of isolated systolic hypertension induced by chronic warfarin and vitamin k1 treatment. Am J Hypertens,2003; 16:103-110.
[217]薛洁,谢梅林.中药血清药理学的方法研究近况.中草药,2003；34(6)：附9-11.
[218]李仪奎.中药血清药理学实验方法的若干问题.中药新药与临床药理,1999；10(2)：95-98.
[219]冯淑芝,张佚,孙雯.老年单纯收缩期高血压患者血脂及血浆同型半胱氨酸水平的变化.天津医科大学学报,2001；7(3)：406-408.
[220]贾灿萍,张旭东,孙恒芳,等.老年单纯收缩期高血压脉压与血同型半胱氨酸及颈动脉内膜-中层厚度相关性研究.中国微循环,2008；12(4)：232-234.
[221]刘坤申,刘刚.血脂异常与高血压.中国实用内科杂志.2004,24(5)：262-265.
[222]Burnett JR, Watts GF. Estimating LDL ApoB:infomania or clinical advance Clin Chem,2008; 54(5):782-784.
[223]Lamarche B,Tchernof A, Moorjani S, et al. Small dense low density lipoprotein particles as a predictor of the risk of ische-mic heart disease in men:prospective results from the Quebee cardrovascular study. Circulation,1997; 95:69-75.
[224]朱俐俐,郭立新,孙明.代谢综合征、脂联素与动脉粥样硬化研究的进展.心血管康复医学杂志,2010；19(1)：102-105.
[225]Liao JK, ShinWS,LeeWY, et al. 10xidized low2density lipop rotein decrea2ses the expression of endothelial nitric oxide syntheses.1J Mol Chem,1995; 270:3192241。
[226]Li D, Yang B, Metha JL10X2LDL induces apop tosis in human coronaryartery endothelial cell:role of PKC, PTK, bcl22 and Fas(J). 1Am J Physicol, 1998,275:H5682761.
[227]Jessup W, Krithardes I, Stocker R. Lipid oxidation in atherogene-sis an overview. Biochem Soc Trans,2004; 32(Ptl):134-138.
[228]郭志刚.甘油三酯代谢在动脉粥样硬化发生中的作用.心血管病学进展,1998；19(5)：295-297.
[229]WHO Expert Committee.1999 World Health Organization International Society of hypertension guidelines for the management of hyperten-sion.J Hypertension,1999; 17(2):151.
[230]国家是食药品监督局.中药新药临床研究指导原则(试行本)(S).北京：国医药科技出版社,2002：73-77.
[231]杨丽丽,余静,常鹏.黄芪对高血压大鼠肾脏血管紧张素转换酶2表达的影响.中华高血压杂志,2007；15(1)：39-43.
[232]郑彩云.黄芪降压作用的实验研究.光明中医,2010；25(4)：613-615.
[233]王正荣,罗红琳,肖静,等.天麻素对动脉血管顺应性以及血流动力学的影响.生物医学工程学杂志,1994；11(3)：197-201.
[234]毛跟年,张嫱,聂萌,等.天麻制剂对家兔血压的影响.陕西科技大学学报,2003；21(4)：50-53.
[235]程黎晖.天麻及其有效成分的药理作用与临床应用.西北药学杂志,2008,23(3)：188-190.
[236]张璐,刘强.茯苓多糖制备工艺及药理作用研究进展.中国实验方剂学杂志,2006；12(4)：61-64.
[237]郁相云,钟建华,张旭.泽泻降血脂药理作用及物质基础研究.中国中医药,2010；8(11)：250.
[238]中医研究院中药研究所.半夏炮制前后药效的比较.中草药,1985；16(4)：21.
[239]李文明,刘洪涛,李秀英.川芎嗪对脂多糖诱导的血管内皮细胞损伤的影响.中国药理学通报,2009；25(11)：1516-21.
[240]LEE W S,YANG H Y, KAO P F, etal.Tetramethylpyrazine downre-gulates angiotensin Ⅱ-induced endothelin-I gene expression in vascular endothe Lial cells. Clinical and experimental Pharmacology and Physiology,2005; 32(10):845-850.
[2]黄琳,王清海,李贵明,等.复方芪麻胶囊对气虚痰浊型高血压患者动态血压的影响.中国实验方剂学杂志,2004；10(5)：57-58.
[3]谭健苗,谭少文.血脂与动脉粥样硬化发展阶段的相关性.中国临床保健杂志.2007；10(4)：337-339.
[4]黄芸,戴闺柱,冯宗忱,等.高甘油三酯血症对血管内皮功能的影响.中华心血管病杂志,2003；31(6)：421-423.
[5]齐科研,黄慧,吕泽平,等.血脂异常与高血压的关联研究.中国老年保健医学.2009；7(1)：43-45.
[6]蒋萍,杨小红.低密度脂蛋白胆固醇、载脂蛋白B与颈动脉粥样硬化斑块的关系.江汉大学学报(医学版),2002；30(1)：28-30.
[7]Moon JY, Kwon HM, Kwon SW, et al. Lipoprotein(a) and LDL particle size are telated to the severity of coronary artery desease. Cardiology,2007; 108(4):282-289.
[8]Beatrix P, Florian T, Elisabeth K, et al. Homocysteine strongly enchances metal-catalyzed LDL oxidation in the p resence of cystine and cysteine [J]. therosclerosis,2003; 168 (1):39-48.
[9]王峥,高枫,郝洪军,等.缺血性脑血管病患者颈动脉斑块与TXB2、OxLDL、Lp(a)、Hcy相关性分析.中国神经精神疾病杂志,2008；34(11)：263-265.
[10]Mili Gupta, Priyanka Sharma, Gitanjali Garg. Plasma homocysteine:an independent or an interactive risk factor for coronary artery disease, Clinical Chimica Acta,2005; 352(1～2):121-125.
[11]秦宁,徐俊伟,苏楠,等.阿托伐他汀治疗血脂正常老年高血压临床观察.心脑血管病防治,2009；9(3)：205-207.
[12]崔淑娴,王立奎,陈杰.调脂治疗对老年收缩期高血压患者脉压的影响[J].中国医师进修杂志,2006；29(11)：63-64.
[13]Ji-Guang Wang, an A. Staessen. The benefit of treating isolated systolic hypertension. Current Hypertension Reperts,2001-7; 3(4).
[14]王立新.老年单纯收缩期高血压研究及治疗进展.中国老年学杂,2007；5(27)：1010-1011.
[15]陈新宇.论肝气虚在老年单纯收缩期高血压病中的表现.中国中医基础医学杂志,1999,5(4)：36.
[16]陆峰,杨传华,王震,等.补肾和络方对老年单纯收缩期高血压的疗效及其安全性评价.河南中医,2007；27(11)：31.
[17]沈丽.补肾益气、温阳利水法治疗老年单纯收缩期高血压病.中国医药学报,2002；17(9)：542.
[18]王劲红.张国伦教授运用益气活血法治疗老年高血压病经验.河北中医,2006；18(4)：247-248
[19]王清海,李桂明,李典鸿.高血压病中医证型分布规律的临床研究.新中医,2005；37(11)：26-27.
[20]MaliziaG, Dino 0, PisaR, et al. Expression of leukocyte adhesion mol eculesin the liver of patients with chronic hepatitis B virus infect ion. Gastroenterology,1991; 100(3):749-755.
[21]楼黎明,徐慧连,杨莉,等.高血压病患者血浆P-选择素、细胞间黏附分子-l的观察.浙江临床医学,2006；8(7)：746—747.
[22]李小兵,冼绍祥,洪永敦,等.高血压患者黏附分子水平异常与痰湿证关系的探讨.江苏中医药,2005；26(6)：15-16.
[23]金国健,樊锦秀,张茂华,等.老年高血压中医证候分型的黏附分子表达与血微循环的关系.浙江临床医学,2006;8(12)：1240-1241.
[24]Vaziri ND, Wang XQ, Oveisi F, et al. Induction of oxidative stress by glutathione depletion cause severe hypertension in normal rats. Hyp ertension,2000; 36(1):142.
[25]黄勇武,杨振汉,李文朗.生脉注射液对老年单纯收缩期高血压患者可溶性黏附分子水平的影响.检验医学与临床,2010；7(6)：1668.
[26]Pickering TG. Stress, inflammation, a nd hypertension. Jcin Hypertens, 2007; 9(7):567-571.
[27]Kim KI,Lee JH, Chang HJ, et al. Association between blood pressure v ariability and inflammatory marker in hypertensive pa-tients. Cite J,2008; 72(2):293-298.
[28]Naya M,Tsukamoto T, Morita K, et al. Plasma interleukin-6 and tumor n ecrosis factor-alpha can predict coronary end othelial dysfunction in h ypertensive patients.Hypertens Res,2007; 30(6):541-548.
[29]Zhang H, Park Y, Wu J, etal. Role of TNF-alpha in vascular dysfuncti on. Clin Sci,2009; 116(3):219-230.
[30]Chen L, Frister A, Wang S, et al. Interaction of vascular smooth musc le cells and monocytes by soluble factors synergis-tically enhances IL-6 and MCP-1 production. Am J Physiol Heart Circ Physiol,2009; 296(4):H987-996.
[31]陈建英,陈晓于,谢晓明,等.生脉注射液对老年单纯收缩期高血压患者TNF-a和IL-6水平的影响.中南药学,2009；7(8)：578-579.
[32]张运,孙肖文,赵云霞.通心络消退动脉粥样硬化斑机制的研究.中国医学论坛报,2004；30(23)：16.
[33]陶军.血管内皮功能心血管疾病治疗靶点.中国医学论坛报,2008；34(35)：C14.
[34]Huraux C, Makita T, Kurz S, et al. Sureroxide productions risk factors and endothelium-dependent relaxations in Human internal marmnary arterie. Circulation,1999; 99(1):53-59.
[35]吴以岭.络病学基础与临床研究,北京：中国科学技术出版社,2005,1：194-197.
[36]刘晶,张燕丽,王雅齐.复方丹参药理药效研究进展.2008,25(6)：23-24.
[37]天士力公司药物研究所.复方丹参滴丸对高脂血症的治疗作用.中国医学论坛报,2002；28(15)：5.
[38]曹铁生,段云有,扬炳昂,等.复方丹参滴丸对高脂血症和动脉粥样硬化的治疗作用-高分子辨率超声成像动态观察研究.中国医学论坛报,2003；29(36)：21.
[39]葛玉霞,段云有,阮骊韬,等.复方丹参滴丸对血管内皮功能的保护作用.中国临床康复,2004；8(6)：1069-1097.
[40]陈频,徐向进,史道华.复方丹参滴丸对胰岛素抵抗大鼠糖脂代谢的影响.中国医学论坛报,2008；34(42)：C8.
[41]温薇.丹参的药理作用及临床应用.中医药信息,2007；24(4)：54-55.
[42]黄美爱,陈晓龙,贾连旺,等.复方丹参滴丸对老年单纯收缩期高血血管内皮依赖性舒张功能的影响.中医药学报,2009；37(2)：32-33.
[43]魏茂提,王世鑫,李玉明,等.单纯收缩期高血压和双相高血压患者血NOS活性及MDA水平的变化.中国慢性病预防与控制,2001；9(4)：149-150.
[44]Tyttell KS,Bostom A, Selhub J, et al.High homocysteine levels&reind ependently related to isolated systolic hyperten-sionin older adults. Cir culation,1997; 96:1745-1749.
[45]曾春雨,刘光耀,王旭,等.老年人收缩期高血压血浆神经肽Y的改变及培哚普利干预的研究.中华老年医学杂志,1998；2(17)：17-18.
[46]Blundell G,Jones BG, Rose FA, et al. Homocysteine mediatd endotheial cell toxicity and its amelior ation. Atherosclerosis,1996; 1221:63.
[47]Lunberg JM, Tatemoto K. Pancreatic polypeptide family(APP, BPP, NPY and PYY)in relation to sympathetic vaso-constriction resistant to a-adre noceptor blockade. Acad Physiol Scand,1982; 116:392-402.
[48]李浩,宋春生,刘方州,等.老年高血压分型与健康老年人血浆同型半胱氨酸、神经肽Y及血脂水平的较研究.中国老年学杂志,2003；8(23)：496-498.
[49]Miller DW, Tessel RE. Age-dependent hyper-responsive pres-sot effects of intravenous neuropeptide Y(NPY):role of mode of peptide admi nistration and plasma NPY. like im. Munoreactivity. Cardiovasc Pharma col,1991; 18:647-651.
[50]李浩,刘芳,崔玲,等.降压胶囊治疗老年单纯收缩期高血压24例临床研究.中医杂志,2004；45(1)：26-28.
[51]李勇,罗心平,范维琥,等.麝香保心丸对动脉壁一氧化氮代谢的影响.中国急救医学,1999；19(8)：451-453.
[52]张奇志,卜培莉,于文强,等.麝香保心丸对自发性高血压大鼠心肌纤维化的干预研究.中西医结合心脑血管病杂志,2008；6(5)：546-548.
[53]Panza JA, Casino PR, Kilmyne CM, et al. Role of endotheli-um-derived ni tric oide ill in the abnomal endotheliurn-de-pendment vasorelaxation of patients with essential hypertension. Circulation,1993; 87:1468-1474.
[54]Kerr S, Brosnan MJ, Melntyre M, et al. superoxide anion production is increased in a model of genetic hypertension:the role of tire end othelium. Hypertens,1999; 33:1353-1358.
[55]谢钢,陈新宇.益气舒肝汤对单纯收缩期高血压病(肝气虚证)患者血浆GSH-PX、CAT的影响.中国现代医药,2005；4(6)：5-6.
[56]贾真,颐复生,通心络胶囊对血管内皮功能的影响.见：吴以岭主编.中医络病学说与心脑血管病-表方药通心络胶囊实验与临床研究.北京：中国科学技术出版社,2001,49：51.
[57]张丽华,刘余芳,何乓一.通心络胶囊治疗高血压80例的疗效.中国新药杂志,1998；7(增刊)：11-12.
[58]卫明,陈可冀.老年高血压病100例疗效观察.交通学报,1994；8(4)：425.
[59]吴晓斌.中医方药对老年高血压病的辨证论治.中国保健营养,2010；5(1)：318.
[60]张剑荣,陈红霞.运用中医经典理论辨证治疗高血压病.新疆中医药,2010；4(28)：93-94.
[61]李秀峰,张瑜珠.高血压病的病因病机、辨证论治及体会.中国医药指南,2009；7(4)：109.
[62]杨臻玉.高血压病辨证论治.新疆中医药,2007；25(4)：6-7.
[63]陈利群,海峰,王维谆.补肾化瘀法治疗老年单纯收缩期高血压60例的临床观.中国老年学杂,2005；10(25)：1236-1237.
[64]顾雄华.降气活血法治疗老年单纯性收缩期高血压36例.中西医结合心脑血管病杂志,2008；6(12)：1398-1399.
[65]虢沛,钱海凌,龚超奇.活血化瘀利水法联合西药治疗老年单纯收缩期高血压病 48例.广西中医药,2009；32(6)：33-34.
[66]李晓.益气化痰方治疗单纯收缩期高血压病47例.中国中医急症,2010；19(1)：124-125.
[67]李思宁,魏丹蕾.苓桂术甘汤治疗老年单纯收缩期高血压的疗效观察.湖北中医杂志,2007；29(7)：27-28.
[68]王子宽.程志清教授诊治中老年高血压病的临床经验[J].浙江中医学院学报,2004,28(1)：21-22.
[69]邹志东,齐放.滋肾温阳法治疗原发性高血压病31例分析.北京中医,2005；24(1)：43—45.
[70]潘力焘,李耀芳,金庆文.健脾平肝降压汤治疗高血压病的临床研究.深圳中西医结合杂志,2007；17(1)：22—24.
[71]田俊,邬渊敏,戴嫣.自拟补肾涤痰化瘀汤治疗高血压病临床观察.中西医结合心脑血管病杂志,2007；5(11)：1044-104.
[72]沈金玲,王守富.化痰平肝饮治疗高血压病60例临床观察.中国中医急症,2008；17(8)：1059—1060.
[73]周红梅.加味半夏白术天麻汤治疗痰湿壅盛型高血压病的临床观察.北京中医药,2008；27(5)：363—365.
[74]何欣,何立人.化湿泄浊方治疗高血压病临床观察.上海中医药杂志,2009；43(11)：36—38.
[75]王耀光.张伯礼教授辨证治疗心脑血管疾病临床用药经验撷拾.中医药通报,2006；5(2)：10—13.
[76]王勉,秦扬.加味血府逐瘀汤治疗高血压64例疗效观察.中国热带医学,2008；8(9)：1564—1595.
[77]孔丽君.补肾降压汤为主治疗老年单纯收缩期高血压32例.浙江中医杂志,2004；4：148-149.
[78]杨晓云.张民.平压止眩汤治疗单纯收缩期高血压48例.福建中医药.2006.37(3)：4-5.
[79]钟志明.滋潜汤治疗单纯收缩期高血压病45例.中国中医药科技,2006；13(2)：131.
[80]杨丁友,刘桂峰,吴兴利.黄芪陷胸胶囊治疗老年单纯收缩期高血压50例临床观察.中国动脉硬化杂志,2007；12(5)：137-140.
[81]王勉,秦扬,李冰.加味大补地黄汤治疗肝肾阴虚型高血压病103例临床分析.中国中药杂志,2008；33(18)：2144—2146.
[82]邹全林.尼群地平联合脑心通治疗老年单纯收缩期高血压临床疗效分析.中国现代药物应用,2009；3(20)：123-124.
[83]李香玉,吴新萍.复方丹参滴丸联合尼莫地平治疗老年单纯收缩期高血压临床疗效分析.中国实用医药,2009；4(3l)：133-134.
[84]郑秀英,陈俊琦.针药联合治疗老年单纯收缩期高血压的临床观察.现代中西医结合杂志,2010；19(19)：2366-2367.
[85]彭丽辉,冯玲媚.艾灸对高血压患者血压及N0、ET、SOD、MDA的影响.中国针灸.2004；24(3)：157—159.
[86]骆传江,徐华龙.中华推拿与西药治疗高血压各50例临床观察.按摩与导引,2002；17(1)：16—17.
[87]武炜,谢飞.生物反馈疗法治疗老年单纯收缩期高血压的临床疗效.中国医药导报,2008；5(29)：31.
[88]龚一萍,倪美文,宋宵红.天麻钩藤饮对高血压肝阳上亢证大鼠一氧化氮、内皮素干预作用的研究.中国中医药信息杂志,2004；11(2)：127-128.
[89]秦彩铃,刘群英,程志铭,等.钩藤、牛膝及二药伍用的实验研究.中国中药杂志,1994；19(6)：271-273.
[90]黄琳红,袁秉祥,贺建宇,等.珍菊降压片对肾性高血压大鼠血压的影响.西安交通大学学报(医学版),2003；24(6)：615-617.
[91]张笑丽,刘子旺.等首乌降压胶囊对肾性高血压大鼠血浆一氧化氮、内皮素水平的影响.光明中医,2005；20(1)：47-48.
[92]张瑛朝,张延敏.复方杜仲叶合剂对人体降压作用的实验研究.中成药,2001；23(6)：418-421.
[93]西北植物所.中草药通讯,1972；(4)：I2.
[94]田川智惠.罗布麻叶提取物的降压作用.KUGAKU ZASSHI,2004；124(11)：851～856.
[95]范维衡.杜仲叶和皮的药理作用研究.药学通报,1979；14(9)：404.
[96]秦振栋.药用植物研究论文选编,西安：西北大学生物系,1983：235.
[97]潘龙,支娟娟.杜仲糖苷对肾性高血压大鼠血压及血浆ET、N0的影响.现代中医药,2010；3(2)：54-56.
[98]吕俊华,杨文豪,熊爱华,等.红丝线草提取物对肾陛高血压模型大鼠降压机制研究.山东中医杂志,2004；23(6)：357-358.
[99]宋纯清,樊懿,黄伟晖,等.钩藤中不同成分降压作用的差异.中草药,2000；31(10)：762-764.
[100]余文海.钩藤对自发性高血压大鼠内皮的影响[J].国外医学·中医中药分册,2000；22(6)：351-352.
[101]怡悦.钩藤对自发性高血压大鼠血管内皮功能的影响.国外医学·中医中药分册,2000；22(1)：28-29.
[102]余俊先,吴芹.异钩藤碱对猫的心血管作用与血药浓度的关系.中国药理学与毒理学杂志,2002；16(3)：191-194.
[103]Shi JS.Wu Q. Liu GX. Effects(If isorhynchophlline on isolated rabbit aortic strip[J]. Acta Acad Med Zunyi(遵义医学院学报),1990；13(4)：16-19.
[104]Zhu Y, Liu GX, Huang XN. Negatively chronotropic and inotropic effects of rhynehophyline and isorhynehophylline on isolated guinea pig atria. Chin Pharmacol Toxicol(中国药理与毒理学杂志),1993；7(2)：117-121.
[105]缪化春,沈业寿.天麻多糖的降血压作用.高血压杂志,2006；7(14)：531.
[106]张梦娟.天麻多糖的提取、纯化和活性研究.北农林科技大学,2007；4(3)：45.
[107]孙中吉,王辉.天麻素注射液的药理作用和临床应用.时珍国医国药,2008；19(4)：1011-1013.
[108]毛跟年,张嫱,聂萌,等.天麻制剂对家兔血压的影响.陕西科技大学学报,2003；21(4)：50-54.
[109]何晓燕,赵淑梅,官汝淳.夏枯草对家兔降压作用机理的研究.通化师范学院学报,2002；23(5)：100.
[110]刘菊秀,苗戊,狄俊英,等.决明子降压作用的实验研究.天津中医,1990；6(5)：37—38.
[111]宋雪鹏,陈平平,柴象柩.葛根素对自发性高血压大鼠的降压作用及其对血浆肾素活性的影响.中国药理学报,1988；9(1)：52.
[112]陈沪生,王培仁,邵建华,等.葛根素的降压效果及其机理的研究.山东医科大学学报,1987；25(3)：28.
[113]黄兆铨,叶武.葛根素对高血压患者血浆内皮素和一氧化氮的影响.中国现代应用药学杂志,1999；16(3)：13.
[114]程能能,马越呜.地龙中降太的类血小板活化因子物质.中国中药杂志,1993；18(12)：747.
[115]李淑兰,谢桂芹,曲竞南,等.地龙降压作用的研究.中医药信息,1995；3：11.
[116]徐天予.全蝎的药理作用及临床新用.中国民族民间医药,2010；29(2)：29-30.
[117]于培明,田智勇,许启泰,等.辛夷研究的新进展.时珍国医国药,2005；16(7)：652-653.
[118]张洪平,李亚娟,章丹丹,等.辛夷二氯甲烷提取物对离体大鼠胸主动脉环的舒张作用及其机制.中国病理生理杂志,2010；26(9)：1689—1694.
[119]陈乐生,寄生药理研究.陕西中医,2000；21(Ⅱ)：520-521.
[120]晏莉.大蒜素药理作用和作用机理的探讨.实用临床医学,2008；9(1)：134-135.
[121]王立新.老年单纯收缩期高血压研究及治疗进展.中国老年学杂志,2007；27(10)：1010-1011.
[122]Ciufetti G, Schillaci G, Lo mbardini R, et al. Plasma viscosity in isolated systolic hypertension:the role of pulse pressure. Am J Hypertens,2005; 18(7):1005-1008.
[123]Kannel WB. Historic perspectives on the relative contributions of diastolic and systolic blood pressure elevation to cardiovascular risk profile. Am Heart J,1999; 138:205-210.
[124]何莉,曾朝荣.单纯收缩期高血压.中华高血压杂志,2007；15(11)：961.
[125]Strandberg TE, Salomaa YY, Vanhanen HT, et al. Isolated diastolic h ypertension, pulse pressure, and mean arterial pressure as predictors o f mortality during a follow-up of up to 32 years. J Hypertens,2002; 20(3):399-404.
[126]Aronson S,Boisvert D, Lapp W. Isolated systolic hypertension is as sociated with adverse outcomes from coronary artery bypass grafting surgery. Anesth Analg,2002; 94(5):1079-1084.
[127]Staessen JA, Gasowski J, Wang JG, et al. Risks of untreated and treat ed isolated systolic hypertension in the elderly:meta-analysis of outcome trials. Lancet,2000; 355(9207):865-872.
[128]陆再英,钟南山.内科学,北京：人民卫生出版社,2009,第7版：251-252.
[129]陈维清,吴系科.老年单纯收缩期高血压的病因探讨：病例对照研究.安徽医科大学学报,1992；27(2)：91-94.
[130]赵树柚摘译.国外医学老年医学分册,1989；9(2)：83.
[131]Dyer AR et al.J Chroa Dis.1982; 35:259.
[132]Dyer AR et al.J Chron Dis.1982; 35:275.
[133]Mecclellan W et al.Prev Med,1987; 16:686.
[134]Kannel WB et al. In Buljitt CJ ed. Epidemiology of Arterial Blood Pressur.Hugue:Martinus Ni jhoff,1980:256.
[135]Colandrea MA et al. Circulation,1970,41:239.
[136]张明华.单纯收缩期高血压的特点及治疗研究进展.中华临床医药,2004：5(10)：57-60.
[137]Fagard R H. Epidemiology of hypeertension in the elderly.Am J Geriatr Cardiol,2002; 11(1):23-28.
[138]Bog-Hansen E. Impaired glucose metabolism and obesity in Swedish patients with borderline isolated systolic hypertension:Skaraborg Hypertension and Diabetes Project. Diabetes Obes Metab,2001; 3(1):25-31.
[139]Martins D, Nelson K, Pan D, et al. The effect of gender on age-related blood pressure changes and the prevalence of isolated systolic hypertension among older adults:data from NHANES Ⅲ. J Gend Specif Med,2001; 4(3): 10-20.
[140]Banega JR, de-la-Cruz JJ, Rodriguez-ArtalejoF,et al. Systolic vs diastolic blood pressure:community burden and impact on blood pressure staging. J Hum Hypertens,2002; 16(3):163-167.
[141]Yeh CJ, Pan WH, Jong YS, et al. Incidence and predictors of isolated systolic hypertension and isolated diastolic hypertension in Taiwan. J Formos Med Assoc,2001; 100(10):668-675.
[142]Manfredini R, Boari B, Portaluppi F. Morning surge in blood pressure as a predictor of silent and clinical cerebrovascuLar disease in elderly hypertensives.Circulation,2003; 108(10):e72-e73.
[143]Glynn RJ, Chae CU, Guralnik JM, et al. Pulse pressure and mortality in order people.Arch intern Med,2000; 160:2765-72.
[144]黄玫,李晓天,王丹丹.老年单纯收缩期高血压的危险因素与药物治疗.中国老年学杂志,2008：28(24)：2503-2505.
[145]Kannel WB. Historic perspectives on the relative contributions of diastolic and systolic blood pressure elevation to cardiovascular risk profile.Am Heart J,1999; 138:205-210.
[146]Safar ME. Systolic blood pressure,pulse pressure and arterial stifness as cardiovascular risk facters. Curt Opin Nephrol Hypertens,2001; 10(2):257-61.
[147]KawasakiT,SasayamaS, YagiS, et al.Non invasive assessment of the age related changes in stiffness of major branches of the human arteries. CardiovascRes,1987; 21 (9):.678-87.
[148]AvolioAP, ChertSG, WangRP, etal. Effectsof agingon changing arterial compliance and left ventricular load in a northern Chinese urban community.Circulation,1983; 68(1):50-58.
[149]Rourke MF. Arterial stiffness, systolic blood pressure and lngi caltreatment of arterial hypertension. Hypertension,1990; 15:45.
[150]马淑平,王国华,计承.老年单纯收缩期高血压问题的再探讨.河北医药,2004；26(10)：817.
[151]Vasari RS, Beiser A, Seshadri S, et al. Residual liffetime risk for de-veloping hypertension in middle-aged woman and man. JAMA,2002; 287(8):1003-1010.
[152]谭静,华琦,闻静,等.老年单纯收缩期高血压患者动脉僵硬度的临床研究.中华老年多器官疾病杂志,2007；6(6)：396-398.
[153]陈雯,郭进,王风,等.老年冠心病合并高血压患者血管内皮功能的改变.中国老年学杂志,2005；25(11)：1353—5.
[154]何莉,曾朝荣.单纯收缩期高血压.中华高血压杂志,2007；15(11)：961-962.
[155]李芳,姚丽霞,苑晓烨,等.老年高血压患者凌晨血压增高与血管内皮功能的相关性研究.山东医药,2010；50(33)：53-54.
[156]叶琳.内皮功能障碍及治疗对策.心血管病学进展,2000；21：245-248.
[157]李浩,蔡琳琳.老年单纯收缩期高血压诊治的若干问题探讨.世界中西医结合杂志,2009；4(11)：828-831.
[158]潘宏伟,周胜华,等.单纯收缩期高血压患者的心率震荡与心率变异.临床心血管病杂志[J].2007,23(10)：728-730.
[159]邓烈华,黄榕,邬真力,等.单纯收缩期高血压患者脉搏波传导速度与心率变异性.中华高血压杂志,2008；16(11)：987-990.
[160]陆再英,钟南山.内科学,北京：人民卫生出版社,2009,第7版：253.
[161]Dendorfer A, Dominiak P, Schunkert H. ACE inhibi-tors and angiotensin Ⅱ receptor antagonists. Handb Exp Pharmacol,2005; 170:407-442.
[162]Irita J, Okura T, Manabe S, et al. Plasma osteopontin levels are higher in patients with primary aldosteronism than in patients with essential hypertension.Am J Hy-pertens,2006; 19(3):293-299.
[163]孙海燕.肾素-血管紧张素系统在高血压发病机制及药物治疗中的作用.深圳职业技术学院学报,2005；2(4)：43-47.
[164]孙晓方,肖新华.ARB降压机制及降压外的作用.药品评价,2009；6(4)：129-131.
[165]中华医学会糖尿病学分会代谢综合征研究协作组.中华医学会糖尿病学分会关于代谢综合征的建议.中华糖尿病杂志,2004；12(3)：156—161.
[166]Sarzani R, Salvi F,Dessl-Fulgheri P, et al. Renin-angiotensin sys-tem, Natriuretic peptides, obesity, metabolic syndrome, and hyper-tension:an Integrated view in humans. J Hypertens,2008; 26(5):831-843.
[167]Defronzo RA, Kashyap SR. The insulin resistance syndrome:physi-ological considerations.J Hypertens,2008; 26(5):831-843.
[168]翁春艳,江凤林,袁洪.胰岛素抵抗性高血压病的发病机制与治疗.医学综述,2009；15(4)：569-571.
[169]Potenza MA, Marasciulo FL, Chieppa DM, et al. insulin resistance in spontaneously hypertensive rats in associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production.AM J Physiol Heart Circ Physiol,2005; 289(2):813-822.
[170]Schillaci G, Pirro M, Gemelli F, et al.Increased C-reactive protein concentrations in never-treated hypertension:the role of systolic and pulse pressures. Hypertens,2003; 21:1841-1846.
[171]Sesso HD, Buring J E, Rifai N, Blake GJ, et al. C-reactive protein and the risk of developing hypertension.JAMA,2003; 290:2945-2951.
[172]Hayaishi-Okano R, Yamaaki Y, Katakami N, et al. Elevated C-reactive protein associates with early-stage carotid atheosclero-sis in young subjects with type diabetes.Diabetes Care,2002; 25:1432-1438.
[173]Fichtlscherer S, Rosenberer G, Disk H, et al. Elevated C-reactive protein levels and impaired endothelial vasoreactivity in pa-tients with coronary artery disease. Circulation,2002; 102:1000-1006.
[174]陈丽,高兴玉,张俊,等.老年高血压肱动脉内皮功能、颈动脉粥样硬化与血清肿瘤坏死因子α、白介素6关系的研究.四川医学,2005；26(5)：511-513.
[175]黎镇垣,马中富,甄慰毅,等.动态观察高血压患者血清白细胞介素18改变的临床意义.标记免疫分析与临床,2003；10：1-3.
[176]罗文利,李南方,柳达.老年单纯收缩期高血压与部分炎症因子的相关性分析.Chinese General Practice,2010; 13(9):3079-3080.
[177]刘建交,季光,等.药理实验方法学[J].2003.190—195.
[178]Martin Liebetrau, Dorothe Burggraf, Nathalie Wunderlich,et al. Hamann ACE inhibitation reduces activity of the plaminogen plasmin and MMP systems in the brain of spontaneous hypertensive stroke-prone rats. Neuroscience Letters,2005; 376:205-209.
[179]Alan R. Olzinskia, Tara A. McCaffertyb. Shufang Q, Zhaoc,etal. Hypertensive target organ damage is attenuated by a p38 MAPK inhibitor; Role of systemic blood pressure and endotheilal protection. Cardiovascular Research,2005; 66:170-178.
[180]周颖,陈虹,王明远,等.高血压动物模型研究进展.中国现代实用医学杂,2006；5(1)：51.
[181]Abdi A, Johns EJ. Importance of the rennin angiotensin system in he genetation of kedney failure in renovascular hypertension. J Hypertens, 1996; 14:1131-1137.
[182]Ramirez M, Pricto I, Martinez JM, et al. Renal a inopepti dase activities in animal models of hypertension. Cardiovascular Research,2007; 45: 176-178.
[183]Mercedes Losadaa, Sonia H, Torresb, et al.Amparo Sos Muscle arteriolar and venular reactivity in two models of hypertensive rats. Microvascular Research,2005; 69:142-148.
[184]Leenen FH, de Jong W. A solid silver clip for induction of predictavle levels of renal hypertension in the rate. J Appl physiol,1971; 31: 142-144.
[185]Fuji J, Kurihar H, Yamaguchi H, et al. A persistent hyperten-sion due to unilateral renal artery constriction in the rabbit. Jpn Circ J,196731: 1197-2000.
[186]Anderson WP, Ramsey DE,Takata M. development of hyper-tension from unilateral renal artery stenosis in conscious dogs. Hypertension, 1990; 16:441-451.
[187]Panek RL, Ryan MJ, Weishaar RE, et al. Development of a high renin model of hypertension in the cynomolgus monkey.Clin Exp Hypertens A,1991; 13:1395-1414.
[188]Leene FH, de Jong W. Plasma renin and sodium balance during development of moderate and sever renal hypertension in rats. Circ Res,1975; 36: S179-186.
[189]王立文,刘光耀.左侧植入路二肾一夹法复制肾血管性高血压大鼠动物模型.第三军医大学学报,1998；20(5)：394-395.
[190]杨宁,胡立斌,张中,等.肾血管性高血压动物模型建立及指标监测.中华放射学杂志,2002；11(2)：117-119.
[191]曹珊珊,李瑞芳,等.肾性高血压大鼠模型制作的改良方法.河南科技大学学报(医学版).2010,28(3)：165-167.
[192]杨志华,盛文利,侯清华,等.双肾双夹肾血管性高血压模型的制作与术后管理.中国比较医学杂志,2005；15(2)：54-56.
[193]Hall JE, Kuo JJ, da Silva AA, et al. Obesity-associated hyper-tension and kidney disease. Curr Opin Nephrol Hypertens,2003; 12:195-200.
[194]周颖,陈虹,王明远,等.高血压动物模型研究进展.中国现代实用医学杂,2006；5 (1)：52.
[195]沈加林,陈克敏,许建荣,等.球囊固定动脉法延髓神经血管压迫建立高血压动物模型的实验研.中华放射学杂志,2002；36(9)：773—775.
[196]张晓华,李善泉,沈加林,等.原发性高血压犬模型的建立[J].上海第二医科大学学报,2003；23(5)：406-408.
[197]张艳荣,张连峰,杨志伟.高血压实验动物模型.中华高血压杂志,2008；16(3)：205-207.
[198]王秀卿,高贞,郭红,等.慢性应激性高血压动物模型的建立.白求恩军医学院学报,2003；1(4)：202—203.
[199]Mullins JJ, Peters J, Ganten D. Fulminant hypertension in trans-genic rats harbouring the mouse Ren-2 gene. Nature,1990; 334:541-544.
[200]Kim HS, Krege JH, Kluckman KD, et al. Genetic control of blood pressure and the angiotensinogen locus. Proc Natl Acad Sci USA,1995; 92:2735-2739.
[201]Sugiyama F, Haraoka S, Watanabe T, et al. Acceleration of ath-erosclerotic lesions in transgenic mice with hypertension by the activated renin-angiotensin system. Lab Invest,1997; 76: 835-842.
[202]Pitzalis MV, Sarzani R, Dessi-Fulgheri P, et al.Allelic variants of natriuretic peptide receptor genes are associated with familily history of hypertension and cardiovascular phenotype. J Hy-pertens ,2003; 21:1491-1496.
[203]Oliver PM,Fox JE, Kim R, et al. Hypertension, cardiac hyper-trophy, and sudden death in mice lacking natriuretic peptide re-cepter A.Proc Natl Acad Sci USA,1997; 94:14730-14735.
[204]Sugiyama F, Yagami K, Paigen B. Mouse models of blood press-ure regulation and hypertension. Curr Hypertens Rep,2001; 3:41-48.
[205]Yang Z, Sibley DR, Jose PA. D5 dopamine receptor knock out mice and hypertension.J Recept Signal Transduct Res,2004; 24:149-164.
[206]Kurihara Y, Kurihara H, Suzuki H, et al. Elevated blood pres-sure and craniofacial abnormalities in mice deficient in endothelin-1. Nature,1994; 368:703-710.
[207]Atkinson J, Poitevin P, Chinllon JM, et al. Vascular calcium over loadp reduced by vitaminD3 plus nicotine treatment diminishes arterial distensibility in rats. Am J Physionl,1994; 266:H540-H547.
[208]Essalihi R, Dao HH, Yamaguchi N, et al.A new model of i-solated systolic hypertension induced by chronic warfarin and vitamin Kl treatment. Am J Hypertens,2003; 16(2):103-110.
[209]Donnell CJ, Shea MK, Price PA, et al. Matrix gla protein is associated with risk factors for atherosclerosis but not with coronary artery calcification. Arterioscler Thromb Vasc Bi-ol,2006; 26(12):2769-2774.
[210]刘承云,万晶晶,杨群芳,等.阿托伐他汀对华法林致大鼠主动脉中膜钙化及收缩压升高的影响.中国医院药学杂志,2008；28(21)：1733-1736.
[211]陈宁,吕圭源,陈素红.抗高血压新药及血灵降压机制研究进展.中国现代药物应用,2010；4(2)：85-87.
[212]YUNKER A M. Modulation and pharmacology of low voltag e-ac-tivated (T-Type) calcium channels. J Bioenerg Biomembr,2003; 35(6):557-598.
[213]曾春雨,刘光耀.脑内神经肽Y受体亚型与抗高血压药物的研究进展.国外医学药学分册,1997；24(2)：88-92.
[214]王俊敏.抗高血压药物的研究进展.医药论坛杂志,2005；26(1)：77-78.
[215]李兴凯,陈雅琴.复方抗高血压药物的研究应用及发展前景.实用药物与临床,2005；(8)：43-44.
[216]Essalihi IL Dao HH, Yamaguchi N, et al.A new model of isolated systolic hypertension induced by chronic warfarin and vitamin k1 treatment. Am J Hypertens,2003; 16:103-110.
[217]薛洁,谢梅林.中药血清药理学的方法研究近况.中草药,2003；34(6)：附9-11.
[218]李仪奎.中药血清药理学实验方法的若干问题.中药新药与临床药理,1999；10(2)：95-98.
[219]冯淑芝,张佚,孙雯.老年单纯收缩期高血压患者血脂及血浆同型半胱氨酸水平的变化.天津医科大学学报,2001；7(3)：406-408.
[220]贾灿萍,张旭东,孙恒芳,等.老年单纯收缩期高血压脉压与血同型半胱氨酸及颈动脉内膜-中层厚度相关性研究.中国微循环,2008；12(4)：232-234.
[221]刘坤申,刘刚.血脂异常与高血压.中国实用内科杂志.2004,24(5)：262-265.
[222]Burnett JR, Watts GF. Estimating LDL ApoB:infomania or clinical advance Clin Chem,2008; 54(5):782-784.
[223]Lamarche B,Tchernof A, Moorjani S, et al. Small dense low density lipoprotein particles as a predictor of the risk of ische-mic heart disease in men:prospective results from the Quebee cardrovascular study. Circulation,1997; 95:69-75.
[224]朱俐俐,郭立新,孙明.代谢综合征、脂联素与动脉粥样硬化研究的进展.心血管康复医学杂志,2010；19(1)：102-105.
[225]Liao JK, ShinWS,LeeWY, et al. 10xidized low2density lipop rotein decrea2ses the expression of endothelial nitric oxide syntheses.1J Mol Chem,1995; 270:3192241。
[226]Li D, Yang B, Metha JL10X2LDL induces apop tosis in human coronaryartery endothelial cell:role of PKC, PTK, bcl22 and Fas(J). 1Am J Physicol, 1998,275:H5682761.
[227]Jessup W, Krithardes I, Stocker R. Lipid oxidation in atherogene-sis an overview. Biochem Soc Trans,2004; 32(Ptl):134-138.
[228]郭志刚.甘油三酯代谢在动脉粥样硬化发生中的作用.心血管病学进展,1998；19(5)：295-297.
[229]WHO Expert Committee.1999 World Health Organization International Society of hypertension guidelines for the management of hyperten-sion.J Hypertension,1999; 17(2):151.
[230]国家是食药品监督局.中药新药临床研究指导原则(试行本)(S).北京：国医药科技出版社,2002：73-77.
[231]杨丽丽,余静,常鹏.黄芪对高血压大鼠肾脏血管紧张素转换酶2表达的影响.中华高血压杂志,2007；15(1)：39-43.
[232]郑彩云.黄芪降压作用的实验研究.光明中医,2010；25(4)：613-615.
[233]王正荣,罗红琳,肖静,等.天麻素对动脉血管顺应性以及血流动力学的影响.生物医学工程学杂志,1994；11(3)：197-201.
[234]毛跟年,张嫱,聂萌,等.天麻制剂对家兔血压的影响.陕西科技大学学报,2003；21(4)：50-53.
[235]程黎晖.天麻及其有效成分的药理作用与临床应用.西北药学杂志,2008,23(3)：188-190.
[236]张璐,刘强.茯苓多糖制备工艺及药理作用研究进展.中国实验方剂学杂志,2006；12(4)：61-64.
[237]郁相云,钟建华,张旭.泽泻降血脂药理作用及物质基础研究.中国中医药,2010；8(11)：250.
[238]中医研究院中药研究所.半夏炮制前后药效的比较.中草药,1985；16(4)：21.
[239]李文明,刘洪涛,李秀英.川芎嗪对脂多糖诱导的血管内皮细胞损伤的影响.中国药理学通报,2009；25(11)：1516-21.
[240]LEE W S,YANG H Y, KAO P F, etal.Tetramethylpyrazine downre-gulates angiotensin Ⅱ-induced endothelin-I gene expression in vascular endothe Lial cells. Clinical and experimental Pharmacology and Physiology,2005; 32(10):845-850.