益气养阴化瘀通脉法对糖尿病大鼠大血管细胞间粘附分子1（ICAM-1）表达的影响
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摘要
目的:益气养阴化瘀通脉方(由黄芪、白芍、山萸肉、茯苓、白术、葛根、生地、玄参、麦冬、当归、川芎、丹参、桃仁、红花、木香组成)具有益气养阴、活血化瘀、通脉止痛的作用。导师张庚良教授经多年临床实践发现,在糖尿病早期应用益气养阴化瘀通脉法能够起到防治糖尿病大血管病变的效果。本实验通过建立糖尿病大鼠模型,施予药物干预,观察益气养阴化瘀通脉法对糖尿病大鼠大血管内皮组织形态学和细胞间粘附分子1(ICAM-1)表达的影响,讨论本方保护大血管内皮的作用机制。
方法:清洁级雄性Wistar大鼠46只,200~220g,自由饮水进食,饲养于18℃～22℃明暗各12小时的清洁级动物实验室内。正常喂养1周后,随机分出10只作为正常对照组,其余大鼠用于造模,参照相关文献,给予1%的链脲佐菌素枸橼酸缓冲液(枸橼酸缓冲液为0.1mmol/L,pH4.5)55mg/kg体重单次腹腔注射,正常组给予相应的1%柠檬酸-柠檬酸钠溶液注射。72h后尾静脉采血,测定血糖浓度≥16.7mmol/L,大鼠尿量及饮水量明显增多,则造模成功。
将成模的大鼠随机分为模型对照组、益气养阴化瘀通脉组(简称中药组),辛伐他汀组(简称西药组),每组12只。分组后各治疗组按成人剂量的10倍开始灌胃,每日一次。中药组给予益气养阴化瘀通脉方每日10ml/kg体重(相当于3.6g/ml生药),西药组给予辛伐他汀溶液每日5ml/kg体重(相当于0.4mg/ml原药),正常对照组与模型对照组每日给予相应中药体积的生理盐水灌胃。共灌胃12周。于末次灌胃后禁食不禁水12h,2%戊巴比妥钠腹腔注射麻醉后取材制作标本,用于光镜下观察大血管内皮组织形态学变化,免疫组化法测定大血管细胞间粘附分子1的表达情况。
结果:
1一般行为观察
实验期间,正常组的大鼠精神状态良好,饮食、饮水正常,体重增长明显,皮毛光滑,行动敏捷。模型组的大鼠则表现精神萎靡,多饮、多食、多尿,并逐渐出现形体消瘦,毛色枯黄、蓬松,反应迟钝等情况。有些大鼠出现半身不遂,头部震颤,白内障等症状。中药组和西药组大鼠表现均较模型组为轻。模型组和西药组各死亡2只,1只死于灌胃,2只死于互相撕咬、感染,另1只考虑死于偏瘫不能进食。
2各组大鼠血糖以及体重的变化
与正常组比较,模型组及两个治疗组血糖明显升高,差别有统计学意义(P<0.01);而西药组与模型组之间比较血糖变化不明显,无统计学意义(P>0.05);中药组与模型组比较血糖明显下降,差别有统计学意义(P<0.01)。
与正常组比较,模型组及两个治疗组体重明显下降,有统计学意义(P<0.01);模型组与两个治疗组之间比较,体重明显下降(P<0.01)。两治疗组之间相比较,中药组体重有所增加,但是差别无统计学意义(P>0.05)。
3各组大鼠血脂的变化
模型组、中药组及西药组的甘油三酯(TG)和胆固醇(TC)都明显高于正常组(P<0.05);与模型组相比,两个治疗组明显降低,差别有统计学意义(P<0.05);两个治疗组之间比较,西药组的血脂比中药组降低,但差别无统计学意义(P>0.05)。
4对实验性糖尿病大鼠大血管内皮组织形态学的影响
正常组细胞的纹理清晰,走形正常,胞浆的着色均匀,动脉的内皮细胞扁平,内膜平坦,中膜的平滑肌细胞(smooth muscle cell, SMC)与弹力板近似平行相间排列。模型组的大鼠胸主动脉壁出现局限性的内膜增厚,中膜浅层的平滑肌细胞(SMC)可见增生、紊乱,病灶处的弹力板呈不规则波浪状排列,偶见断裂分离现象。中药组及西药组的组织形态变化均比模型组有明显减轻。
5对实验性糖尿病大鼠大血管细胞间粘附分子1(ICAM-1)表达的影响与正常组比较,模型组及两个治疗组的大鼠胸主动脉内皮细胞中细胞间粘附分子1(ICAM-1)的表达明显高于正常组(P<0.01)。经药物干预后,两个治疗组与模型组比较,ICAM-1表达均明显减少(P<0.05),差别有统计学意义。其中,中药组与西药组比较差别无统计学意义(P>0.05)。
结论:
1益气养阴化瘀通脉方可以明显改善糖尿病大鼠大血管内皮组织的病变程度,说明本方对大血管内皮具有保护作用。
2益气养阴化瘀通脉方对大血管病变的防治作用可能与其降低血糖,改善脂代谢,抑制细胞间粘附分子1(ICAM-1)的表达有关。
Objective: Yiqiyangyinhuayutongmaifang (It is composed of huangqi, gegen, shengdi, maidong, xuanshen, danshen, chuangxiong, danggui, taoren, honghua, muxiang) has efficacy of yiqiyangyin, huoxuehuayu, tongmaizhitong. After years of clinical practice, Mentor Professor Zhang Gengliang found that yiqiyangyinhuayutongmai therapy can play a prevention and treatment effect on diabetic vascular disease in early stage of diabetes. In this study, through the establishment of diabetic rats model, and exerting medicine intervention, to observe the effect of yiqiyangyinhuayutongmai therapy on large vascular endothelail tissue and the expression of intercellular adhesion molecule 1 (ICAM-1) in diabetic rats .
Methods: 46 clean grade male of Wistar rats, weight from 200g to 220g, drink water and take food freely, and were raised in sanitary experiment lab that temperature was 18℃~22℃, bright and dim alternate every 12 hours. After one week, select randomly 10 rats as the normal control group, the remaining rats were used for modeling. According to reference documents, the remaining rats were injected with streptozotocin (STZ) in abdominal cavity, which was dissolved into 1% buffer solution of citric acid of STZ according to 55mg/kg, the normal group were injected with the corresponding 1% citric acid - sodium citrate. After 72 hours later, to test blood glucose. We select the rats which urine and water intake increased significantly and the numerical value of the blood glucose more than 16.7mmol/L.
The diabetic rats were randomly divided into model control group, yiqiyangyinhuayutongmai group (called traditional Chinese medicine group for short), simvastatin group (called Western medicine group for short), and 12 rats in each group. Then, the drugs started be given to the rats according to adult dosage 10 times, daily one time. The rats of Chinese medicine group were given the yiqiyangyinhuayutongmaifang 10ml/kg weight per day(equivalent to 3.6g/ml herbs)by gavage, the Western medicine group were given the simvastatin 5ml/kg weight per day(equivalent to 0.4mg/ml simvastatin)by gavage, the normal group and model group were given the corresponding quantity’s physiological saline by gavage. Each group was given the medicine for 12 weeks. At the end of the experiment, the rats were forbidden to eat for 12h. All rats were anesthetized by injecting 2% napental into abdomen, at the same time, to get the specimen, and observe the change of pathomorphism of large vascular endothelail under light microscope. The immunohistochemical method was used to detect the expression of intercellular adhesion molecule 1 (ICAM-1) in large vascular endothelail.
Results:
1 General observation of behavior of all the rats
During the experiment, the normal rats grow well, have normal diet normal, and weight gain significantly. But the modle group showed apathetic, more drink, more food, polyuria, weight loss obviously and shape gradually thinner, color dry-taek and fluffy, the reaction retardation. Some even appeared hemiplegica, head tremor, cataracta and other symptoms. Two treatment groups showed a similar performance, but the performance of treatment groups alleviated than of the model group. There were two deaths in each group of model group and Western medicine group. Cause of the death was gavage, bites from each other, infection, and starvation.
2 The blood glucose and body weight of the rats in each group
Compared with the normal group, the blood glucose of the model group and two treatment groups was significantly higher (P<0.01), but the blood glucose of model group and Western medicine group was not of significant differences (P>0.05), the blood glucose of the traditional Chinese medicine group was significantly lower than model group (P<0.01).
Compared with the normal group, the body weight of the model group and two treatment groups decreased significantly (P<0.01). But the body weight of treatment groups was significantly higher (P<0.01) than the model group. The two treatment groups was not of significant differences (P>0.05).
3 The cholesterol (TC) and triglyceride (TG) changes of each group
The TC and TG of model group, traditional Chinese medicine group and Western medicine group were significantly higher than of normal group(P<0.05). Two treatment groups compared with the model group decreased significantly(P<0.05), but comparison between the two treatment groups had no significant difference(P>0.05).
4 Effect of Yiqiyangyinhuoyutongmaifang on experimental diabetic rats’large vascular endothelial morphology
The results showed that normal cell texture clear and take the normal shape, color uniform cytoplasm, flat artery endothelial cells, endometrial flat, smooth muscle cells(SMC) and elastic parallel plate order. Model rats’artery wall thickening of the endometrium appeared limitations, the smooth muscle cells in the film shallow proliferation mild, arranged in disorder, with lesions department interwoven arrangement, separation fracture. Rats’artery vascular endothelial morphology of the two control groups changed more lightly than the model group.
5 Effect of Yiqiyangyinhuoyutongmaifang on the expression of the intercellular adhesion molecule 1 (ICAM-1) in the diabetic rats’large vascular
Compared with normal group, the expression of the intercellular adhesion molecule 1 (ICAM-1) in the model rats’thoracic aortic endothelial cells was significantly higher than the normal group (P <0.01). After drug treatment, the treatment group compared with the model group, the expression of ICAM-1 was significantly reduced (P<0.05), the difference was statistically significant. The traditional Chinese medicine group compared with the western medicine group had no significant difference (P>0.05).
Conclusions:
1 Yiqiyangyinhuayutongluofang could be marked improve the histological lesions of diabetic rats’large vascular endothelial. It showed that Yiqiyangyinhuayutongluofang have a protective effect of the large vascular endothelial.
2 Yiqiyangyinhuayutongluofang can protect and cure diabetic macroangiopat- hy, which may be related to that it can improve lipid metabolism, reduce the blood glucose and the expression levels of intercellular adhesion molecule 1 (ICAM-1).
方法:清洁级雄性Wistar大鼠46只,200~220g,自由饮水进食,饲养于18℃～22℃明暗各12小时的清洁级动物实验室内。正常喂养1周后,随机分出10只作为正常对照组,其余大鼠用于造模,参照相关文献,给予1%的链脲佐菌素枸橼酸缓冲液(枸橼酸缓冲液为0.1mmol/L,pH4.5)55mg/kg体重单次腹腔注射,正常组给予相应的1%柠檬酸-柠檬酸钠溶液注射。72h后尾静脉采血,测定血糖浓度≥16.7mmol/L,大鼠尿量及饮水量明显增多,则造模成功。
将成模的大鼠随机分为模型对照组、益气养阴化瘀通脉组(简称中药组),辛伐他汀组(简称西药组),每组12只。分组后各治疗组按成人剂量的10倍开始灌胃,每日一次。中药组给予益气养阴化瘀通脉方每日10ml/kg体重(相当于3.6g/ml生药),西药组给予辛伐他汀溶液每日5ml/kg体重(相当于0.4mg/ml原药),正常对照组与模型对照组每日给予相应中药体积的生理盐水灌胃。共灌胃12周。于末次灌胃后禁食不禁水12h,2%戊巴比妥钠腹腔注射麻醉后取材制作标本,用于光镜下观察大血管内皮组织形态学变化,免疫组化法测定大血管细胞间粘附分子1的表达情况。
结果:
1一般行为观察
实验期间,正常组的大鼠精神状态良好,饮食、饮水正常,体重增长明显,皮毛光滑,行动敏捷。模型组的大鼠则表现精神萎靡,多饮、多食、多尿,并逐渐出现形体消瘦,毛色枯黄、蓬松,反应迟钝等情况。有些大鼠出现半身不遂,头部震颤,白内障等症状。中药组和西药组大鼠表现均较模型组为轻。模型组和西药组各死亡2只,1只死于灌胃,2只死于互相撕咬、感染,另1只考虑死于偏瘫不能进食。
2各组大鼠血糖以及体重的变化
与正常组比较,模型组及两个治疗组血糖明显升高,差别有统计学意义(P<0.01);而西药组与模型组之间比较血糖变化不明显,无统计学意义(P>0.05);中药组与模型组比较血糖明显下降,差别有统计学意义(P<0.01)。
与正常组比较,模型组及两个治疗组体重明显下降,有统计学意义(P<0.01);模型组与两个治疗组之间比较,体重明显下降(P<0.01)。两治疗组之间相比较,中药组体重有所增加,但是差别无统计学意义(P>0.05)。
3各组大鼠血脂的变化
模型组、中药组及西药组的甘油三酯(TG)和胆固醇(TC)都明显高于正常组(P<0.05);与模型组相比,两个治疗组明显降低,差别有统计学意义(P<0.05);两个治疗组之间比较,西药组的血脂比中药组降低,但差别无统计学意义(P>0.05)。
4对实验性糖尿病大鼠大血管内皮组织形态学的影响
正常组细胞的纹理清晰,走形正常,胞浆的着色均匀,动脉的内皮细胞扁平,内膜平坦,中膜的平滑肌细胞(smooth muscle cell, SMC)与弹力板近似平行相间排列。模型组的大鼠胸主动脉壁出现局限性的内膜增厚,中膜浅层的平滑肌细胞(SMC)可见增生、紊乱,病灶处的弹力板呈不规则波浪状排列,偶见断裂分离现象。中药组及西药组的组织形态变化均比模型组有明显减轻。
5对实验性糖尿病大鼠大血管细胞间粘附分子1(ICAM-1)表达的影响与正常组比较,模型组及两个治疗组的大鼠胸主动脉内皮细胞中细胞间粘附分子1(ICAM-1)的表达明显高于正常组(P<0.01)。经药物干预后,两个治疗组与模型组比较,ICAM-1表达均明显减少(P<0.05),差别有统计学意义。其中,中药组与西药组比较差别无统计学意义(P>0.05)。
结论:
1益气养阴化瘀通脉方可以明显改善糖尿病大鼠大血管内皮组织的病变程度,说明本方对大血管内皮具有保护作用。
2益气养阴化瘀通脉方对大血管病变的防治作用可能与其降低血糖,改善脂代谢,抑制细胞间粘附分子1(ICAM-1)的表达有关。
Objective: Yiqiyangyinhuayutongmaifang (It is composed of huangqi, gegen, shengdi, maidong, xuanshen, danshen, chuangxiong, danggui, taoren, honghua, muxiang) has efficacy of yiqiyangyin, huoxuehuayu, tongmaizhitong. After years of clinical practice, Mentor Professor Zhang Gengliang found that yiqiyangyinhuayutongmai therapy can play a prevention and treatment effect on diabetic vascular disease in early stage of diabetes. In this study, through the establishment of diabetic rats model, and exerting medicine intervention, to observe the effect of yiqiyangyinhuayutongmai therapy on large vascular endothelail tissue and the expression of intercellular adhesion molecule 1 (ICAM-1) in diabetic rats .
Methods: 46 clean grade male of Wistar rats, weight from 200g to 220g, drink water and take food freely, and were raised in sanitary experiment lab that temperature was 18℃~22℃, bright and dim alternate every 12 hours. After one week, select randomly 10 rats as the normal control group, the remaining rats were used for modeling. According to reference documents, the remaining rats were injected with streptozotocin (STZ) in abdominal cavity, which was dissolved into 1% buffer solution of citric acid of STZ according to 55mg/kg, the normal group were injected with the corresponding 1% citric acid - sodium citrate. After 72 hours later, to test blood glucose. We select the rats which urine and water intake increased significantly and the numerical value of the blood glucose more than 16.7mmol/L.
The diabetic rats were randomly divided into model control group, yiqiyangyinhuayutongmai group (called traditional Chinese medicine group for short), simvastatin group (called Western medicine group for short), and 12 rats in each group. Then, the drugs started be given to the rats according to adult dosage 10 times, daily one time. The rats of Chinese medicine group were given the yiqiyangyinhuayutongmaifang 10ml/kg weight per day(equivalent to 3.6g/ml herbs)by gavage, the Western medicine group were given the simvastatin 5ml/kg weight per day(equivalent to 0.4mg/ml simvastatin)by gavage, the normal group and model group were given the corresponding quantity’s physiological saline by gavage. Each group was given the medicine for 12 weeks. At the end of the experiment, the rats were forbidden to eat for 12h. All rats were anesthetized by injecting 2% napental into abdomen, at the same time, to get the specimen, and observe the change of pathomorphism of large vascular endothelail under light microscope. The immunohistochemical method was used to detect the expression of intercellular adhesion molecule 1 (ICAM-1) in large vascular endothelail.
Results:
1 General observation of behavior of all the rats
During the experiment, the normal rats grow well, have normal diet normal, and weight gain significantly. But the modle group showed apathetic, more drink, more food, polyuria, weight loss obviously and shape gradually thinner, color dry-taek and fluffy, the reaction retardation. Some even appeared hemiplegica, head tremor, cataracta and other symptoms. Two treatment groups showed a similar performance, but the performance of treatment groups alleviated than of the model group. There were two deaths in each group of model group and Western medicine group. Cause of the death was gavage, bites from each other, infection, and starvation.
2 The blood glucose and body weight of the rats in each group
Compared with the normal group, the blood glucose of the model group and two treatment groups was significantly higher (P<0.01), but the blood glucose of model group and Western medicine group was not of significant differences (P>0.05), the blood glucose of the traditional Chinese medicine group was significantly lower than model group (P<0.01).
Compared with the normal group, the body weight of the model group and two treatment groups decreased significantly (P<0.01). But the body weight of treatment groups was significantly higher (P<0.01) than the model group. The two treatment groups was not of significant differences (P>0.05).
3 The cholesterol (TC) and triglyceride (TG) changes of each group
The TC and TG of model group, traditional Chinese medicine group and Western medicine group were significantly higher than of normal group(P<0.05). Two treatment groups compared with the model group decreased significantly(P<0.05), but comparison between the two treatment groups had no significant difference(P>0.05).
4 Effect of Yiqiyangyinhuoyutongmaifang on experimental diabetic rats’large vascular endothelial morphology
The results showed that normal cell texture clear and take the normal shape, color uniform cytoplasm, flat artery endothelial cells, endometrial flat, smooth muscle cells(SMC) and elastic parallel plate order. Model rats’artery wall thickening of the endometrium appeared limitations, the smooth muscle cells in the film shallow proliferation mild, arranged in disorder, with lesions department interwoven arrangement, separation fracture. Rats’artery vascular endothelial morphology of the two control groups changed more lightly than the model group.
5 Effect of Yiqiyangyinhuoyutongmaifang on the expression of the intercellular adhesion molecule 1 (ICAM-1) in the diabetic rats’large vascular
Compared with normal group, the expression of the intercellular adhesion molecule 1 (ICAM-1) in the model rats’thoracic aortic endothelial cells was significantly higher than the normal group (P <0.01). After drug treatment, the treatment group compared with the model group, the expression of ICAM-1 was significantly reduced (P<0.05), the difference was statistically significant. The traditional Chinese medicine group compared with the western medicine group had no significant difference (P>0.05).
Conclusions:
1 Yiqiyangyinhuayutongluofang could be marked improve the histological lesions of diabetic rats’large vascular endothelial. It showed that Yiqiyangyinhuayutongluofang have a protective effect of the large vascular endothelial.
2 Yiqiyangyinhuayutongluofang can protect and cure diabetic macroangiopat- hy, which may be related to that it can improve lipid metabolism, reduce the blood glucose and the expression levels of intercellular adhesion molecule 1 (ICAM-1).
引文
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9张汝学,顾国明,张永祥,等.地黄低聚糖对实验性糖尿病及高血糖大鼠糖代谢的调节作用[J].中药药理研究与临床,1996,(1):14-17
10雷载权.中药学[M].上海科学技术出版社,1995,6:199
11杜冠华,张均田.丹参现代研究概况与进展[J].医药导报,2004,23(6):355-360
12 Ren DC, Du GH, Zhang JT. Inhibitory effect of salvianolic acids on the endothelial cells damage induced by hydrogen peroxide [J]. Chin J Pharm- acol Toxical,2003,17(5):333-337
13 Ren DC, Du GH, Zhang JT. Inhibitory effect of the watersoluble extract of Salvia miliorrhiza on neutrophile endothelial adhesion [J]. Jpn J Pharinaeo, 2002, 90(4):276-280
14 Ren DC, Du GH, Zhang JT. Effects of salvianolic acids on endothelial cells against damage induced by cholestance-3beta-5alpha-6beta-triol [J]. Chin Medical J, 2003,116(4):630-632
15成龙,梁日欣,杨滨,等.红花提取物对高血脂大鼠降脂和抗氧化的实验研究[J].中国实验方剂学杂志,2006,12(9):25-27
16曲莉,刘宗武,赵学忠.他汀类药物多效性研究进展[J].中国老年学杂志,2010,30(2):280-283
17 Forrester JS, Libby P. The inflammation hypothesis and its potential relevance to statin therapy [J]. Am J Cardio, 2007, 99(5): 732-738
18衡先培,朱章志,郑健.实用糖尿病中西医治疗[M].北京:人民军医出版社,2006,7:22
19吴艺捷.糖尿病大血管病变防治研究的新进展[J].临床荟萃,2000,15(2): 86-88
20雷载权.中药学[M].上海科学技术出版社,1995,6:206
21雷载权.中药学[M].上海科学技术出版社,1995,6: 301
22 Jun CD, Shimaoka M, Carman CV, et al. Dimerization and the effectiveness of ICAM-1 in mediating LFA-1-dependent adhesion[J].Proc Natl Acad Sci USA, 2001, 98: 6830-6835.
23李强翔,钟惠菊,周敏,等.葛根素对糖尿病大鼠血脂和主动脉细胞间粘附分子-1表达的调控[J].中国行为医学科学,2006,15(11):981-983
24卢曙芳,陈建悦,沈建国.细胞间粘附分子1与2型糖尿病大血管病变的关系[J].浙江预防医学,2007,19(5):59-61
25王翀,朱贤立,赵洪洋,等.弥漫性脑损伤大鼠脑组织细胞间粘附分子-1的表达与神经元损伤[J].中国行为医学科学,2006, 15: 14-16
1段尚仙,郑秀梅.活血化瘀法治疗糖尿病33例疗效观察[J].山西职工医学院报,1995,5(2):40-41
2林兰,张鸿恩,高齐健,等.降糖通脉饮胶囊治疗糖尿病血管合并症的临床研究[J].中医杂志,1992,33(8):26-28
3玉山江.林兰辨治糖尿病经验浅述[J].中华中医药杂志(原中国医药学报),2009, 24(10):1311-1313
4董振华.祝湛予治疗糖尿病经验举要[J].中国医药学报,1993,8(1):43-45
5李振中,尹翠梅.痰浊瘀血与糖尿病血管病变理论探讨[J].中西医结合心脑血管病杂志,2005,3(11):983-985
6张冰冰,杨宇峰.益气养阴活血解毒法治疗糖尿病大血管病变机制探讨[J].辽宁中医药大学学报,2008,10(11):31-33
7南征,高彦彬,钱秋海.糖尿病中西医综合治疗[M].北京:人民卫生出版社,2002:11-12
8季长春,程汉桥,董志,等.浅析糖尿病血管病变[J].中医药信息,2007,24(6): 40-42
9南征,高彦彬,钱秋海.糖尿病中西医结合治疗[M].北京:人民卫生出版社,2002:34
10周艳萍,张正浩.复方苦荞麦对糖尿病大鼠血管并发症早期防治的研究[J].辽宁中医药大学学报,2007,9(6):185-186
11周小青,罗尧岳,谢小兵,等.活血化瘀方对高脂饮食致家兔动脉粥样硬化的影响[J].中国中医药信息杂志,2004,11(5):401
12陈良,张梅,李长江.复方丹参滴丸对动脉粥样硬化粘附因子的作用[J].中国动脉硬化杂志,2007,15(2):101-103
13张红敏,陈世伟,谢春光,等.参芪复方抗自发性糖尿病GK大鼠早期动脉粥样硬化的作用机制[J].中国中药杂志,2006,31(15):1272-1276.
14马洪喜,李冬梅.黄芪皂苷对糖尿病大鼠血清激素水平的影响[J].微量元素与健康研究,2003,20(4):5-6
15王保华,欧阳静萍,刘永明,等.当归队高脂血清所致EVC304细胞损伤的保护作用[J].生理报,2001,53(3):240-243
16郝海平,许惠琴,朱荃,等.山茱萸环烯醚萜总苷对由链脲佐菌素诱导的糖尿病血管并发症大鼠血清sICAM-1、TNF-α的影响[J].中药药理与临床,2002,18(4):13-14
17柴可夫,周敏,杨明华,糖克软胶囊治疗糖尿病伴高黏滞血症的实验研究[J].中国实验方剂学杂志,2006,12(1):51-52
18姜德友,柳成刚,朴永植,等.糖心康对糖尿病大鼠心肌细胞凋亡促进与抑制因子基因表达的调控作用[J].时珍国医国药,2007,18(9):2114-2115
19黄霖,李迎新,刘华,等.活血降糖胶囊对动脉粥样硬化大鼠早期血管壁组织结构的影响[J].中国心血管病研究,2007,5(8):607-609
20高莹.辨证分型治疗糖尿病合并冠心病62例分析[J].中医药学刊,2003,2 (21):151
21李荣光.糖尿病性心脏病辨治体会[J].中国中医急症,2007,16(12):1548- 1550
2穆珺,史斌.高浓度葡萄糖对培养血管内皮细胞活力和黏附分子表达的影响[J].首都医科大学学报,2005,26(3):315-318
3周仲瑛.中医内科学[M].北京:中国中医药出版社,2003,1:433
4衡先培,朱章志,郑健.实用糖尿病中西医治疗[M].北京:人民军医出版社,2006,7:244-245
5李皓.雷米普利黄芪治疗糖尿病肾病的疗效观察[J].现代中西医结合杂志,2002,11(2):301
6马洪喜,李冬梅.黄芪皂苷对糖尿病大鼠血清激素水平的影响[J].微量元素与健康研究,2003,20(4):5-6
7雷载权.中药学[M].上海科学技术出版社,1995.6:302
8姚晓渝,杨勇,董福云.山茱萸不同工艺提取物的降血糖作用实验研究[J].北京中医,1997,(5):53-54
9张汝学,顾国明,张永祥,等.地黄低聚糖对实验性糖尿病及高血糖大鼠糖代谢的调节作用[J].中药药理研究与临床,1996,(1):14-17
10雷载权.中药学[M].上海科学技术出版社,1995,6:199
11杜冠华,张均田.丹参现代研究概况与进展[J].医药导报,2004,23(6):355-360
12 Ren DC, Du GH, Zhang JT. Inhibitory effect of salvianolic acids on the endothelial cells damage induced by hydrogen peroxide [J]. Chin J Pharm- acol Toxical,2003,17(5):333-337
13 Ren DC, Du GH, Zhang JT. Inhibitory effect of the watersoluble extract of Salvia miliorrhiza on neutrophile endothelial adhesion [J]. Jpn J Pharinaeo, 2002, 90(4):276-280
14 Ren DC, Du GH, Zhang JT. Effects of salvianolic acids on endothelial cells against damage induced by cholestance-3beta-5alpha-6beta-triol [J]. Chin Medical J, 2003,116(4):630-632
15成龙,梁日欣,杨滨,等.红花提取物对高血脂大鼠降脂和抗氧化的实验研究[J].中国实验方剂学杂志,2006,12(9):25-27
16曲莉,刘宗武,赵学忠.他汀类药物多效性研究进展[J].中国老年学杂志,2010,30(2):280-283
17 Forrester JS, Libby P. The inflammation hypothesis and its potential relevance to statin therapy [J]. Am J Cardio, 2007, 99(5): 732-738
18衡先培,朱章志,郑健.实用糖尿病中西医治疗[M].北京:人民军医出版社,2006,7:22
19吴艺捷.糖尿病大血管病变防治研究的新进展[J].临床荟萃,2000,15(2): 86-88
20雷载权.中药学[M].上海科学技术出版社,1995,6:206
21雷载权.中药学[M].上海科学技术出版社,1995,6: 301
22 Jun CD, Shimaoka M, Carman CV, et al. Dimerization and the effectiveness of ICAM-1 in mediating LFA-1-dependent adhesion[J].Proc Natl Acad Sci USA, 2001, 98: 6830-6835.
23李强翔,钟惠菊,周敏,等.葛根素对糖尿病大鼠血脂和主动脉细胞间粘附分子-1表达的调控[J].中国行为医学科学,2006,15(11):981-983
24卢曙芳,陈建悦,沈建国.细胞间粘附分子1与2型糖尿病大血管病变的关系[J].浙江预防医学,2007,19(5):59-61
25王翀,朱贤立,赵洪洋,等.弥漫性脑损伤大鼠脑组织细胞间粘附分子-1的表达与神经元损伤[J].中国行为医学科学,2006, 15: 14-16
1段尚仙,郑秀梅.活血化瘀法治疗糖尿病33例疗效观察[J].山西职工医学院报,1995,5(2):40-41
2林兰,张鸿恩,高齐健,等.降糖通脉饮胶囊治疗糖尿病血管合并症的临床研究[J].中医杂志,1992,33(8):26-28
3玉山江.林兰辨治糖尿病经验浅述[J].中华中医药杂志(原中国医药学报),2009, 24(10):1311-1313
4董振华.祝湛予治疗糖尿病经验举要[J].中国医药学报,1993,8(1):43-45
5李振中,尹翠梅.痰浊瘀血与糖尿病血管病变理论探讨[J].中西医结合心脑血管病杂志,2005,3(11):983-985
6张冰冰,杨宇峰.益气养阴活血解毒法治疗糖尿病大血管病变机制探讨[J].辽宁中医药大学学报,2008,10(11):31-33
7南征,高彦彬,钱秋海.糖尿病中西医综合治疗[M].北京:人民卫生出版社,2002:11-12
8季长春,程汉桥,董志,等.浅析糖尿病血管病变[J].中医药信息,2007,24(6): 40-42
9南征,高彦彬,钱秋海.糖尿病中西医结合治疗[M].北京:人民卫生出版社,2002:34
10周艳萍,张正浩.复方苦荞麦对糖尿病大鼠血管并发症早期防治的研究[J].辽宁中医药大学学报,2007,9(6):185-186
11周小青,罗尧岳,谢小兵,等.活血化瘀方对高脂饮食致家兔动脉粥样硬化的影响[J].中国中医药信息杂志,2004,11(5):401
12陈良,张梅,李长江.复方丹参滴丸对动脉粥样硬化粘附因子的作用[J].中国动脉硬化杂志,2007,15(2):101-103
13张红敏,陈世伟,谢春光,等.参芪复方抗自发性糖尿病GK大鼠早期动脉粥样硬化的作用机制[J].中国中药杂志,2006,31(15):1272-1276.
14马洪喜,李冬梅.黄芪皂苷对糖尿病大鼠血清激素水平的影响[J].微量元素与健康研究,2003,20(4):5-6
15王保华,欧阳静萍,刘永明,等.当归队高脂血清所致EVC304细胞损伤的保护作用[J].生理报,2001,53(3):240-243
16郝海平,许惠琴,朱荃,等.山茱萸环烯醚萜总苷对由链脲佐菌素诱导的糖尿病血管并发症大鼠血清sICAM-1、TNF-α的影响[J].中药药理与临床,2002,18(4):13-14
17柴可夫,周敏,杨明华,糖克软胶囊治疗糖尿病伴高黏滞血症的实验研究[J].中国实验方剂学杂志,2006,12(1):51-52
18姜德友,柳成刚,朴永植,等.糖心康对糖尿病大鼠心肌细胞凋亡促进与抑制因子基因表达的调控作用[J].时珍国医国药,2007,18(9):2114-2115
19黄霖,李迎新,刘华,等.活血降糖胶囊对动脉粥样硬化大鼠早期血管壁组织结构的影响[J].中国心血管病研究,2007,5(8):607-609
20高莹.辨证分型治疗糖尿病合并冠心病62例分析[J].中医药学刊,2003,2 (21):151
21李荣光.糖尿病性心脏病辨治体会[J].中国中医急症,2007,16(12):1548- 1550