银杏叶提取物治疗慢性肾小球肾炎的临床观察及相关实验研究
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摘要
慢性肾小球肾炎是由多种原因，多种病理类型组成的原发于肾小球的一组疾病，青壮年及儿童发病率较高。其临床特点是长期持续性尿异常，如蛋白尿及/或血尿，慢性进行性肾功能损害，可有高血压及/或水肿，最终发生固缩肾及终末期肾衰竭。慢性肾炎由于病程长，病因不清，与急性肾炎无肯定关系（大约只有10%左右有链球菌感染后急性肾炎史）；绝大多数慢性肾炎是其他原发性肾小球疾病直接迁延发展的结果，从而导致病程慢性化而肾单位不停顿地破坏。
慢性肾炎的发病机理目前已知的是①原由疾病的免疫炎症持续进行活动。②肾实质性高血压引起肾小动脉硬化。③肾小球血流动力学介导的肾小球硬化症。而导致肾小球的增生性、硬化性和膜性肾病。随着病程的进展，各原发肾小球疾病的病理学改变特点逐渐消失，代之以程度不等的肾小球硬化伴球囊缺血性改变及小血管硬化，相应肾单位萎缩，间质灶状纤维化。中医认为慢性肾炎病程长，病机复杂，正虚邪实是其主要病理基础，古有“久病入络”，“久病必瘀”之理论，主要病理改变是肺脾肾三脏俱损，阴阳气血失调，水液内停，气血郁而不行则成瘀，因湿致瘀，湿瘀互结。现代病理研究慢性肾炎主要是肾小球血流量减少，缺血，基底膜增厚、变性等，是一种变态反应性疾病。这与祖国医学“瘀血”，“血行不畅”相吻合。
在临床上，常用抗凝药有肝素和华法林，前者副作用较少且易于监测；若血管内已形成血块，则常采用尿激酶、链激酶和纤溶酶等溶栓剂，由于上述药物或多或少的存在副作用，且药物计量很难控制。因此，中药有效
成分提取物治疗CGN的血液高凝状态成为研究的热点。目前，丹参注射液、葛根注射液、灯盏花素等都是临床上用以改善CGN高凝状态的常用药物。银杏叶片是中药银杏叶的提取物，临床上主要用来治疗心、脑血管疾病，能有效地改善患者的血液流变学指标，降低血液粘滞度。但迄今为止经光盘文献检索，国内、外仅有少数几篇文章介绍银杏叶应用于肾炎，并且均不系统。本课题旨在观察银杏叶片对CGN在血液流变学、血脂、肾功能方面的影响，并探讨该药治疗CGN的血液高凝状态的作用机理。
本实验分为临床观察和实验研究两方面。在临床方面，选用吉林大学中日联谊医院中医科、肾风湿科住院病人54例，其中男 例，女 例，年龄18—59岁，平均年龄 岁，按照随机抽签分组原则分为治疗组和对照组。所有患者均符合中华内科杂志编委会肾脏病专业组1992年6月安徽太平会议拟定的慢性肾小球肾炎的诊断标准，均给予对症常规治疗。治疗组患者同时每天用银杏叶片38.4mg，每日3次，连续治疗21天，在治疗期间不用其他抗凝药物及抑制血小板聚集药。比较治疗组患者治疗前后血液流变学指标（BHV、BLV、ESR、PV）和两组患者治疗前后24h蛋白尿、肾功能（BUN、CRE）及血脂（CHO、TG）的变化。在动物实验方面，将48只健康雄性Wistar大鼠分为空白组（Ⅰ组）、造模组（Ⅱ组）、雷公藤治疗组（Ⅲ组）、银杏叶片低剂量治疗组（Ⅳ组）、银杏叶片中剂量治疗组（Ⅴ组）、银杏叶片高剂量治疗组（Ⅵ组），每组8只，按照Border方法复制C-BSA大鼠慢性肾炎模型，造模成功后，依照动物计量换算公式雷公藤多苷片治疗组每只每天按20mg/kg的雷公藤多苷片,银杏叶片组给予高（5.2mg/kg）、中（10.4 mg/kg）、低（20.8 mg/kg）剂量的银杏叶片,正常组与模型组给予等容量20ｍＬ/ｋｇ的生理盐水，连续给药21天。于实验20天各组大鼠取24小时尿做尿蛋白定量检查，之后将全部大鼠处死，腹主动脉取血，取肾脏进行病理学检查。所取血液进行血液流变学（BHV、BLV、PV）、血
小板聚集实验（ADP）、肾功能（同上）和血脂（CHO）检测，并比较各组指标变化是否有显著性差异。
实验结果表明：（1）银杏叶可改善CGN的血液高凝状态，无论是临床研究还是动物实验，经银杏叶片治疗后患者（大鼠）的血液流变学指标在BHV、BLV、PV、ADP均显著下降，经统计学处理 P＜0.01，P＜0.05 ，有显著性差异。（2）银杏叶片可降低CGN的蛋白尿，且银杏叶合并常规治疗的效果优于单纯常规治疗。临床观察显示治疗组经银杏叶片治疗前后24小时尿蛋白定量降低，统计学比较有显著性差异；和对照组有显著性差异，统计学处理P＜0.05。动物实验研究进一步表明，银杏叶与造模组比较24h尿蛋白定量降低，有显著性差异 P＜0.05 与雷公藤比较有显著性差异P＜0.05。（3）银杏叶片可降低血脂。（4）临床观察银杏叶可改善患者肾功能，统计学比较有显著性差异 P＜0.01，P＜0.05；动物实验大鼠肾功能无改变。通过上述实验可以看出银杏叶片不但可以改善CGN患者的血凝状态，而且可在一定程度上降低患者的蛋白尿，降低血脂，改善肾功能。
银杏树（Ginkgo bilobal）又称白果树，属落叶乔木，70.%分布在我国。银杏叶片是中药银杏叶的提取物，杏叶提取物（extract of Ginkgo biloba，EGB）的主要成分可分两大类：黄酮类和萜内酯类，黄酮类有效成分为黄酮甙，主要是山奈酚和槲皮素的葡萄糖鼠李糖甙。萜内酯化合物可再分为银杏内酯（Ginkgolinde）和白果内酯（bilobalid）。各类文献对EGB的药理研究证明，EGB可降低血液粘度，改善血液流变学使红细胞聚集性
Chronic glmerulonephritis (CGN )is a set of disease derived from glomerulus. It is caused by several reasons and consisted of many pathologies . The youngers and children’s incidence rate is higher than others. CGN’s clinical character is long term abnormal urina, for example: proteinuria and(or) hematuria, chronic progressing renal function damage, hypertension and(or) oedema, finally it will become contracted kindney and entire and final phase kidney porstration. Because CGN’s progress is long,the cause of disease is uncertain, there is no definite relationship between CGN and acute glmerulonephritis(only 10 percent or so have streptococcal infection and acute glmerulonephritis history),most of chronic glmerulonephritis are developed from other primary renal glomerular diseases, these reasons caused the progress chronicity and nephron is destroyed continuously.
The falling ill principles of CGN which is known now are the following: ①The immune inflammation of the original disease is active. ②renal substantial hypertension causes renal arteriolosclerosis. ③ Glomerulosclerosis which is mediated by
glomerular henmdynamics leads to the proliferative and sclerosing of glomerulus and membranous nephropathy. With the developing of the progress, the renal glomerular disease pathology alters its character and disappears gradually. And becomes aniso-degree glomerulosclerosis sacculus ischemia change and sclerosis of small blood vessels. The corresponding nephron dries up and shrinks. The renal interstitium becomes focal and fibrosis. Chinese medicine hold the view that CGN’s progress is long and the fall ill principle is complicated, zhengqi weak and xieqi strong is its main foundation of the fall ill principle. In ancient time there is the theory of “long time disease will enter luo”, “long time disease lead to blood clot”.The change of fall ill principle is the damage of the three visceras: the lung, the spleen and the kidney, the disproportion of negative and positive qi xue the disproportion, shui ye stayed inside, qi xue gastric stasis and become blood clot, moist leads to clot ,moist and clot congeal with each other. The modern pathology research of CGN mainly focus on the reduction of blood flow 、degeneration etc. It is a kind of allergic reactive disease. This is concide with Chinese medicine theory of “blood clot” and “xue xing bu chang”.
During the clinical, there are some ordinary anticoagulant medicines such as hepcine and warfarin because of their lower side effect and easily surveillance. If blood vessels have been clot by coagulatant, we always select UK.SK, but some of them have side effect for example: blooding, Sk also lead allergic reaction. So
active principle extract of Chinese herbs become the hot topic to treat blood viscosity of CGN. Now the injections of Saliva Miltiorrluza, Puerarin and fleabane are ordinary therapeatic medicine. Ginkgo Biloba, a natural extract, is the effective conposition of Chinese herbs.In clinical it mainly used in cardio-cerebral, and it can improve the patientes’ blood rheological index. But we only research few reports about the using of EGB in CGN, especially in mainland. This study is to observe the effect of how EGB treating the CGN’ s hyperviscosity and change of renal function and lipid metabolism. The study also will discuss the theory of EGB treating CGN’s blood viscosity.
This experiment includes clinical observation and experimental research. In clinical observation, there are 54 patients, including 32 men and 22 women, with the age averaging 41(18-59 years old). Who are selected from the Traditional Chinese Medical Department of Sino-Japanese Friendship Hospital of Ji Lin University Kidney Department. The patients are divided by two groups (therapeutic group and control group) according the random principle. All patients conform to the Diagnose Standard of the group of the renal disease of CGN in July, 1992. Two groups received the conservative treatment. The therapeutic group was given Tabel of Ginkgo Biloba 38.4mg,
慢性肾炎的发病机理目前已知的是①原由疾病的免疫炎症持续进行活动。②肾实质性高血压引起肾小动脉硬化。③肾小球血流动力学介导的肾小球硬化症。而导致肾小球的增生性、硬化性和膜性肾病。随着病程的进展，各原发肾小球疾病的病理学改变特点逐渐消失，代之以程度不等的肾小球硬化伴球囊缺血性改变及小血管硬化，相应肾单位萎缩，间质灶状纤维化。中医认为慢性肾炎病程长，病机复杂，正虚邪实是其主要病理基础，古有“久病入络”，“久病必瘀”之理论，主要病理改变是肺脾肾三脏俱损，阴阳气血失调，水液内停，气血郁而不行则成瘀，因湿致瘀，湿瘀互结。现代病理研究慢性肾炎主要是肾小球血流量减少，缺血，基底膜增厚、变性等，是一种变态反应性疾病。这与祖国医学“瘀血”，“血行不畅”相吻合。
在临床上，常用抗凝药有肝素和华法林，前者副作用较少且易于监测；若血管内已形成血块，则常采用尿激酶、链激酶和纤溶酶等溶栓剂，由于上述药物或多或少的存在副作用，且药物计量很难控制。因此，中药有效
成分提取物治疗CGN的血液高凝状态成为研究的热点。目前，丹参注射液、葛根注射液、灯盏花素等都是临床上用以改善CGN高凝状态的常用药物。银杏叶片是中药银杏叶的提取物，临床上主要用来治疗心、脑血管疾病，能有效地改善患者的血液流变学指标，降低血液粘滞度。但迄今为止经光盘文献检索，国内、外仅有少数几篇文章介绍银杏叶应用于肾炎，并且均不系统。本课题旨在观察银杏叶片对CGN在血液流变学、血脂、肾功能方面的影响，并探讨该药治疗CGN的血液高凝状态的作用机理。
本实验分为临床观察和实验研究两方面。在临床方面，选用吉林大学中日联谊医院中医科、肾风湿科住院病人54例，其中男 例，女 例，年龄18—59岁，平均年龄 岁，按照随机抽签分组原则分为治疗组和对照组。所有患者均符合中华内科杂志编委会肾脏病专业组1992年6月安徽太平会议拟定的慢性肾小球肾炎的诊断标准，均给予对症常规治疗。治疗组患者同时每天用银杏叶片38.4mg，每日3次，连续治疗21天，在治疗期间不用其他抗凝药物及抑制血小板聚集药。比较治疗组患者治疗前后血液流变学指标（BHV、BLV、ESR、PV）和两组患者治疗前后24h蛋白尿、肾功能（BUN、CRE）及血脂（CHO、TG）的变化。在动物实验方面，将48只健康雄性Wistar大鼠分为空白组（Ⅰ组）、造模组（Ⅱ组）、雷公藤治疗组（Ⅲ组）、银杏叶片低剂量治疗组（Ⅳ组）、银杏叶片中剂量治疗组（Ⅴ组）、银杏叶片高剂量治疗组（Ⅵ组），每组8只，按照Border方法复制C-BSA大鼠慢性肾炎模型，造模成功后，依照动物计量换算公式雷公藤多苷片治疗组每只每天按20mg/kg的雷公藤多苷片,银杏叶片组给予高（5.2mg/kg）、中（10.4 mg/kg）、低（20.8 mg/kg）剂量的银杏叶片,正常组与模型组给予等容量20ｍＬ/ｋｇ的生理盐水，连续给药21天。于实验20天各组大鼠取24小时尿做尿蛋白定量检查，之后将全部大鼠处死，腹主动脉取血，取肾脏进行病理学检查。所取血液进行血液流变学（BHV、BLV、PV）、血
小板聚集实验（ADP）、肾功能（同上）和血脂（CHO）检测，并比较各组指标变化是否有显著性差异。
实验结果表明：（1）银杏叶可改善CGN的血液高凝状态，无论是临床研究还是动物实验，经银杏叶片治疗后患者（大鼠）的血液流变学指标在BHV、BLV、PV、ADP均显著下降，经统计学处理 P＜0.01，P＜0.05 ，有显著性差异。（2）银杏叶片可降低CGN的蛋白尿，且银杏叶合并常规治疗的效果优于单纯常规治疗。临床观察显示治疗组经银杏叶片治疗前后24小时尿蛋白定量降低，统计学比较有显著性差异；和对照组有显著性差异，统计学处理P＜0.05。动物实验研究进一步表明，银杏叶与造模组比较24h尿蛋白定量降低，有显著性差异 P＜0.05 与雷公藤比较有显著性差异P＜0.05。（3）银杏叶片可降低血脂。（4）临床观察银杏叶可改善患者肾功能，统计学比较有显著性差异 P＜0.01，P＜0.05；动物实验大鼠肾功能无改变。通过上述实验可以看出银杏叶片不但可以改善CGN患者的血凝状态，而且可在一定程度上降低患者的蛋白尿，降低血脂，改善肾功能。
银杏树（Ginkgo bilobal）又称白果树，属落叶乔木，70.%分布在我国。银杏叶片是中药银杏叶的提取物，杏叶提取物（extract of Ginkgo biloba，EGB）的主要成分可分两大类：黄酮类和萜内酯类，黄酮类有效成分为黄酮甙，主要是山奈酚和槲皮素的葡萄糖鼠李糖甙。萜内酯化合物可再分为银杏内酯（Ginkgolinde）和白果内酯（bilobalid）。各类文献对EGB的药理研究证明，EGB可降低血液粘度，改善血液流变学使红细胞聚集性
Chronic glmerulonephritis (CGN )is a set of disease derived from glomerulus. It is caused by several reasons and consisted of many pathologies . The youngers and children’s incidence rate is higher than others. CGN’s clinical character is long term abnormal urina, for example: proteinuria and(or) hematuria, chronic progressing renal function damage, hypertension and(or) oedema, finally it will become contracted kindney and entire and final phase kidney porstration. Because CGN’s progress is long,the cause of disease is uncertain, there is no definite relationship between CGN and acute glmerulonephritis(only 10 percent or so have streptococcal infection and acute glmerulonephritis history),most of chronic glmerulonephritis are developed from other primary renal glomerular diseases, these reasons caused the progress chronicity and nephron is destroyed continuously.
The falling ill principles of CGN which is known now are the following: ①The immune inflammation of the original disease is active. ②renal substantial hypertension causes renal arteriolosclerosis. ③ Glomerulosclerosis which is mediated by
glomerular henmdynamics leads to the proliferative and sclerosing of glomerulus and membranous nephropathy. With the developing of the progress, the renal glomerular disease pathology alters its character and disappears gradually. And becomes aniso-degree glomerulosclerosis sacculus ischemia change and sclerosis of small blood vessels. The corresponding nephron dries up and shrinks. The renal interstitium becomes focal and fibrosis. Chinese medicine hold the view that CGN’s progress is long and the fall ill principle is complicated, zhengqi weak and xieqi strong is its main foundation of the fall ill principle. In ancient time there is the theory of “long time disease will enter luo”, “long time disease lead to blood clot”.The change of fall ill principle is the damage of the three visceras: the lung, the spleen and the kidney, the disproportion of negative and positive qi xue the disproportion, shui ye stayed inside, qi xue gastric stasis and become blood clot, moist leads to clot ,moist and clot congeal with each other. The modern pathology research of CGN mainly focus on the reduction of blood flow 、degeneration etc. It is a kind of allergic reactive disease. This is concide with Chinese medicine theory of “blood clot” and “xue xing bu chang”.
During the clinical, there are some ordinary anticoagulant medicines such as hepcine and warfarin because of their lower side effect and easily surveillance. If blood vessels have been clot by coagulatant, we always select UK.SK, but some of them have side effect for example: blooding, Sk also lead allergic reaction. So
active principle extract of Chinese herbs become the hot topic to treat blood viscosity of CGN. Now the injections of Saliva Miltiorrluza, Puerarin and fleabane are ordinary therapeatic medicine. Ginkgo Biloba, a natural extract, is the effective conposition of Chinese herbs.In clinical it mainly used in cardio-cerebral, and it can improve the patientes’ blood rheological index. But we only research few reports about the using of EGB in CGN, especially in mainland. This study is to observe the effect of how EGB treating the CGN’ s hyperviscosity and change of renal function and lipid metabolism. The study also will discuss the theory of EGB treating CGN’s blood viscosity.
This experiment includes clinical observation and experimental research. In clinical observation, there are 54 patients, including 32 men and 22 women, with the age averaging 41(18-59 years old). Who are selected from the Traditional Chinese Medical Department of Sino-Japanese Friendship Hospital of Ji Lin University Kidney Department. The patients are divided by two groups (therapeutic group and control group) according the random principle. All patients conform to the Diagnose Standard of the group of the renal disease of CGN in July, 1992. Two groups received the conservative treatment. The therapeutic group was given Tabel of Ginkgo Biloba 38.4mg,
引文
[1] 叶任高.现代肾脏病治疗学[M].南昌:江西科学技术出版社.2000年10月第一版:317—324.
[2] 江波。清热养血活血法治疗慢性肾炎血尿27例[J]。湖北中医杂志，2001，23（12）：29。
[3] 汪钟。活血化瘀中药对血小板功能调节的机理[J]。中国中西医结合杂志，1992，12（9）：567-570。
[4] 朱陵群，黄启福，魏民，等。川芎嗪对家兔膜性肾炎时血小板功能的影响[J]。中国病理生理杂志，1995，11（4）：382-386
[5]KleijinenJ,KnipachildP.Gingkgobiloba.Lancet,1992,340(7):1136.
[6]Pincernail J,Depuis M,Nasr C,et al.Superoxide anion scavenging effect and superoxide istriutase activity of ginkgo biloba extract.Experientia,1989,45(8):708-712.
[7] Marexxci L,Maguite JJ,Droy-Leaix MT,et al.The nitric oxidescavenging properties of EGB761.Riccbem Biophs Res Commun,1994,20(2):748-755.
[8] 康辉，黄矛。银杏叶提取物药理学研究概况[J]。医药学实验杂志，2002，20（6）：334-228。
[9] 刘颖。银杏叶提取物的药理作用及临床应用[J]。天津医药，2000，12（4）：38-39。
[10] Border W A.Induction of membranous nephropathy in rabbits by administration of an exogenous cationic dntigen[J].J Clin Invest, 1982,69:451.
[11] Hricik DE，Chung-park M，Sedor JR．Glomerulonephritis．N Engl J Med，1998；339：888
[12] Savill J，Mooney A，Hughes J．Apoptosis and renal scarring．Kidney Int，1996；54（Suppl）：S14。
[13] 王海燕.肾脏病学[M].第2版.北京:北京人民卫生出版社996.494-501.
[14] Moreau J P,Eck C R,Cabe J M..Absorption,distribution and limination of radio labeled ginkgo biloba leaves extract sintherat .Presse Med, 1986,
15(31):1458.
[15] Kleijnen J,Knipschild P,Ginkogo biloba, 1992,340(7):1136.
[16] 凌一揆。中药学[M]。第1版。上海：上海科学技术出版社187。
[17] Oyama Y,Chilkahisa L,ToshilioU,et al.Gingko biloba extract protects brain neurons against oxidative stress induced ba hydrogen peroxide [J].Brain Res,1996,712;349。
[18] 严萍萍. 内皮素与冠心病[J]. 心血管病进展, 1993, 14 (6) : 330.
[19] 耿秀芳, 李桂芝, 康 白,等。银杏叶总黄酮对缩血管物质活性的影响[J]。维纺医学院学报，2000，22（3）：192-193
[20] 王筠默。 银杏叶的药理研究[J]。中草药，1998，29（增刊）：9。
[21] Cheung F,Siow YL and O K .Inhibition ba ginkgolides and bilobalide of the production of nitric oxide in macrophages(THP-1)but not in endothelial cells(HUVED)[J].Biochem Pharmacol,2001,61(4):503-510.
[22] 蒋季杰，范亚平。现代肾病学[M]。第1版。北京：人民军医出版社149。
[23] 耿秀芳，孙晓丽，王洪刚，等。银杏叶总黄酮降压作用的实验与临床研究[J]。中国中药杂志，2002，27（8）：606-608。
[24] 贾 敏。血竭总黄酮对实验性静脉血栓及体外血小板聚集的抑制作用[J]。中药药理与临床，2000，16（3）。18-19。
[25] Braquet P.touqui L ,Sheng TY,et al.Perspectives in platelet-activating factor research[J].J Pharmacol Rev,1987,39(2):97.
[26] Landolfi R,Mower RT,Steiner M.Modification of piatelet function and arachidonic acid metabolism by bioflavonoids tructureactivityrelations[J].
BiochPharmacol,1984,33(9):1525.
[27] 袁 霞，王 宁，孙玉华。肝素加中药活血化瘀治疗慢性肾炎顽固性蛋白尿26 例[J]。新疆中医药，2003，21（3）：18-19。
[28] 刘久波，陈林，杨道华，等。银杏叶制剂、丹参对急性肾功能衰竭家兔血液流变学的影响[J]。微循环学杂志，2002，12（3）：3-5。
[29] Bernarol DB.Extrarenal complieations of the nephropic syndrome
[J].Kidney Int,1988,(33),1184.
[30] Carber DW,Coulibieb et al.Catabolism of very low density ipoproteins
in experimental nephrosis [J].Clin Invest,1984,(77):1375.
[31] 柳韶真，胡杰。银杏叶片治疗高脂血症的临床分析[J]。河南实用神经病学杂志，2003，6（1）：77。
[2] 江波。清热养血活血法治疗慢性肾炎血尿27例[J]。湖北中医杂志，2001，23（12）：29。
[3] 汪钟。活血化瘀中药对血小板功能调节的机理[J]。中国中西医结合杂志，1992，12（9）：567-570。
[4] 朱陵群，黄启福，魏民，等。川芎嗪对家兔膜性肾炎时血小板功能的影响[J]。中国病理生理杂志，1995，11（4）：382-386
[5]KleijinenJ,KnipachildP.Gingkgobiloba.Lancet,1992,340(7):1136.
[6]Pincernail J,Depuis M,Nasr C,et al.Superoxide anion scavenging effect and superoxide istriutase activity of ginkgo biloba extract.Experientia,1989,45(8):708-712.
[7] Marexxci L,Maguite JJ,Droy-Leaix MT,et al.The nitric oxidescavenging properties of EGB761.Riccbem Biophs Res Commun,1994,20(2):748-755.
[8] 康辉，黄矛。银杏叶提取物药理学研究概况[J]。医药学实验杂志，2002，20（6）：334-228。
[9] 刘颖。银杏叶提取物的药理作用及临床应用[J]。天津医药，2000，12（4）：38-39。
[10] Border W A.Induction of membranous nephropathy in rabbits by administration of an exogenous cationic dntigen[J].J Clin Invest, 1982,69:451.
[11] Hricik DE，Chung-park M，Sedor JR．Glomerulonephritis．N Engl J Med，1998；339：888
[12] Savill J，Mooney A，Hughes J．Apoptosis and renal scarring．Kidney Int，1996；54（Suppl）：S14。
[13] 王海燕.肾脏病学[M].第2版.北京:北京人民卫生出版社996.494-501.
[14] Moreau J P,Eck C R,Cabe J M..Absorption,distribution and limination of radio labeled ginkgo biloba leaves extract sintherat .Presse Med, 1986,
15(31):1458.
[15] Kleijnen J,Knipschild P,Ginkogo biloba, 1992,340(7):1136.
[16] 凌一揆。中药学[M]。第1版。上海：上海科学技术出版社187。
[17] Oyama Y,Chilkahisa L,ToshilioU,et al.Gingko biloba extract protects brain neurons against oxidative stress induced ba hydrogen peroxide [J].Brain Res,1996,712;349。
[18] 严萍萍. 内皮素与冠心病[J]. 心血管病进展, 1993, 14 (6) : 330.
[19] 耿秀芳, 李桂芝, 康 白,等。银杏叶总黄酮对缩血管物质活性的影响[J]。维纺医学院学报，2000，22（3）：192-193
[20] 王筠默。 银杏叶的药理研究[J]。中草药，1998，29（增刊）：9。
[21] Cheung F,Siow YL and O K .Inhibition ba ginkgolides and bilobalide of the production of nitric oxide in macrophages(THP-1)but not in endothelial cells(HUVED)[J].Biochem Pharmacol,2001,61(4):503-510.
[22] 蒋季杰，范亚平。现代肾病学[M]。第1版。北京：人民军医出版社149。
[23] 耿秀芳，孙晓丽，王洪刚，等。银杏叶总黄酮降压作用的实验与临床研究[J]。中国中药杂志，2002，27（8）：606-608。
[24] 贾 敏。血竭总黄酮对实验性静脉血栓及体外血小板聚集的抑制作用[J]。中药药理与临床，2000，16（3）。18-19。
[25] Braquet P.touqui L ,Sheng TY,et al.Perspectives in platelet-activating factor research[J].J Pharmacol Rev,1987,39(2):97.
[26] Landolfi R,Mower RT,Steiner M.Modification of piatelet function and arachidonic acid metabolism by bioflavonoids tructureactivityrelations[J].
BiochPharmacol,1984,33(9):1525.
[27] 袁 霞，王 宁，孙玉华。肝素加中药活血化瘀治疗慢性肾炎顽固性蛋白尿26 例[J]。新疆中医药，2003，21（3）：18-19。
[28] 刘久波，陈林，杨道华，等。银杏叶制剂、丹参对急性肾功能衰竭家兔血液流变学的影响[J]。微循环学杂志，2002，12（3）：3-5。
[29] Bernarol DB.Extrarenal complieations of the nephropic syndrome
[J].Kidney Int,1988,(33),1184.
[30] Carber DW,Coulibieb et al.Catabolism of very low density ipoproteins
in experimental nephrosis [J].Clin Invest,1984,(77):1375.
[31] 柳韶真，胡杰。银杏叶片治疗高脂血症的临床分析[J]。河南实用神经病学杂志，2003，6（1）：77。