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作 者:李娇阳[1,2] 高彦彬[1,2] 周盛楠[1,2] 邹大威[1] 朱智耀[1] 张娜[1] 王馨瑶[1] 崔方强 刘静[1]
机构地区:[1]首都医科大学中医药学院,北京100069 [2]中医络病研究北京市重点实验室,北京100069
出 处:《世界中医药》2015年第8期1222-1226,共5页World Chinese Medicine
基 金:国家重点基础研究发展计划课题("973"计划)(编号:2012CB518602)
摘 要:目的:观察2型糖尿病(T2DM)大鼠肾损伤过程中血管紧张素Ⅱ(AngⅡ)的表达,探讨通心络对糖尿病早期肾小球高滤过的影响及其作用机制。方法:8周龄SD雄性大鼠40只,采用高脂饲料+低剂量链脲佐菌素建立T2DM大鼠模型,随机分为空白组、模型组、缬沙坦组(10 mg·kg-1·d-1)和通心络组(0.4 mg·kg-1·d-1),分别于4周和8周观察T2DM大鼠血糖(FBG)、尿白蛋白排泄率(UAER)及肾功能(Scr,BUN,Ccr)的变化;8周末次给药后取肾组织,计算肾重指数(KW/BW),采用western blot及real time-PCR技术检测AngⅡ和AngⅡ1型受体(AT1R)蛋白和基因的表达。结果:T2DM大鼠的FBG、UAER、Scr、BUN、Ccr及KW/BW较空白组有不同程度的升高(P<0.05),通心络组FBG无明显变化(P>0.05),其他各指标水平较模型组均显著降低(P<0.05);WB及RT-PCR结果显示通心络可以降低肾组织中AngⅡ和AT1R基因蛋白的过度表达(P<0.05)。结论:通心络可以改善T2DM大鼠早期的高滤过状态,抑制尿白蛋白的排泄及肾脏肥大,保护肾功能;通心络可能是通过下调肾组织中AngⅡ的表达,抑制异常活化的RAS来延缓糖尿病肾病的发生发展。Objective:To observe the renal angiotensin Ⅱ expression in type 2 diabetic rats,to investigate the effect and the possi-ble mechanism of Tongxinluo on glomerular hyperfiltration in early diabetes.Methods:The rat model of type 2 diabetes mellitus was induced by injection of low-dose of streptozocin after having high-fat diet for 4 weeks,and they were randomly divided into 4 groups—normal group,diabetic group,valsartan treated group (1 0 mg·kg -1 ·d -1 )and Tongxinluo treated group(0.4 mg· kg -1 ·d -1 );the level of fasting blood glucose(FBG),urinary albumin excretion rate(UAER)and the renal function included se-rum creatinine(Scr),blood urea nitrogen(BUN)and creatinine clearance rate (Ccr)were measured every 4 weeks;After 8 weeks,kidney weight/body weight ratio(KW/BW)was calculated and the renal expression of angiotensin Ⅱ and angiotensin Ⅱtype 1 receptor(AT1 R)was determined by western blot and real-time PCR.Results:The level of UAER,Scr,BUN,Ccr,KW/BW,AngⅡand AT1 R expression in Tongxinluo treated group was lower than it in diabetic group(P 〈0.05)while FBG had no significant alteration(P 〉0.05).Conclusion:Tongxinluo can improve glomerular hyperfiltration,urinary albumin excretion,kid-ney hypertrophia and the renal function in type 2 diabetic rats.The mechanism could be related to inhibition of AngⅡand AT1 R expression.
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