CAJ | 학술논문

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（AT1 R）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AT1 R 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。
목적：관찰2형당뇨병（T2DM）대서신손상과정중혈관긴장소Ⅱ（AngⅡ）적표체，탐토통심락대당뇨병조기신소구고려과적영향급기작용궤제。방법：8주령 SD 웅성대서40지，채용고지사료＋저제량련뇨좌균소건립 T2DM대서모형，수궤분위공백조、모형조、힐사탄조（10 mg·kg －1·d －1）화통심락조（0．4 mg·kg －1·d －1），분별우4주화8주관찰 T2DM대서혈당（FBG）、뇨백단백배설솔（UAER）급신공능（Scr，BUN，Ccr）적변화；8주말차급약후취신조직，계산신중지수（KW／BW），채용 western blot 급 real time －PCR 기술검측 AngⅡ화 AngⅡ1형수체（AT1 R）단백화기인적표체。결과：T2DM대서적 FBG、UAER、Scr、BUN、Ccr 급 KW／BW 교공백조유불동정도적승고（P ＜0．05），통심락조 FBG 무명현변화（P＞0．05），기타각지표수평교모형조균현저강저（P ＜0．05）；WB 급 RT －PCR 결과현시통심락가이강저신조직중 AngⅡ화AT1 R 기인단백적과도표체（P ＜0．05）。결론：통심락가이개선 T2DM대서조기적고려과상태，억제뇨백단백적배설급신장비대，보호신공능；통심락가능시통과하조신조직중 AngⅡ적표체，억제이상활화적 RAS 래연완당뇨병신병적발생발전。
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.