化瘀通络中药对糖尿病肾病大鼠肾皮质血管紧张素转化酶2-血管紧张素(1-7)-Mas轴的影响  

Effect of Chinese Herbs for Stasis Removing and Collaterals Dredging upon Angiotensin-Converting Enzyme 2-Angiotensin-( 1-7) -Mas Axis in the Renal Cortex of Diabetic Nephropathy Rats

作　　者：徐晶[1] 马二卫 白璐[1] 马赟[1] 郭倩[1] 贾蕊[1] 张江华[1] 陈志强[1] 

机构地区：[1]河北医科大学中西医结合研究所,石家庄050017

出　　处：《中国中西医结合杂志》2014年第6期714-721,共8页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金资助项目(No.81173419)

摘　　要：目的观察化瘀通络中药对糖尿病肾病大鼠肾皮质血管紧张素转化酶2-血管紧张素(1-7)-Mas[ACE2-Ang-(1-7)-Mas]轴的影响。方法将89只雄性SD大鼠按随机数字表法分为空白对照组(C组,22只)、高糖高脂对照组(H组,10只)和1%链尿佐菌素(streptozotocin,STZ)注射组(57只)。STZ注射组以高糖高脂饲料联合腹腔注射STZ制备糖尿病模型(50只),再分为模型组(M组,24只)、厄贝沙坦组(I组,13只)和化瘀通络中药组(Z组,13只)。I组和Z组大鼠分别给予厄贝沙坦和化瘀通络中药混悬液灌胃,共16周,其余各组给予等体积饮用水。检测各组大鼠4个时间点的血糖和24 h尿蛋白定量,分别采用实时荧光定量PCR(Real-time PCR)、免疫组化法、蛋白印迹(Western blot)方法检测不同时间点各组肾皮质ACE2、Mas蛋白的表达变化,第16周末对各组肾皮质2种蛋白表达进行定量分析。结果与C组比较,H、M组血糖均升高,且M组高于H组(P<0.01)。不同时间点24 h尿蛋白与C组比较,M组升高,且M组高于H组(P<0.05)。与M组比较,I组8周末和Z组8、16周末均降低(P<0.05),且第16周末Z组优于I组(P<0.05)。与C、H两组比较,M组第16周末肾皮质ACE2 mRNA的表达降低(P<0.01);与M组比较,Z组表达升高(P<0.01)。与C组比较,M组第16周末Mas mRNA的表达差异无统计学意义(P>0.05);与H组比较,M组表达降低(P<0.05);与M组比较,Z组表达升高(P<0.05),且高于I组(P<0.05)。M组ACE2、Mas蛋白表达的定量随时间呈递减趋势。第16周末ACE2、Mas蛋白的表达定量,与C组比较,M组两者表达均降低(P<0.05);与M组比较,Z组ACE2的表达和I、Z两组Mas的表达均升高(P<0.05)。结论化瘀通络中药可能通过上调ACE2、Mas mRNA及其蛋白的表达,促进ACE2-Ang-(1-7)-Mas轴发挥作用,降低尿蛋白,对糖尿病肾病大鼠起到肾保护的作用。Objective To observe the effect of Chinese herbs for stasis removing and collaterals dredging （CHSRCD） upon angiotensin-converting enzyme 2-angiotensin-（1-7）-Mas axis in the renal cortex of diabetic nephropathy rats. Methods Totally 89 male Sprague-Dawley rats were randomly divided into the blank control group （C group, n =22）, the high-glucose high-fat control group （H group, n =10）, and the streptozotocin （STZ）-injecting group （n =57）. The diabetes rat model （n =50） was induced by feeding high-glucose high-fat diet in combination with intraperitoneal injection of STZ, which were further divided into the model group （M group, n =24）, the irbesartan group （I group, n =13）, and the CHSRCD （Z group, n =13）. Rats in I and Z groups were intragastrically fed with suspension of irbesartan and CHSRCD, once daily for 16 weeks. Equal volume of drinking water was administrated to rats in the rest groups. Blood glu- cose and 24 h urine protein quantitation were tested at four time points. And the mRNA expression of ACE2 and Mas at various time points was detected by Real-time PCR, immunohistochemical assay, and Western blot. Quantitative analyses of ACE2 and Mas protein expression were performed at the end of week 16. Results Compared with the C group, blood glucose increased in the H and M groups （P 〈0.01 ）. It was higher in the H group （P 〈0.01 ）. 24 h urine protein quantitation at different time points increased in the M group, and it was higher than that in the H group （P 〈0. 05）. Compared with the M group, 24 h urine protein quantitation decreased at the end of week 8 in the I group, and at the end of week 8 and 16 in the Z group （P 〈0. 05）. It was lower in the Z group than in the I group at the end of week 16 （P 〈0.05）. Compared with the C and H groups, the expression of ACE2 mRNA in the renal cortex was lower in the M group at the end of week 16 （P 〈0. 01 ）. Compared with the M group, it was higher in the Z group （P 〈0. 01 ）. There was

关 键 词：糖尿病肾病 化瘀通络 血管紧张素转化酶2 MAS 

分 类 号：R285.5[医药卫生—中药学]