芪蛭降糖胶囊对糖尿病肾病大鼠肾组织血管内皮细胞生长因子及细胞外基质的影响  

Effects of Qizhi Jiangtang Capsule on Vascular Endothelial Growth Factor and Extracellular Matrix of Kidney in Diabetic Nephropathy Rats

作　　者：孟凡辰[1] 郭兆安[2] 于春江 孙春晓[1] 武帅[1] 袁婷[1] 李悦[1] 贾佑铎 

机构地区：[1]山东中医药大学,济南250011 [2]山东中医药大学附属医院,山东省中医院,济南250011 [3]吉林省博士后科研创业基地,四平136001

出　　处：《中国中西医结合肾病杂志》2014年第8期676-681,I0001,I0002,共8页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：山东省2013~2014年度中医药科技发展计划项目(No.2013ZDZK-027)

摘　　要：目的：观察芪蛭降糖胶囊对糖尿病肾病（diabetic nephropathy，DN）大鼠肾组织血管内皮细胞生长因子（vascu-lar endothelial growth factor，VEGF）及细胞外基质（extracellular matrix，ECM）的影响。方法：清洁级6-7周龄雄性 Wister 大鼠48只，按体重随机取40只，采用切除右肾加腹腔注射链脲佐菌素（strephozotocin，STZ）的方法制备 DN 模型。模型成功后按照血糖高低排序，两头抽取随机分为模型组、缬沙坦对照组（简称对照组）、芪蛭降糖胶囊低剂量组、芪蛭降糖胶囊高剂量组，每组10只大鼠。另取8只正常大鼠行右肾假切除术，腹腔注射等量柠檬酸缓冲液作为假手术组。成模2 d 起各组给予相应浓度和剂量的药物灌胃，分别于4周、8周观察血肌酐（Scr）、尿素氮（BUN）、血清胱抑素- C（Cystatin - C）、β2-微球蛋白（β2- MG）、24 h 尿蛋白定量（24 h TP）、尿微量白蛋白（mAlb）、尿微量白蛋白/尿肌酐（UmAlb/ Ucr）。8周后处死动物，肾组织行 HE 染色，光镜下观察肾组织病变，电镜下观察肾组织足细胞的变化。免疫组化检测 VEGF、基质金属蛋白酶9（MMP -9）、基质金属蛋白酶抑制因子-1（TIMP -1）、纤维黏连蛋白（FN）、Ⅳ型胶原蛋白（ColⅣ）的表达。结果：在各个时间点，模型组大鼠血 Scr、BUN、Cystatin - C、β2- MG，尿24 h TP、mAlb、UmAlb/ Ucr 均明显高于假手术组（P ﹤0．05），对照组明显低于模型组（P ﹤0．05），中药组显著低于对照组和模型组，且呈剂量依赖关系（P ﹤0．05-0．01）。与模型组和对照组相比，HE 染色显示芪蛭降糖胶囊能减轻 DN 大鼠肾组织及其血管病理损害。电镜观察显示，芪蛭降糖胶囊能明显减轻 DN 大鼠肾组织基底膜增厚、内皮细胞及系膜增生，减轻足细胞足突融合，且呈剂量依赖关系。免疫组化显示 VEGF、TIMP -1、FN、ColⅣ在模型组的表达较假手术组Objective：To Study effects of Qizhi Jiangtang Capsule（QJC）on the expressions of VEGF and ECM in kidney tissues of DN rats. Methods：40 of the 48 male Wistar rats（6 to 7 weeks）were randomly divided into 4 groups：the sham operation group,the model group,the Valsartan group（control group）,the low dosage of QJC granules group（low dosage group）and high dosage of QJC granules group（high dosage group）,and each group with 10 rats. Except the rats of the sham operation group,the other rats were established DN animal model by removaling the right kidney with intraperitoneal injection of STZ. Medicine was given to each group according to the designed concentration and dosage after 2 days of the model established. Serum creatinine. blood urea nitrogen,cystatin - C,β2 - microglobulin,24 hour surinary protein quantitative,urine microalbumin and UmALB/ Ucr of DN rats were tested and recorded every 4 weeks. All animals were put to death after being treated 8 weeks. Histological change in the kidney tissues was examined by HE stain. Kidney tissue was observed under optical microscope. Kidney podocyte was observed under elec-tron microscope. VEGF,Matrix Metalloproteinase 9（MMP - 9）,Matrix Metalloproteinases Inhibitory Factor1（TIMP - 1）,fibronec-tin（FN）andⅣType Collagen（ColⅣ）were detected by immunohistochemical. Results：At all time points,Scr,BUN,Cystatin - C,β2 - MG,24 h TP,mALB and UmALB/ Ucr of the model group were higher than those of the sham operation group（P ﹤ 0. 05）,the control group was lower than the model group（P ﹤ 0. 05）,the QJC groups were higher than the sham operation group with dose de-pendent（P ﹤ 0. 05 ~ 0. 01）. Compared with the model group and control group,HE staining showed that kidney and vessel pathologi-cal damage of DN rats were lessened by QJC. Observations of electron microscopy show that kidney thickening of basement membrane, endothelial cell and mesangial proliferation can obviously be relieved by QJC,podocyte foot process fusion also c

关 键 词：芪蛭降糖胶囊 糖尿病肾病 血管内皮生长因子 细胞外基质 

分 类 号：R285.5[医药卫生—中药学]