厄贝沙坦联合雷公藤甲素对2型糖尿病大鼠肾脏ANGPTL2、VEGF表达影响

目的：观察厄贝沙坦联合雷公藤甲素（TP）对ANGPTL2、VEGF在2型糖尿病（T2DM）大鼠肾脏表达的影响并探讨其机制.方法：50只SD雄性大鼠随机分为正常对照组（NC,10只）和实验组（40只）,实验组给予高糖高脂喂养联合小剂量链脲佐菌素（STZ 30 mg/kg）建立T2DM大鼠模型,再随机分为4组：糖尿病对照组（DM）、厄贝沙坦组（DI）、雷公藤甲素组（DT）及厄贝沙坦联合雷公藤甲素组（DIT）.药物干预8周后,测体重、血压、肾重、血糖、血肌酐（Scr）、尿素氮（BUN）,24 h尿蛋白（UAL）的排泄量;镜下观察肾组织病理改变;免疫组化显色技术及实时定量PCR检测血管生成素样蛋白2（ANGPTL2）、血管内皮生长因子（VEGF）表达的变化.结果：DM组与NC组相比血糖、肌酐、BUN及UAL明显升高（P〈0.01）,实时定量PCR示ANGPTL2、VEGF mRNA 明显上调（P〈0.01 ）;与DM组相比较,DT、DI及DIT组血糖、肌酐、BUN及UAL明显降低（P＜0.01）,DT、DI组中ANGPTL2、VEGF mRNA表达下调,DIT组更为明显（P〈0.05）.结论：ANGPTL2、VEGF在T2DM大鼠肾脏中的表达上调,厄贝沙坦及雷公藤甲素可降低ANGPTL2及VEGF在T2DM大鼠肾脏中的表达,并有协同作用.

Influence of Irbesrtan Combined with Triptolide on ANGPTL2 and VEGF in the Kidney of 2 Type Diabetes Rat Models

Objective：To observe the effect of irbesartan combined with triptolide on ANGPTL2 and VEGF in the kidney of 2 type diabetes（T2DM） rat models, and discuss its mechanism. Methods： 50 SD male rats were divided into normal control group （NC,n = 10） and experimental group （n =40） randomly . The experimental group was fed with high sugar -fat diet and given a low dose streptozocin（STZ 30 mg/kg） established type 2 diabetic model rats, and then randomly divided into 4 groups：diabetes control group （DM） ,irbesrtan group（DI） ,triptolide group（DT） and irbesartan combined with triptolide group （DIT）. Weight, blood pres- sure, blood glucose, serum creatinine（ Scr）, blood urea nitrogen（ BUN）, 24 hour urinary albumin（ （UAL） and renal histomorphology were observed after Drug intervention for 8 weeks, the expression of angiotensin - like protein 2 （ ANGPTL2）, vascular endothelial growth factor（VEGF） in renal tissue were detected by immunohistochemisty and real -time PCR. Results：blood glucose, serum creati- nine, BUN and UAL in DM group were obviously higher than those of the NC group （P 〈0.01 ） ,and the mRNA of ANGPTL2 and VEGF distantly upregulated compared with NC group （P 〈 0.01 ） ; Meanwhile blood glucose, serum creatinine and BUN and UAL in DI,DT and DIT group were significantly lower（P 〈0.01 ）compared to DM group,and the mRNA of ANGPTL2 and VEGF downregu- lated. Neverthless, in irbesrtan combined with triptolide group the changes of those indexes above were more significant than those in DI group or in DT group （ P 〈 0.05 ）. Conclusion： These results indicate that the expression of ANGPTL2, VEGF in kidney tissue of T2DM rats were upregulated ;irbesartan and triptolide could decrease ANGPTL2 ,VEGF,and they have synergistic effect.