三七总苷对糖尿病大鼠早期肾脏高滤过及血管内皮功能的影响

Effect of Panax Notoginoside on the Glomerular Hyperfiltration and Function of Vascular Endothelium in Rats with Experimental Diabetes in Its EarlyStage

目的观察三七总苷对糖尿病大鼠早期肾脏高滤过及血管内皮功能的影响,探讨三七总苷对糖尿病肾病的治疗作用及其机制。方法采用高脂饲料喂养加尾静脉注射链脲佐菌素(STZ)建立2型糖尿病大鼠模型。将50只大鼠随机分成5组,每组各10只。正常组、糖尿病模型组给予等量消毒自来水灌胃,三七总苷低剂量组(100mg·kg1·d1)、三七总苷高剂量组(200mg·kg1·d1)、卡托普利组(50mg·kg1·d1)均连续灌胃12周。检测各组动物空腹血糖(FBG)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、内生肌酐清除率(Ccr)、24h尿微量清蛋白(Alb)、尿α1微球蛋白(α1m)及各组动物肾组织中内皮素(ET1),血浆中血栓素B2(TXB2)、6酮前列腺素(6ketoPGF1α)的表达水平。结果12周后,三七总苷治疗组与糖尿病模型组比较,FBG、TC、TG、Ccr、Alb、α1m、肾组织ET1、血浆中TXB2、TXB2/6ketoPGF1α比值均显著下降。结论三七总苷可通过降低糖尿病大鼠早期肾脏高滤过,改善血管内皮功能而起到治疗糖尿病肾病的作用。

Objective To explore the effect of Panax notoginoside(PNS)on the glomerular hyperfiltration and function of vascular endothelium in rats with induced diabetes in its early stage and to probe into the therapeutic action of PNS as well as its underlying mechanisms in the treatment of diabetic nephropathy. Methods A murine type 2 diabetes mellitus model was set up by an intravenous injection of 35 mg·kg -1 of streptozotocin for each Wistar rat after the animal had been fed on high fat forage for 1 month. 50 Wistar rats were randomly divided into 5 equal groups:group N(normal control),group DM(diabetic rats) , group PL (diabetic rats treated with low-dose PNS), group PH(diabetic rats treated with high-dose PNS)and group C( diabetic rats treated with catopril).The following experiment began 2 days after the murine model of diabetes had been set up .Rats of group N and group DM were given disinfected tap water by gastrogavage, q.d., for 12 consecutive weeks. Rats of group PL, group PH and group C were given each by gastrogavage 100 mg·kg -1 of PNS, 200 mg·kg -1 of PNS and 50 mg·kg -1 of catopril in equivalent volumes of solvents,q.d.,for 12 consecutive weeks. Blood, urine and renal tissue samples were then taken for the determination of fasting blood glucose(FBC),serum total cholesterol (TC),serum triglycerides (TG),serum high-density lipoprotein cholesterol(HDL-C),endogenous creatinine clearance rate(CCr),24 h urinary albumin(24 h UAlb),urinary α 1 –microglobulin(Uα 1-m), renal tissue endothelin 1(ET-1),plasma thromboxane B 2 (TXB 2) and plasma 6-keto-prostaglandin F 1α(6-keto-PGF 1α) and plasma nitric oxide(NO). Results At the termination of the 12 week experiment ,the levels of FBG,TC,TG,Ccr, 24 h UAlb, Uα 1-m,ET-1,TX-B 2 and NO, as well as the TXB 2/6-keto-PGF 1α ratio were shown to be significantly lower in rats treated with low-dose or high-dose PNS(rats of group PL and PH)than in rats untreated with PNS(rats of group DM)(P<0.05 or P<0.01)). Conclusion PNS was shown to exert a therapeutic effect on diabetic nephropathy in the rat possibly by alleviating glomerular hyperfiltration and improving vascular endothelial function in the early stage of the disease.