康肾方对糖尿病肾病大鼠内皮素的影响

Effects of Kangshen Prescription on Endothelin in Diabetic Nephropathy Rats

目的探讨康肾方对糖尿病肾病(DN)大鼠血浆、肾组织内皮素的影响。方法 SD大鼠单次腹腔注射1%链脲佐菌素(STZ),溶液60 mg.kg-1建立糖尿病模型,成模大鼠随机分为模型组、康肾方高剂量组、康肾方低剂量组及阳性对照组,并设正常组。成模后6周开始上述各药物组大鼠以康肾方、蒙诺灌胃,模型组及正常组以理盐水灌胃,连续8周。观察各组大鼠肾组织电镜病理变化;检测各组大鼠空腹血糖(FBG)、24 h尿白蛋白定量、血脂变化及血浆、肾组织内皮素(ET)水平。结果模型组电镜下可见肾小球毛细血管壁及其内皮细胞基膜增厚,足细胞的足突之间融合形成大的突起,符合DN肾脏纤维化改变;经治疗后各组大鼠肾脏的病理变化均得到改善,尤以高剂量组最为明显。除阳性对照组的FBG、甘油三酯(TG)指标外,各给药组对DN大鼠的FBG、24 h尿白蛋白定量、总胆固醇(TC)、TG、血浆、肾组织ET均有明显的改善(P<0.05,P<0.01);但对高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)的影响不明显(P>0.05)。结论康肾方可改善DN大鼠电镜下肾脏纤维化的病理变化,改善DN的相关指标,其作用机制可能与下调ET水平有关。

Objective To investigate the effects of Kangshen prescription（KP） on endothelin in plasma and kidney tissue of diabetic nephropathy （DN） rats. Methods SD rat models of DN were established by one-dose intraperi- toneal injection of 60 mg·kg^-1 of 1% STZ solution. The model rats were randomly divided into model group, high- dose KP group, low-dose KP group and the positive control group, and normal group was set up. Six weeks after modeling, administration groups were given gavage of KP or monopril respectively, model group and normal group were given garage of saline gavage for 8 continuous weeks. We observed the pathological changes of the renal tissue by electron microscopy, detected the fasting blood glucose（FBG）, 24 h urine protein content, blood lipid and en- dothelin（ET） levels in plasma and renal tissue. Results Pathological changes of DN renal fibrosis were shown in the model group under electron microscopy, such as thickening glomerular capillary wall and its endothelial cell basement membrane, and foot process fusion in podocytes resulting into the formation of large protrusions. After treatment, rat kidney pathological changes were improved in each administration group, especially in the high-dose KP group. Ex- cept FBG and tryglyceride（TG） in the positive control group, FBG, 24 h urine protein content, total cholesterol （TC）, TG and ET in plasma and renal tissue in each administration group were significantly improved （P 〈 0.05 or P 〈 0.01） , but high-density lipoprotein-cholesterol（HDL-C） and low density lipoprotein-cholesterol （LDL-C） remained unchanged（P 〉 0.05）. Conclusion Kangshen prescription can improve the pathological changes of renal fi- brosis under electron microscope in DN rats, and improve the laboratory indicators, and its mechanism may be asso- ciated with the downregulation of ET level.