水陆地黄胶囊对糖尿病肾病大鼠的药效学及作用机制研究

Preliminary pharmacodynamics research of Shuiludihuang Capsule on rats with type 2 diabetic nephropathy

目的考察水陆地黄胶囊对高脂高糖饮食联合小剂量链脲佐菌素(STZ)致糖尿病肾病大鼠的药效学指标的影响,并初步探讨其机制。方法通过高脂高糖饮食联合小剂量STZ进行2型糖尿病肾病动物造模。通过测定空腹血糖(FBG)、总胆固醇(TC)、三酰甘油(TG)、尿微量白蛋白(UMA)、肾质量、肾脏指数等指标观察其药效,考察其对肾脏病理改变的影响。通过免疫组化法测定肾脏组织Angptl4、Desmin及NF-κB表达,Western blotting法检测肾组织Angptl4、Desmin表达水平;ELISA法测定血清脂联素(APN)、瘦素(LEP)的水平及尿Angptl4水平。结果与模型组比较,水陆地黄胶囊(9、6 g/kg)各组大鼠肾质量、肾脏指数、血糖、LEP及肾脏组织Angptl4、Desmin及NF-κB表达明显降低,体质量、血清APN水平明显升高,具有统计学意义(P<0.05、0.01)。结论水陆地黄胶囊可以调节糖尿病肾病大鼠的糖脂代谢,减轻炎症反应,降低肾组织Angptl4、Desmin及NF-κB蛋白表达水平,改善肾足细胞损伤,降低尿蛋白,达到延缓肾脏纤维化、硬化作用。其作用机制可能与Angptl4、Desmin及NF-κB等通路有关。

Objective To study the preliminary pharmacodynamics effect of Shuiludihuang Capsule on rats with type 2 diabetic nephopathy induced by high-fat and sugar diet combined low dose streptozotocin (STZ), and to investigate its mechanism. Methods Type 2 diabetic nephropathy animal model was established by feeding with high fat and sugar diet combined with low dose of STZ. The FBS, TC, TG, UMA, kidney weight, the hypertrophy index, etc were measured to study its effects of reducing blood glucose and protecting kidney, and its pharmacodynamic effects were expounded by kidney pathological section. The expressions of Angptl4, Desmin and NF-κB in kidney tissues were tested by immunohistochemistry, The expressions of Angptl4 and Desmin in kidney tissues were tested by western blotting, and APN, LEP and Urine Angptl4 were tested by ELISA to probe into its mechanism tentatively. Results Compared with the model control group, kidney weight, the hypertrophy index, FBG, TC, TG, LEP and the expressions of Angptl4, Desmin and NF-κB in rats of each group (9, 6 mg/kg) were significantly decreased, and body mass, the serum APN level were significantly increased, with significant difference (P < 0.05, P < 0.01). Conclusion Shuiludihuang capsule can regulate glucose and fat metabolism, reduce inflammation, reduce Angptl4, Desmin and NF-κB expression levels in renal tissue, improve renal podocyte injury, reduce urinary protein, and delay renal fibrosis and sclerosis. Its mechanism may be related to Angptl4, Desmin and NF-κB pathways.