栝楼瞿麦汤对糖尿病肾病大鼠脂肪因子和足细胞nephrin的影响

目的:观察栝楼瞿麦汤(GLQM)对糖尿病肾病(DN)大鼠血清血脂,脂肪因子和足细胞nephrin的影响,探讨其可能的作用机制。方法:对SD大鼠采用高糖高脂饮食、单侧肾切除及腹腔注射链脲佐菌素(STZ)的方法制备DN模型。造模成功后,随机分为模型组,GLQM低(GLQM-L),中(GLQM-M),高(GLQM-H)剂量组和缬沙坦组,另设空白组。治疗组从实验开始第4周起,GLQM低、中、高剂量组分别以1.4,2.8,5.6 g·kg-1灌胃(ig),缬沙坦组4.8×10-3g·kg-1ig,空白组及模型组均予2.8 g·kg-1蒸馏水ig,1次/d,连续12周。观察大鼠一般状况;全自动生化分析仪检测血清三酰甘油(TG),胆固醇(CHO),高密度脂蛋白(HDL)和低密度脂蛋白(LDL)水平;酶联免疫吸附法(ELISA)检测血清脂联素(APN),瘦素(LEP)的水平;光镜下观察肾组织病理变化;电镜下观察足细胞形态变化;蛋白免疫印迹法(Western blot)法检测肾组织nephrin蛋白表达情况。结果:与模型组比较,GLQM低、中、高剂量组的TG,CHO,LDL明显降低(P0.05,P0.01),HDL明显升高(P0.05),GLQM中、高剂量组和缬沙坦组的LEP明显降低(P0.01),APN明显升高(P0.01)。病理学检查显示,各治疗组肾组织和足细胞的病理改变较模型组均有所减轻。经栝楼瞿麦汤干预后,各中药治疗组及缬沙坦组nephrin蛋白表达水平有所上调(P0.05)。结论:栝楼瞿麦汤可以通过改善脂代谢、干预脂肪因子以及维持nephrin的表达,减轻肾组织及足细胞的损伤,从而延缓DN病情发展。

Effect of Gualou Qumai Tang on Adipokines and Nephrin of Podocyte in Rats with Diabetic Nephropathy

Objective: To observe the effects of Gualou Qumai Tang (GLQM) on serum lipids, adipokines and nephrin of podocyte in rats with diabetic nephropathy (DN) and discuss possible mechanism. Method: DN model was established by SD rats with high glucose and fat diet, unilateral nephrectomy and intraperitoneal injection of streptozotocin (STZ). After successful modeling, the rats were randomly divided into DN model group, low dose GLQM (GLQM-L), medium dose GLQM (GLQM-M), and high dose GLQM (GLQM-H) groups, valsartan group, and additionally a blank control group was set. The rats in GLQM low, medium and high dose groups received ig administration of 1.4, 2.8 and 5.6 g·kg^-1 GLQM respectively from 4^th week; the rats in valsartan group received ig administration of 4.8×10^-3 g·kg^-1, and the rats in control and model group were given with 2.8 g·kg^-1 distilled water, once a day for 12 weeks. Then the general status of the rats was observed; serum levels of triglyceride (TG), cholesterol (CHO), high density lipoprotein (HDL) and low density lipoprotein (LDL) were detected by automatic biochemical analyzer; serum levels of adiponectin (APN) and leptin (LEP) were detected by using enzyme-linked immunosorbent assay (ELISA). Then pathological changes of renal tissues were observed under light microscope, morphological changes of podocyte under electron microscope and nephrin expression in renal tissues was detected by using Western blot method. Result: As compared with the model group, the TG, CHO and LDL levels were significantly decreased in low, medium and high dose GLQM groups (P<0.05, P<0.01), and HDL was increased significantly (P<0.05). The LEP level was significantly decreased in medium and high dose GLQM groups and valsartan group (P<0.01); APN was increased significantly (P<0.01). Pathological examination showed that the pathological changes of renal tissues and podocytes in the treatment groups were less than those in the model group. After the intervention of GLQM, the protein expression levels of nephrin were increased in Chinese medicine groups and valsartan group (P<0.05). Conclusion: GLQM can reduce renal tissue and podocyte damages and delay the development of DN by improving blood-lipid metabolism, interfering adipokine and maintaining the expressions of nephrin.