黄芪菟箭合剂对糖尿病大鼠肾脏足细胞保护作用机制的研究

Protective Effects of Huangqitujian Decoction on Podocytes in Diabetic Rats

目的观察中药黄芪菟箭合剂对糖尿病大鼠尿白蛋白排泄率及其对肾足细胞保护及凋亡相关指标的影响。方法链脲佐菌素(STZ)诱导成模的糖尿病大鼠随机分为糖尿病组(DM组)、黄芪菟箭合剂治疗组(CM组)、缬沙坦组(V组);另设正常对照组(CON组)。CM组以10g/(kg·d)灌胃黄芪菟箭合剂、V组以40mg/(kg·d)灌胃缬沙坦。干预12周后,分别检测大鼠的肾/体重比、尿白蛋白肌酐比(ACR)、肌酐清除率(CCR),并以Western blot法检测肾皮质ZO-1、nephrin、caspase-3及NF-κB的蛋白表达。结果DM组的肾/体重比、ACR、CCR均显著高于CON组(P<0.05);CM组和V组的肾/体重比、ACR、CCR较DM组均明显下降(P<0.05),CM组和V组之间比较,差异无统计学意义(P>0.05)。与CON组比较,DM组的肾皮质ZO-1、nephrin的蛋白表达显著降低(P<0.01),而caspase-3和NF-κB蛋白表达则显著升高(P<0.01)。与DM组比较,CM组及V组的肾皮质ZO-1和nephrin表达量升高,caspase-3及NF-κB表达量降低,差异有统计学意义(P<0.05)。结论黄芪菟箭合剂可抑制糖尿病大鼠肾脏高滤过状态、降低尿白蛋白排泄率,其肾保护机制可能与其保护足细胞、抑制足细胞凋亡有关。

Objective To investigate Huangqitujian decoction′s effects on urinary albumin excretion and its effects on renal expression of zonulaaoccludens protein-1(ZO-1),nephrin,caspase-3 and NF-κB in streptozocin(STZ)induced diabetic rats.Methods STZ induced diabetic rats were divided into diabetic control group(DM),Huangqitujian decoction treatment group(CM),Valsartan treatment group(V),and the normal rats were set as normal control group(CON).In CM group,rats were fed with 10g/(kg·d)of Huangqitujian decoction;in V group,valsartan was given orally at the dose of 40mg/(kg·d).After 12 weeks intervention,kidney/body weight ratio(KWR),urinary albumin to creatinine ratio(ACR)and creatinine clearance rate(CCR)were detected.The protein expression of ZO-1,nephrin,caspase-3 and NF-κB in renal cortex were assessed by Western blot.Results In DM group,KWR,ACR and CCR increased than in NC group(P<0.05).KWR,ACR and CCR showed decreased in both V group and CM group,than in DM group(P<0.05);there were no significant differences between V group and CM group(P>0.05).Compared with CON group,decreased expression of ZO-1 and nephrin and elevated expression of caspase-3 and NF-κB were shown in DM group(P<0.01).Compared with DM group,both of V group and CM group showed elevated expression of ZO-1 and nephrin,and decreased expression of caspase-3 and NF-κB(P<0.05).Conclusion Huangqitujian decoction can inhibit renal hyperfiltration and reduce the excretion of urinary albumin in diabetic rats.Its renal protective effects might be related to the protection of podocytes and the inhibition of podocyte apoptosis.