菟箭合剂对糖尿病大鼠肾组织蛋白激酶C活性作用的研究

目的 :观察菟箭合剂对实验性糖尿病肾病大鼠肾组织蛋白激酶C(PKC)活性、肾功能及肾脏结构的影响。方法 :单肾切除加链脲佐菌素 (STZ)腹腔注射制作糖尿病肾病动物模型。中药菟箭合剂 (20g·kg^-1·d^-1)和阳性对照药缬沙坦 (2 0mg·kg^-1·d^-1)干预治疗 12周 ,用氚标记的二丁酸佛波醇酯 ([³H]PDBu)结合法测定大鼠肾组织PKC活性 ,检测 24 h尿蛋白排出量 (Upro) ,肾脏常规染色光镜观察病理变化。结果 :12周时单肾糖尿病大鼠肾组织出现肾小球硬化病理改变 ,Upro明显升高 ,细胞膜PKC活性 (mPKC)明显升高 ,细胞浆PKC活性 (cPKC)明显降低 ,mPKC和cPKC比值 (M/C)明显升高。菟箭合剂和缬沙坦干预治疗显著降低Upro ,降低mPKC和M/C ,升高cPKC(P<0.01) ,改善肾组织病理改变。结论 :菟箭合剂对单肾切除STZ糖尿病大鼠具有肾保护作用 ,推测部分地通过抑制肾组织PKC激活途径来达到的。

Effect of Tujian decoction on protein kinase C activity in renal cortex in diabetic rat

Objective: To investigate influence of administration of Tujian decoction (Chinese herbal medicine) on protein kinase C (PKC) activity,renal function and structure in diabetic rat kidney. Method: Experimental diabetic nephropathy model was induced by nephrectomy combined with streptozotocin (STZ) injection in sprague-dawley rat. Tujian decoction (20 g·kg ^-1·d ^-1) and Valsartan(20 mg·kg^-1·d^-1)were orally administrated respectively for 12 weeks. PKC activity was measured by [³H]phorbol 12,13-dibutyrate ([³H]PDBu) binding assay. 24h urine protein excretion (Upro) and renal pathological changes were observed. Result: In 12th week, diabetic nephrectomized rats developed proteinuria, glomerulosclerosis, increased membrane PKC activity (mPKC), decreased cytosol PKC (cPKC), and increased ratio of mPKC and cPKC (M/C). Administration of Tujian decoction or Valsartan led to a reduction in proteinuria, structural injury, mPKC and M/C, and a recovery in cPKC. Conclusion: Tujian decoction possesses a renoprotective effect on diabetic nephrectomized rat, at least partially via the inhibition of PKC activation in renal cortex.