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目的探讨加味四君子汤对阿霉素肾病大鼠的治疗作用及对FAK的影响。方法建立阿霉素肾病大鼠模型,以加味四君子汤与强的松对照治疗,7d、21d、35 d测大鼠24 h尿蛋白定性;21 d、35 d取血取肾,检测大鼠血生化指标,观察肾组织病理改变,实时荧光定量PCR检测nephrin、desmin、FAK表达水平的变化,Western blot检测肾组织FAK、蛋白及磷酸化,免疫组化检测nephrin蛋白水平。结果①模型组大鼠出现蛋白尿,足突广泛融合,中药组较模型组改善。②模型组大鼠较正常组nephrin mRNA表达降低,FAK、desmin mRNA表达升高,药物干预后nephrin表达升高,FAK、desmin表达明显降低。③模型组nephrin蛋白表达明显减少,各治疗组较模型组nephrin蛋白水平明显升高。④模型组FAK总蛋白及磷酸化蛋白增高,P<0.01,各治疗组FAK总蛋白及磷酸化蛋白较模型组降低,P<0.05。结论提示肾组织FAK表达增多及其磷酸化可能是产生大量蛋白尿的重要因素,加味四君子汤、泼尼松能抑制FAK活化,有效降低尿蛋白,上调阿霉素肾病大鼠nephrin表达和分布,同时抑制desmin的表达,对受损肾小球足细胞起到一定保护作用。
Objective To investigate the therapeutic effect of Modified Sijunzi Decoction on adriamycin-induced nephropathy in rats and its effect on FAK. Methods The adriamycin-induced nephropathy rat model was established. The rats were treated with Jiawei Sijunzi Decoction and prednisone for 24 hours. The proteinuria of 24-hour urine samples was determined on the 7th day, the 21st day and the 35th day. The changes of nephrin, desmin and FAK were detected by real-time fluorescence quantitative PCR. The protein and phosphorylation of FAK in renal tissue were detected by Western blot. The nephrin protein level was detected by immunohistochemistry. Results ① The proteinuria and foot process of rats in the model group were extensively integrated. The Chinese medicine group improved compared with the model group. ② The expression of nephrin mRNA and the expression of FAK and desmin mRNA in model group were significantly higher than those in normal group. The expression of nephrin and FAK and desmin in model group were significantly lower than those in normal group. ③ The nephrin protein expression in the model group decreased significantly, and the nephrin protein level in each treatment group was significantly higher than that in the model group. (4) FAK total protein and phosphorylated protein in model group increased (P <0.01), FAK total protein and phosphorylated protein in each treatment group decreased compared with model group (P <0.05). The results suggest that increased expression of FAK in kidney and its phosphorylation may be an important factor in producing large amounts of proteinuria. Modified Sijunzi Decoction and prednisone can inhibit the activation of FAK, effectively reduce urinary protein, upregulate nephrin expression and distribution in adriamycin nephropathy rats, While inhibiting the expression of desmin, play a protective role on damaged glomerular podocytes.