MG-132对慢性肾衰大鼠治疗作用的初步研究

Therapeutic effect of MG-132 on chronic renal failure rats

目的探讨蛋白酶体抑制剂在慢性肾衰竭大鼠中的治疗作用。方法采用部分肾动脉结扎加肾切除法复制慢性肾衰竭大鼠模型,RT-PCR法测定主动脉泛素、泛素结合酶mRNA的表达变化,光镜观察肾脏病理改变,酶法测定血肌酐、尿素氮及血脂变化。结果与对照组比较,单纯手术组大鼠肾小球明显硬化、间质纤维化、炎细胞浸润,血肌酐、尿素氮水平均显著升高,主动脉泛素Ub及泛素连接酶E2 mRNA表达水平也显著增加。蛋白酶体抑制剂MG-132治疗4-6个月后大鼠主动脉泛素Ub及泛素连接酶E2 mRNA表达显著降低,同时,病理检查显示肾脏间质纤维化和炎症浸润明显减轻,血肌酐、尿素氮升高水平也显著低于单纯手术组。结论泛素蛋白酶体信号通路活化在慢性肾功能衰竭病理进程中发挥了重要作用。

Objective To investigate the therapeutic action of MG-132 on the chronic renal failure rats. Methods The chronic renal failure（CRF） rats model was established by right nephrectomy and left branch renal artery ligation. The mRNA expression of ubiquitin and ubiquitin-conjugating enzymes（E2） was analyzed by RT-PCR. And the renal function was analyzed by enzymic method. Results Compared with the control group, there were obvious mesangial hyperplasia and renal glomeruler sclerosis and interstitial fibrosis and imflammatory cells infiltration, the concentration of blood creatinine and urea was elevated markedly, the mRNA expression of Ub, E2 in uremic rats＇ aorta was also evidently higher in the CRF model rats. But compared with the simple model rats, the above-mentioned renal pathological alteration and renal function were amelimorated by the proteasome inhibitor MG-132 treatment, and the mRNA expression of Ub, E2 in uremic rats＇ aorta was also inhibited. Conclusion The ubiquitin-proteasome pathway plays an important role in the pathogenesis of chronic renal failure.