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目的探讨Akt/蛋白激酶B(PKB)信号通路在慢性移植肾肾病(CAN)早期病变中的作用。方法建立Fisher(F344)大鼠到Lewis(LEW)大鼠的左肾移植CAN模型,术后4、8、12及16周时测定24h尿蛋白定量及血肌酐水平,并进行移植肾组织学观察,免疫组化法检测移植肾组织中磷酸化Akt(p-Akt)及基质金属蛋白酶9(MMP-9)的表达,逆转录聚合酶链反应检测肾组织中p-Akt mRNA的表达水平。以单纯切除一侧肾脏的LEW大鼠和F344大鼠为对照。结果移植组术后各检测时间点的24h尿蛋白定量及血肌酐水平呈上升趋势(P<0.05),其组织学改变的Banff评分也呈上升趋势(P<0.05)。移植组各时间点的p-Akt及p-Akt mRNA表达水平均显著高于LEW对照组和F344对照组,且随时间的延长逐步增高(P<0.05);移植组MMP-9表达水平在术后4、8周显著高于LEW对照组和F344对照组(P<0.05),术后16周显著低于LEW对照组和F344对照组(P<0.05)。结论在CAN早期的肾组织中,p-Akt及MMP的表达上调,其表达水平与肾组织的病理改变程度呈正相关,它们可能在CAN早期的发生进展中发挥重要作用。
Objective To investigate the role of Akt / protein kinase B (PKB) signaling pathway in the early stage of chronic allograft nephropathy (CAN). Methods The left renal allograft model from Fisher (F344) rats to Lewis (LEW) rats was established. 24hours, 24th, 12th and 16th week after operation, urinary protein excretion and serum creatinine were measured and histological changes The expressions of p-Akt and MMP-9 in renal allograft tissues were detected by immunohistochemistry. The expression of p-Akt mRNA in renal tissues was detected by reverse transcription-polymerase chain reaction. LEW rats and F344 rats were used as controls to excise only one kidney. Results The urinary protein excretion and serum creatinine in allograft groups were increased (P <0.05), and the histological changes in Banff score were also increased (P <0.05). The levels of p-Akt and p-Akt mRNA in the transplantation group were significantly higher than those in the LEW control group and the F344 control group at each time point, and gradually increased with time (P <0.05). The expression level of MMP-9 in the transplantation group (P <0.05) at 4 weeks and 8 weeks after operation, and significantly lower than LEW control group and F344 control group at 16 weeks after operation (P <0.05). Conclusion The expressions of p-Akt and MMP are up-regulated in renal allografts in early stage of CAN, and the expression of p-Akt and MMP is positively correlated with the pathological changes of renal tissues. They may play an important role in the early development of CAN.