Akt/蛋白激酶B信号传导通路在慢性移植肾肾病早期病变中的作用  

The role of the signaling pathway of Akt/protein kinase B in the early stage of CAN rats

作　　者：李怀富[1] 韩从辉[1] 王玉新[2] 史艳玲[3] 陈玲[3] 周文英[3] 

机构地区：[1]中山大学附属第五医院泌尿外科,珠海519000 [2]厦门市第二医院肾内科 [3]中山大学附属第五医院肾内科,珠海519000

出　　处：《中华器官移植杂志》2007年第5期290-294,共5页Chinese Journal of Organ Transplantation

摘　　要：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 whether the signaling pathway of Akt/protein kinase B （PKB） is involved in the pathogenesis in the early stage of chronic allograft nephropathy （CAN）. Methods The kidneys of Fisher （F344） rats were orthotopically transplanted into Lewis recipients. Animals were harvested respectively at 4th, 8th, 12th and 16th week after transplantation for renal function and histological examination. The expression of p-Akt and MMP-9 was detected by imrnunohistochemical assay,and that expression of p-Akt mRNA by RT-PCR. Results At the 16th week after kidney transplantation, the levels of 24-h proteinuria and serum creatinine in transplant rats were higher significantly than those in LEW controls and F344 controls. The expression of p-Akt protein and rnRNA was up-regulated, and there was a significantly negative correlation between the expression of p-Akt and the quantity of smooth muscular cells （SMCs） in arteriolar wall,the quality of tubulointerstitial infiltrated mononuclear cells and also MMP-9 level. Conclusion The up-regulation of p-Akt played an important role in the pathogenesis such as proliferation and migration of SMCs, infiltrated mononuclear cells in tubulointerstitial in CAN, and may be the signaling pathway leading to the upregulation of MMP-9 expression in the early stage of CAN.

关 键 词：信号传导通路 慢性移植肾肾病 早期病变 AKT 蛋白激酶B 

分 类 号：R692.9[医药卫生—泌尿科学]