AMPK信号通路在小鼠急性肾损伤发生中的作用

Role and Mechanism of AMPK Signaling Pathway in the Development of Acute Kidney Injury in Mice

目的探讨磷酸腺苷激活蛋白酶(adenosine phosphate activating protease,AMPK)信号通路在小鼠急性肾损伤发生中的作用。方法SPF级BALB/c雄性小鼠(48只)随机分为两组,对照组与实验组各24只。实验组采用阿德福韦酯40 mg/kg灌胃处理,1次/周,持续2次;对照组用等量等渗盐水进行灌胃处理。采用全自动生化分析仪测定血清尿素氮(BUN)与肌酐(SCr)含量,采用Western blotting检测肾组织中AMPK、Keap-1的表达,同时进行组织病理学评分。结果处理2周、4周、6周后,实验组的血清BUN与SCr水平都显著高于对照组(P<0.05);实验组的肾脏组织病理学评分都显著高于对照组(P<0.05);实验组的肾脏AMPK与Keap-1蛋白相对表达水平都显著高于对照组(P<0.05)。结论小鼠急性肾损伤可激活AMPK信号通路,诱导AMPK与Keap-1表达量上升,导致肾脏组织损伤与肾功能下降。

Objective To investigate the role and mechanism of Adenosine phosphate activating protease(AMPK)signaling pathway in the development of acute kidney injury in mice.Method 48 SPF BALB/C male mice were randomly divided into two groups:control group(n=24)and experimental group(n=24).The experimental group were treated with adefovir dipivoxil 40 mg/kg,once a week for 2 times,while the control group were treated with equal amount of isotonic saline.Serum urea nitrogen(BUN)and creatinine(SCr)were measured by automatic biochemical analyzer.The expression of AMPK and Keap-1 in renal tissue were detected by Western blotting,and histopathological scores were also obtained.Results After 2 weeks,4 weeks,and 6 weeks of treatment,serum BUN and SCr values in the experimental group were significantly higher than those in the control group(P<0.05),the histopathological scores of the kidneys in the experimental group were significantly higher than those in the control group(P<0.05),and the relative expression levels of AMPK and Keap-1 protein in the kidneys of the experimental group were significantly higher than those in the control group(P<0.05).Conclusion Acute kidney injury in mice can activate the AMPK signaling pathway and induce the expression of AMPK and Keap-1 increase,which leads to the deterioration of renal tissue and renal function.