PI3K/Akt信号通路在慢性肾衰竭大鼠肾组织的表达及肾衰Ⅱ号方的干预作用  

The Expression of PI3K/Akt Pathway in Chronic Renal Failure Rats' Nephridial Tissue and the Effects of “Meliorated Renal Faiure Decotion”

作　　者：杨婧[1] 王琛[1] 祝婷婷[1] 周珊珊[1] 秦军燕[1] 王福岗[1] 何立群[1] 

机构地区：[1]上海中医药大学附属曙光医院肾病科,上海市教委创新团队,肝肾疾病病证教育部重点实验室,(上海中医药大学)上海市中医临床重点实验室(No.14DZ2273200)

出　　处：《中国中西医结合肾病杂志》2015年第9期763-766,I0001,共5页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：国家自然科学基金资助项目(No.30973723);教育部博士学科点专项基金资助项目(No.2012310711004);上海市中医药事业发展三年行动计划项目(No.ZYSNXD-CC-MZY044)

摘　　要：目的:研究肾衰Ⅱ号方对于5/6(ablation/infarction,A/I)肾切除法制备的慢性肾衰竭大鼠肾功能及PI3K/Akt信号通路表达的影响。方法:从SD雄性大鼠中随机抽取14只为假手术组(A组),其余采用5/6(ablation/infarction,A/I)肾切除法制备慢性肾衰竭大鼠模型,随机分为模型组(B组)、西药组(氯沙坦钾+福辛普利)(C组)、中药组(肾衰Ⅱ号方)。给予相应干预,60 d后检测大鼠肾功能[肌酐(Scr)、尿素氮(BUN)]、内生肌酐清除率(Ccr)、血常规(Hb)、左肾重/体重,HE病理染色观察肾组织形态,Western blot法检测组织磷酸化Akt(p-Akt)、总Akt(pan Akt)蛋白表达。结果:(1)造模手术后,与A组比较,各手术组的BUN、Scr明显升高(P<0.01),Ccr明显降低(P<0.01),提示造模成功;(2)与B组比较,C、D组Scr均明显下降(P<0.01,P<0.01)、BUN水平下降(P<0.05,P<0.01),Ccr、Hb均明显升高(P<0.01,P<0.01),左肾重/体重降低(P<0.05);C组与D组比较,在降低Scr和BUN,改善Ccr和Hb,两种药物差异有统计学意义(P<0.05),而在左肾重/体重比值方面两组差别无统计学意义(P>0.05);干预前后比较,C组和D组治疗前后Scr、BUN、Ccr差异有统计学意义(P<0.05),且肾衰Ⅱ号方在降低Scr、BUN,改善Ccr方面优于氯沙坦钾合蒙诺(P<0.05)。(3)肾组织病理显示,两个治疗组病理变化明显减轻,优于模型组。(4)与B组比较,两治疗组皮质、髓质p-Akt/pan Akt比值明显降低(P<0.01,P<0.01);两组间降低p-Akt/pan Akt比值的作用差异有统计学意义(P<0.01),肾衰Ⅱ号方在下调p-Akt/pan Akt比值方面优于氯沙坦钾合蒙诺。结论:肾衰Ⅱ号方可以改善5/6肾切除慢性肾衰竭大鼠的肾脏功能,减轻肾间质纤维化,其作用机制可能是通过下调PI3K/Akt信号通路的表达实现。Objective： To investigate the effects of＂Meliorated Renal Failure Decoction＂on the renal functions and the expression of PI3 K / Akt pathway in the remnant nephridial tissue of 5 /6th kidney ablation / infarction[5 /6A / I]） rats. Methods： SD male rats were made into CRF model by means of 5 /6th kidney ablation / infarction. The study was divided into sham operation group（ Group A）,model group（ Group B） and Cozaar- with- Monopril group（ Group C） and＂MRFD＂group（ Group D）,each with 14 rats. Each group was given relevant intervention treatment once daily by administration for 60 successive days. The serum creatinine（ Scr）,blood urea nitrogen（ BUN）,and creatinine clearance rate（ CCr） were detected. The pathomorphology of the nephridial tissue was observed. The expressions of p- Akt、pan Akt protein in the remnant renal cortex and medulla were assessed by Western blotting analysis. Results：（ 1） After being modeled,compared with the sham operation group,the levels of SCr and BUN increased（ P〈0. 01） and the level of CCr decreased（ P〈0. 01） in the operation groups,indicating successful modeling.（ 2） After intervention treatment,in Group C and D compared with Group B,the level of Scr、BUN decreased（ P〈0. 01,P〈0. 01）,BUN decreased（ P〈0. 05,P〈0. 01）,Ccr、Hb value increased（ P〈0. 01,P〈0. 01）,and the ratio of left renal weight to body weight came down（ P〈0. 05）. Between Group C and Group D,differences were found existing in the value of Scr、BUN、Ccr、Hb value（ P〈0. 05）. Comparing the Pre- and- After results of the intervention treatment,differences between Group C and Group D were significant in treating Scr、BUN and Ccr（ P〈0. 05）. ＂MRFD＂had better effect in decreasing Scr、BUN and improving Ccr than Cozaar- with- Monopril（ P〈0. 05） but not in improving the ratio of left renal weight to body weight（ P〉0. 05）.（ 3） The pathology of the nephridial tissue showed that the pathological changes in gr

关 键 词：肾衰Ⅱ号方 肾纤维化 PI3K/AKT 信号通路 

分 类 号：R692.5[医药卫生—泌尿科学]