中介素对造影剂急性肾损伤及管周毛细血管损伤的保护作用及其机制  

Protective effect of Intermedin on contrast-induced acute kidney injury and peritubular capillary injury and its mechanism

作　　者：张博劲 顾瑞远 张瑞婧[3] 董红霖[2] 郑国平 Zhang Bojin;Gu Ruiyuan;Zhang Ruijing;Dong Honglin;Zheng Guoping(Department of Biochemistry and Molecular Biology,School of Basic Medicine,Shanxi Medical University,Taiyuan 030001,China;Department of Vascular Surgery,the Second Hospital of Shanxi Medical University,Taiyuan 030001,China;Department of Nephrology,the Second Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学基础医学院生物化学与分子生物学教研室,太原030001 [2]山西医科大学第二医院血管外科,太原030001 [3]山西医科大学第二医院肾内科,太原030001

出　　处：《中华实验外科杂志》2022年第9期1705-1708,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金(81770695)。

摘　　要：目的探究中介素(IMD)是否通过磷酸肌醇3激酶(PI3K)/蛋白激酶B(Akt)通路保护造影剂急性肾损伤(CIAKI)及管周毛细血管(PTC)损伤。方法24只雄性SD大鼠,按随机数字表法分为对照组(N组),模型组(CM组),模型+IMD组(IMD组)和模型+IMD+LY294002组(LY组),每组6只。CM组大鼠给予碘海醇(15 ml/kg)并建立CIAKI模型,N组给予等量生理盐水。IMD组在建模前24 h给予IMD[300 ng/(kg·h)],LY组在建模30 min前给予PI3K抑制剂LY294002(0.3 mg/kg)。建模后24 h,酶联免疫吸附试验(ELISA)检测血清肌酐(Scr)水平,苏木精-伊红(HE)染色观察肾小管,蛋白质印迹法(Western blot)和免疫组织化学检测相关蛋白表达,电子显微镜观察PTC内皮细胞。组间比较采用t检验和单因素方差分析。结果各组Scr水平显示,CM组[(59.325±7.856)μmol/L]高于N组[(30.930±6.595)μmol/L],IMD组[(39.230±6.759)μmol/L]低于CM组,LY组[(53.985±2.966)μmol/L]高于IMD组,差异有统计学意义(tScr=7.874、7.007、3.759,P<0.05);各组CD34阳性面积百分比,磷酸化蛋白激酶B(p-Akt),血管内皮生长因子(VEGF),血管内皮细胞钙黏连蛋白(VE-cadherin)表达均显示,CM组[(5.732±0.452)%,1.000±0.000,1.000±0.000,1.000±0.000]低于N组[(7.605±1.053)%,1.373±0.210,1.530±0.228,1.511±0.264],IMD组[(7.888±0.886)%,1.748±0.334,1.329±0.111,1.267±0.117]高于CM组,LY组[(5.789±0.537)%,0.781±0.078,0.905±0.043,0.945±0.040]低于IMD组,差异有统计学意义(t_(CD34)=6.935、9.198、8.596,t_(p-Akt)=4.450、5.495、6.915,t_(VEGF)=5.704、7.276、8.741,t_(VE-cadherin)=4.742、5.601、6.398,P<0.05);各组肾小管及PTC内皮细胞均显示N组正常,CM组损伤,IMD组较CM组损伤减轻,LY组较IMD组损伤加重。结论IMD能够通过PI3K/Akt通路保护CIAKI及PTC损伤。Objective To explore whether Intermedin(IMD)protects contrast-induced acute kidney injury(CIAKI)and peritubular capillary(PTC)injury through the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)pathway.Methods A total of 24 male SD rats were divided into control group(group N),model group(group CM),model+IMD group(group IMD)and model+IMD+LY294002 group(group LY)according to the random number table method.Rats in group CM were injected with iohexol(15 ml/kg)to establish the CIAKI model.Group N was injected with an equal volume of normal saline,the group IMD was injected with IMD[(300 ng/(kg·h)]24 h before modeling,and the group LY was injected with the PI3K inhibitor LY294002(0.3 mg/kg)30 min before modeling.At 24 h after modeling,the serum creatinine(Scr)level was detected by enzyme-linked immunosorbent assay(ELISA),the renal tubules were observed by hematoxylin-eosin(HE)staining,the expression of related proteins was detected by Western blotting and immunohistochemistry,and the PTC endothelial cells were observed by electron microscopy.Comparisons between groups was done by t-test and one-way ANOVA.Results The Scr level in group CM[(59.325±7.856)μmol/L]was higher than in group N[(30.930±6.595)μmol/L],that in group IMD[(39.230±6.759)μmol/L]was lower than in group CM,and that in group LY[(53.985±2.966)μmol/L]was higher than in IMD group,and the difference was statistically significant(tScr=7.874,7.007,3.759,P<0.05).Percentage of CD34 positive area,expression of phosphorylated protein kinase B(p-Akt),vascular endothelial growth factor(VEGF)and VE-cadherin in group CM[(5.732±0.452)%,1.000±0.000,1.000±0.000,1.000±0.000)]were lower than in group N[(7.605±1.053)%,1.373±0.210,1.530±0.228,1.511±0.264],those in group IMD[(7.888±0.886)%,1.748±0.334,1.329±0.111,1.267±0.117]were higher than in group CM,and those in group LY[(5.789±0.537)%,0.781±0.078,0.905±0.043,0.945±0.040]was lower than in IMD group,and the difference was statistically significant(t_(CD34)=6.935,9.198,8.596;t_(p-Akt)=4.450,5.49

关 键 词：急性肾损伤 中介素 管周毛细血管 内皮损伤 

分 类 号：R692[医药卫生—泌尿科学]