米力农注射液对肾缺血再灌注损伤大鼠PDE3/cAMP/PKA信号通路及肾功能的影响  

Effects of Milrinone Injection on PDE3/cAMP/PKA Signal Pathway and Renal Function in Rats with Renal Ischemia-reperfusion Injury

作　　者：邵欢[1] 祝莹 曹洪富[1] 王丽萍[1] SHAO Huan;ZHU Ying;CAO Hongfu(Department of Pharmacy,Wuxi Second People’s Hospital,Wuxi(214002))

机构地区：[1]江苏省无锡市第二人民医院药剂科,无锡214002 [2]南京医科大学药学院,无锡214000

出　　处：《中国中西医结合肾病杂志》2021年第4期292-295,共4页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：苏州市“科教兴卫”青年科技项目(No.KJXW20140480)。

摘　　要：目的:探究米力农注射液对肾缺血再灌注损伤(IRI)大鼠磷酸二酯酶3(PDE3)/环腺苷酸(cAMP)/蛋白激酶A(PKA)信号通路及肾功能的影响。方法:SD大鼠随机分为假手术组、模型组、地塞米松(5 mg/kg)组、米力农低(125μg/kg)、中(250μg/kg)、高(500μg/kg)剂量组,每组12只,除假手术组外,其余各组建立IRI大鼠模型,分组处理后,检测大鼠肾功能指标血尿素氮(BUN)、血清肌酐(Scr)水平;以苏木精-伊红染色(HE)检测大鼠肾组织病理形态;以试剂盒检测大鼠肾组织SOD、MDA及cAMP水平;以酶联免疫吸附法(ELISA)检测血清TNF-α,IL-6;以蛋白免疫印迹法检测肾组织PDE3、PKA蛋白表达。结果:与假手术组相比,模型组大鼠肾组织球囊黏连,肾小管结构水肿膨胀,肾上皮细胞变性、坏死,形成空泡,显示严重的病理损伤,Scr、BUN、血清TNF-α、IL-6水平、肾组织MDA水平及PDE3蛋白表达升高(P<0.05),肾组织cAMP、SOD水平及PKA蛋白表达明显降低(P<0.05)。与模型组相比,米力农低、中、高剂量组及地塞米松组大鼠肾组织病理损伤减轻,Scr、BUN、血清TNF-α、IL-6水平、肾组织MDA水平及PDE3蛋白表达降低(P<0.05),cAMP、SOD水平及PKA蛋白表达升高,且米力农各组呈剂量依赖性(P<0.05)。结论:米力农注射液可下调PKA表达激活cAMP/PKA信号,从而抑制炎症反应,降低氧化应激,加快肾组织缺血再灌注损伤的修复。Objective:To investigate the effects of milrinone injection on phosphodiesterase 3(PDE3)/cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)signaling pathway and renal function in rats with renal ischemia-reperfusion injury.Methods:SD rats were randomly divided into sham operation group,model group,dexamethasone(5 mg/kg),low(125μg/kg),medium(250μg/kg),high(500μg/kg)dose milrinone groups,with 12 in each group,except for the sham operation group,the other groups established the rat model of renal ischemia-reperfusion injury,after treatment,the levels of blood urea nitrogen(BUN)and serum creatinine(Scr)were measured;hematoxylin eosin staining(HE)was used to detect the renal pathological morphology of rats;the levels of SOD,MDA and cAMP in renal tissue of rats were detected by kit;the serum TNF-αand IL-6 were detected by enzyme-linked immunosorbent assay(ELISA);and the expressions of PDE3 and PKA in renal tissue were detected by Western blot.Results:Compared with the sham operation group,the glomerular adhesion,edema and swelling of renal tubular structure,degeneration and necrosis of renal epithelial cells,vacuole formation,and severe pathological damage were observed in rats in the model group,the Scr,BUN,levels of TNF-αand IL-6 in serum,level of MDA in renal tissue and expression of PDE3 protein were significantly higher(P<0.05),and the levels of cAMP and SOD in renal tissue and expression of PKA protein were significantly lower(P<0.05).Compared with the model group,the pathological damage of renal tissue in the low,medium and high dose milrinone groups and dexamethasone group was alleviated,the Scr,BUN,levels of TNF-αand IL-6 in serum,level of MDA in renal tissue and expression of PDE3 protein were significantly lower(P<0.05),the levels of cAMP and SOD in renal tissue and expression of PKA protein were significantly higher(P<0.05).Conclusion:Milrinone injection can down-regulate PKA expression,activate cAMP/PKA signal,inhibit inflammatory response,reduce oxidative stress level and alleviate renal isc

关 键 词：米力农注射液 肾缺血再灌注损伤 磷酸二酯酶3/环腺苷酸/蛋白激酶A信号信号 肾功能 

分 类 号：R692[医药卫生—泌尿科学]