PI3K抑制剂LY294002对急性肾损伤大鼠肾功能及细胞自噬的影响  

Effects of PI3K inhibitor LY294002 on renal function and autophagy in rats with acute kidney injury

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作  者:龙成美[1] 傅俊 杨锦然 LONG Chengmei;FU Jun;YANG Jinran(Department of Organ Transplantation,Jiangxi Provincial People's Hospital,the First Affiliated Hospital of Nanchang Medical College,Jiangxi Province,Nanchang 330006,China)

机构地区:[1]江西省人民医院南昌医学院第一附属医院器官移植科,江西南昌330006

出  处:《中国当代医药》2024年第3期7-12,共6页China Modern Medicine

基  金:江西省卫生健康委科技计划项目(202130044)。

摘  要:目的探究LY294002对急性肾损伤(AKI)大鼠肾功能及细胞自噬的影响。方法将36只SD大鼠采用随机单位组设计分组法分为对照(control)组、假手术(sham)组、模型(model)组、LY294002预处理(I/R+LY294002)组,每组9只。LY294002预处理组连续腹腔注射LY294002(40μl/d),模型组腹腔注射等量无菌生理盐水,干预时间为14 d。14 d后除对照组外,其余大鼠均行手术,假手术组仅暴露双侧肾脏及肾蒂,模型组及LY294002预处理组进一步建立大鼠肾缺血再灌注损伤(RIRI)模型(缺血45 min,再灌注24 h)模拟AKI。建模成功后收集各组血液和肾脏,检测血清中肾损伤相关指标,观察肾脏组织病理改变,检测PI3K/AKT信号通路和自噬相关蛋白的表达情况。结果模型组血清肌酐(SCr)、尿素氮(BUN)及肾损伤分子1(Kim-1)的浓度高于对照组及假手术组,差异有统计学意义(P<0.05)。LY294002预处理组SCr、BUN及Kim-1的浓度低于模型组,差异有统计学意义(P<0.05)。LY294002预处理组可观察到RIRI大鼠肾脏组织病理改变如肾小管梗阻扩张、血管扩张充血、间质水肿得到减轻。模型组p-AKT/AKT和p-PI3K/PI3K的相对表达量和LC3Ⅱ、Beclin-1的表达高于对照组、假手术组,差异有统计学意义(P<0.05)。LY294002预处理组p-AKT/AKT和p-PI3K/PI3K的相对表达量和LC3Ⅱ、Beclin-1的表达低于模型组,差异有统计学意义(P<0.05)。结论LY294002通过抑制PI3K/AKT信号通路,抑制了细胞自噬,肾脏损伤得到改善。这将为防治AKI提供一个新的思路。Objective To explore the effect of LY294002 on renal function and autophagy in rats with acute kidney injury(AKI).Methods Thirty-six SD rats were divided into control group,sham group,model group and LY294002 preconditioning(I/R+LY294002)group,using the randomized unit group design,with nine rats in each group.LY294002 was injected continuously intraperitoneally(40μl/d)in the LY294002 preconditioning group,and an equal amount of sterile saline was injected intraperitoneally in the model group,and the intervention time was 14 days.After 14 days,all rats except the control group underwent operation.Only bilateral kidneys and renal hila were exposed in the sham group,while the rat renal ischemia-reperfusion injury(RIRI)model(ischemia for 45 min,reperfusion for 24 h)was further established to simulate AKI in the model group and the LY294002 preconditioning group.After successful modeling,blood and kidneys were collected from each group,the renal injury-related indexes in serum were detected,histopathological changes in kidneys were observed,the expression of PI3K/AKT signaling pathway and autophagy-related proteins were detected.Results The concentrations of serum creatinine(SCr),blood urea nitrogen(BUN)and kidney injury molecule 1(Kim-1)in the model group were higher than those in the control group and sham group,and the differences were statistically significant(P<0.05).The concentrations of SCr,BUN and Kim-1 in the LY294002 preconditioning group were lower than those in the model group,and the differences were statistically significant(P<0.05).Histopathological changes in the kidneys of RIRI rats,such as dilatation of tubular obstruction,vasodilatation and congestion,and interstitial oedem were observed to be attenuated in the LY294002 preconditioning group.The relative expression of p-AKT/AKT and p-PI3K/PI3K and the expression of LC3Ⅱand Beclin-1 in the model group were higher than those in the control group and sham group,and the differences were statistically significant(P<0.05).The relative expression of p-

关 键 词:LY294002 急性肾损伤 PI3K/AKT信号通路 自噬 肾缺血再灌注损伤 

分 类 号:R692[医药卫生—泌尿科学]

 

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