尿毒症患者血清PTH对大鼠肾小球系膜细胞体外增殖及PI3KAktmTOR信号通路的影响  

Effect of serum PTH of uremic patients on proliferation and PI3K/Akt/mTOR signaling pathway of rat mesangial cells in vitro

作　　者：陈霓 刘秋洪[2] 吴丹 CHEN Ni;LIU Qiuhong;WU Dan(Department of Urology, The Third People's Hospital of Chengdu, Chengdu 610031, China;Department of Geriatric, Sichuan Revolutionary Disabled Military Hospital, Chengdu 610502, China)

机构地区：[1]成都市第三人民医院肾内科,四川成都610031 [2]四川省革命伤残军人医院老年病科,四川成都610502

出　　处：《西部医学》2021年第6期804-808,共5页Medical Journal of West China

基　　金：四川省科技厅医药卫生专项课题(GH20187576087)。

摘　　要：目的探讨尿毒症患者血清甲状旁腺激素(PTH)对大鼠肾小球系膜细胞(GMC)体外增殖及磷脂酰肌醇-3/蛋白激酶/哺乳动物雷帕霉素靶蛋白(PI3K/Akt/mTOR)信号通路的影响。方法选取2015年1月~2018年9月成都市第三人民医院肾内科收治的72例尿毒症患者,根据血清PTH水平分为正常组16例、轻中度增高组33例、重度增高组23例,常规体外培养大鼠GMC细胞,比较3组12、24、48 h GMC细胞光密度值、GMC细胞周期时相分布、mTOR、Caspase-3表达情况。结果重度增高组12、24、48 h GMC细胞光密度值均高于正常组、轻中度增高组,且轻中度增高组12、24、48 h GMC细胞光密度值均高于正常组(P<0.05);3组GMC细胞光密度值在12、24、48 h随时间推移逐渐递增(P<0.05);与正常组相比,轻中度增高组、重度增高组GMC细胞进入S、G2/M期明显增多(P<0.05);重度增高组GMC细胞进入S、G2/M期细胞多于轻中度增高组(P<0.05);轻中度增高组、重度增高组mTOR表达量高于正常组,Caspase-3表达量低于正常组(P<0.05);重度增高组mTOR表达量高于轻中度增高组,Caspase-3表达量低于轻中度增高组(P<0.05)。结论尿毒症患者血清可导致GMC增殖,且甲状旁腺功能亢进可促进GMC增殖,提高PI3K/Akt/mTOR信号通路表达,PI3K/Akt/mTOR信号通路抑制剂可能有助于抑制GMC增殖,延缓尿毒症患者肾功能衰竭进程。Objective To explore the effect of serum parathyroid hormone(PTH)on the proliferation of rat glomerular mesangial cells(GMC),the impact of the pathway and the phosphatidylinositol-3/protein kinase/mammalian rapamycin target protein(PI3K/Akt/mTOR)signal in uremic patients.Methods 72 uremic patients admitted to the Department of Nephrology of the third people's Hospital of Chengdu from January 2015 to September 2018 were selected and divided into normal group(n=16,PTH 1-10 pmol/L),mild to moderate increase group(n=33,PTH 11-30 pmol/L)and severe increase group(n=23,PTH>30 pmol/L)according to serum PTH level.GMC cells were cultured in vitro.The optical density,cell cycle distribution,mTOR and Caspase 3 expression of GMC cells at 12 h,24 h and 48 h were compared among the three groups.Results The optical density of GMC cells at 12 h,24 h and 48 h in severe elevation group was higher than that in normal group and mild moderate elevation group,and the optical density of GMC cells at 12 h,24 h and 48 h in mild moderate elevation group was higher than that in normal group(P<0.05).The optical density of GMC cells in three groups increased gradually with time at 12 h,24 h and 48 h(P<0.05).Compared with the normal group,GMC cells entered s,G2/M phase more significantly in mild,moderate and severe increase groups(P<0.05).The number of GMC cells entering s,G2/M phase in severe elevation group was more than that in mild and moderate elevation group(P<0.05).The expression of mTOR was higher and caspase 3 was lower in mild,moderate and severe increased group than in normal group(P<0.05).The expression of mTOR and caspase 3 in the severe group was higher than that in the mild to moderate group(P<0.05).Conclusion Serum of uremic patients can lead to GMC proliferation,and hyperparathyroidism can promote GMC proliferation and increase the expression of PI3K/Akt/mTOR signaling pathway.PI3K/Akt/mTOR signaling pathway inhibitors may help to inhibit GMC proliferation and delay the process of renal failure in uremic patients.

关 键 词：PI3K/Akt/mTOR信号通路 大鼠肾小球系膜细胞 尿毒症血清 体外增殖 细胞周期时相 CASPASE-3 

分 类 号：R692.5[医药卫生—泌尿科学]