利拉鲁肽调控PI3K-Akt-mTOR通路改善糖尿病肾病患者病情

Effect of Liraglutide on PI3K-Akt-mTOR Pathway in Patients with Diabetic Nephropathy

目的针对糖尿病肾病患者应用利拉鲁肽进行干预,从而探讨药物的治疗效果和作用机制。方法选取糖尿病肾病患者,实验组给予利拉鲁肽干预,对照组给予常规治疗,采集各组患者血液及尿液进行血糖、血脂、肾功能、炎性因子、全段成纤维细胞生长因子-23(iFGF-23)以及α-Klotho蛋白含量的检测,提取外周血单个核细胞进行信号通路的检测。结果在血糖方面,与治疗前比较,实验组空腹血糖(FBG)及糖化血红蛋白(HbAlc)含量显著降低(均P<0.05)。在血脂方面,治疗后,相对于对照组,实验组患者总胆固醇(TC),三酰甘油(TG)及低密度脂蛋白胆固醇(LDL-C)含量显著降低,高密度脂蛋白胆固醇(HDL-C)含量显著升高(均P<0.05)。在肾功能方面,相对于对照组,实验组患者血肌酐(Scr),尿微量白蛋白(Umalb)、尿白蛋白/尿肌酐比值(ACR)含量显著降低,肾小球滤过率(GFR)显著升高(均P<0.05)。在炎性因子方面,相对于对照组,实验组TNF-α、IL-1及IL-6含量显著降低(均P<0.05)。在iFGF-23及α-Klotho蛋白含量方面,相对于对照组,实验组患者iFGF-23含量显著降低,α-Klotho含量显著升高(均P<0.05)。信号通路方面,与对照组比较,治疗后实验组患者磷脂酰肌醇(-3)激酶(PI3K),蛋白激酶B(Akt),雷帕霉素靶蛋白(mTOR)含量显著降低(均P<0.05)。结论利拉鲁肽可通过调控PI3K-Akt-mTOR通路改善糖尿病肾病患者病情,为临床用药提供了理论基础。

Objective To investigate the therapeutic effect of liraglutide in patients with diabetic nephropath and related mechanism.Methods The patients in diabetic nephropathy were treated with liraglutide and the control group received routine treatment.The blood and urine of each group were taken to test blood glucose,blood lipid,kidney function,inflammatory factor,total fibroblast growth factor-23（IFGF-23）andα-Klotho protein content.Peripheral blood mononuclear cells were harvested for detection of the signal pathway.Results The contents of FBG and HbAlc in the experimental group were significantly lower than those in before the treatment（both P0.05）.The levels of total cholesterol（TC）,triglyceride（TG）and low density lipoprotein cholesterol（LDL-C）in the experimental group were significantly lower than those in the control group,while the level of HDL-C was significantly increased（all P0.05）.Renal function,serum creatinine（Scr）,urinary microalbuminuria（Umalb）,urinary albumin/creatinine ratio（ACR）were significantly decreased in the experimental group compared with the control group,and the glomerular filtration rate（GFR）was significantly increased（all P0.05）.As for inflammatory cytokines,the levels of TNF-α,IL-1and IL-6in the experimental group were significantly lower than those in the control group（all P0.05）.The content of iFGF-23 in the experimental group was significantly lower than that in the control group（P0.05）,and the level ofα-Klotho was significantly increased（P0.05）.Kinase-3（PI3K）,protein kinase B（Akt）and rapamycin target protein（mTOR）were significantly decreased in the experimental group as compared with those after the treatment in the control group（all P0.05）.Conclusion Liraglutide can improve the condition of diabetic nephropathy by regulating PI3K-Akt-mTOR pathway,which provides a theoretical basis for clinical drug use.