达格列净联合雷公藤多甙对2型糖尿病肾病患者血清氧化应激状态、纤维化指标变化及Klotho蛋白表达的影响研究  

A study on the effects of dapagliflozin combined tripterygium glycosides with on serum oxidative stress status,fibrosis markers,and Klotho protein expression in patients with diabetic nephropathy

作　　者：李吉 白寿军 曲晓蕾 姬婷婷 Li Ji;Bai Shoujun;Qu Xiaolei;et al(Department of Nephrology,Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University,Shang Hai 201700,China)

机构地区：[1]复旦大学附属中山医院青浦分院肾内科,上海201700

出　　处：《中华保健医学杂志》2025年第1期115-119,共5页Chinese Journal of Health Care and Medicine

基　　金：青浦区卫生健康系统第四轮人才培养项目(WY2019-63);青浦区卫生健康系统第五轮学科建设和人才培养项目(TX2023-26)。

摘　　要：目的评估达格列净联合雷公藤多甙对2型糖尿病肾病的临床效果,探究其对血清Klotho蛋白、纤维化指标及氧化应激指标的影响。方法采用前瞻性研究,纳入2020年1月~2023年5月复旦大学附属中山医院青浦分院116例2型糖尿病肾病患者,随机数表法分为达格列净组和联合用药组(达格列净联合雷公藤多甙),各60例。比较分析两组治疗前后的24 h蛋白尿量、Klotho蛋白、转化生长因子-β1(TGF-β1)、结缔组织生长因子(CTGF)、超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)的变化及血糖、体质量指数、肝功能、不良反应情况。结果治疗后,两组患者的24 h蛋白尿量均有所改善,且联合用药组改善程度更显著,差异有统计学意义(t=11.315,P<0.05)。血清Klotho蛋白水平两组均升高,但联合用药组升幅更大,差异有统计学意义(t=31.981,P<0.05);纤维化指标TGF-β1、CTGF及氧化应激指标MDA均显著降低,联合用药组降幅更显著,差异均有统计学意义(t=27.728、14.148、10.609,P<0.05);抗氧化酶SOD、GSH-Px水平均显著升高,联合用药组升幅更大,差异均有统计学意义(t=11.587、10.790,P<0.05)。采用Pearson相关分析,治疗前后Klotho蛋白与24 h蛋白尿量、TGF-β1、CTGF、MDA水平呈负相关(r=-0.365、-0.278、-0.327、-0.419,P<0.05),与SOD、GSH-Px水平呈正相关(r=0.256、0.334,P<0.05)。治疗后,联合用药组空腹血糖、餐后2 h血糖、体质量指数及糖化血红蛋白均低于达格列净组,差异均有统计学意义(t=2.162、19.449、2.215、5.358,P<0.05)。治疗后,两组丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)组间比较差异无统计学意义(t=4.804、5.070,P>0.05)。两组不良反应发生率比较差异无统计学意义(χ^(2)=0.152,P>0.05)。结论达格列净联合雷公藤多甙治疗2型糖尿病肾病可显著降低患者蛋白尿量,延缓肾功能恶化,可能通过上调Klotho蛋白、抑制肾间质纤维化及缓解氧化应Objective To assess the clinical impact of dapagliflozin in combination with tripterygium wilfordii glycosides on patients with type 2 diabetic nephropathy,and to investigate its effects on serum Klotho protein levels,fibrosis markers,and oxidative stress indicators.Methods A prospective study was conducted in 116 patients with type 2 diabetic nephropathy in the Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University,who were randomly divided into a combination group(dagaglizin combined with tripterygium glycoside)and a control group(daglizin alone).The 24-hour albuminuria,Klotho protein and Transforming growth factor beta 1 before and after treatment were compared between the two groups.transforming growth factor beta 1(TGF-β1),connective tissue growth factor(CTGF),superoxide dismutase(SOD),malondialdehyde(MDA)changes of and glutathione peroxidase(GSH-Px),blood glucose,body mass index,liver function and adverse reactions in oxidase.Result Post-treatment,both groups experienced improvements in 24-hour proteinuria,with the combination group showing a more significant degree of improvement(t=11.315,P<0.05).Serum Klotho protein level was increased in both groups,but the increase was greater in the combined treatment group(t=31.981,P<0.05).The fibrosis index TGF-β1,CTGF and oxidative stress index MDA were significantly decreased,and the decrease was more significant in the combined treatment group(t=27.728,14.148,10.609,P<0.05).The levels of antioxidant enzymes SOD and GSH-Px were significantly increased,and the increases were more prominent in the combined treatment group(t=11.587,10.790,P<0.05).Pearson correlation analysis showed that Klotho protein was negatively correlated with 24 h albuminuria,TGF-β1,CTGF and MDA levels before and after treatment(r=-0.365,-0.278,-0.327,-0.419,P<0.05).It was positively correlated with SOD and GSH-Px levels(r=0.256,0.334,P<0.05).After treatment,fasting blood glucose,2 h postmeal blood glucose,body mass index and HBA1c in the combined treatment group were lower than t

关 键 词：达格列净 雷公藤多甙 2型糖尿病肾病 血清Klotho蛋白 肾间质纤维化 

分 类 号：R587.2[医药卫生—内分泌]