达格列净对慢性肾脏病大鼠的肾脏保护作用及对炎症细胞因子的影响  

Protective effect of dapagliflozin on kidney and its influence on inflammatory cytokinesin rats with chronic kidney disease

作　　者：李雨婷 林钐 王克邪 LI Yuting;LIN Shan;WANG Kexie(Shanghai Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai 200082,China)

机构地区：[1]上海市中西医结合医院,上海200082

出　　处：《现代中西医结合杂志》2024年第17期2379-2383,共5页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：虹口区临床重点专科建设项目(HKLCZD2024A02);2021年度上海市虹口区卫生健康委员会医学科研课题(虹卫2023-01)。

摘　　要：目的观察达格列净对慢性肾脏病大鼠的肾功能和血清炎症细胞因子水平的影响,探讨达格列净的肾脏保护作用及机制。方法将30只雄性Wistar大鼠随机分为对照组、模型组、达格列净组,每组10只。模型组和达格列净组大鼠采用腺嘌呤毒害法建立慢性肾脏病模型,确认造模成功后,达格列净组予以达格列净1.0 mg/(kg·d)灌胃,模型组和对照组予以等量蒸馏水灌胃,均1次/d。持续干预4周后处死大鼠,称量大鼠的肾脏重量,计算肾脏系数,测定24 h尿蛋白定量、空腹血糖及血清肌酐(SCr)、尿素氮(BUN)、总胆固醇(TC)、三酰甘油(TG)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平,HE染色、Masson染色观察大鼠肾脏组织病理形态。结果模型组大鼠肾脏重量、肾脏系数、24 h尿蛋白定量、空腹血糖、SCr、BUN、TC、TG、TNF-α、IL-6水平均明显高于对照组(P均<0.05),达格列净组大鼠的上述各指标均明显低于模型组(P均<0.05)。HE染色显示,模型组大鼠出现肾小球、肾小管及肾间质病变,肾间质可见大量炎性细胞浸润;与模型组比较,达格列净组大鼠肾小球、肾小管及肾间质病变减轻,肾间质偶有少量炎性细胞浸润。Masson染色显示,模型组大鼠肾小管基底膜增厚,部分上皮细胞空泡变性,肾间质大量胶原纤维沉积,出现肾纤维化;与模型组比较,达格列净组大鼠肾间质胶原纤维沉积明显减少,肾小管基底膜增厚、肾纤维化减轻。结论达格列净可能通过降低炎症因子水平,减轻肾脏炎性损伤和纤维化,保护慢性肾脏病大鼠的肾功能。Objective It is to observe the effect of dapagliflozin on renal protection and expression of inflammatory factors in rats with chronic kidney disease,and to explore its renal protective effect and mechanism.Methods Thirty male Wistar rats were randomly divided into control group,model group and dapagliflozin group,with 10 rats in each group.The rats of the model group and dapagliflozin group were used to establish models of chronic kidney disease by adenine toxicity method,after successful modeling,the dapagliflozin group was given dapagliflozin 1.0 mg/(kg·d)by gavage,and the model group and control group were given the same amount of distilled water by gavage,all once daily.After 4 weeks of continuous intervention,the rats were executed,their kidneys were weighed,the renal coefficient was calculated,and the levels of 24-h urine protein,fasting blood glucose,and serum creatinine(SCr),urea nitrogen(BUN),total cholesterol(TC),triacylglycerol(TG),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)were detected,the histopathological morphology of renal tissue in the rats were observed by HE staining and Masson staining.Results The kidney weight,renal coefficient,levels of 24 h urine protein,fasting blood glucose,BUN,SCr,TC,TG,TNF-α,and IL-6 of rats in the model group were significantly higher than those in the control group(all P<0.05),and all of the above indexes of rats in the dapagliflozin group were significantly lower than those in the model group(all P<0.05).HE staining showed that there were glomerular,tubular and interstitial lesions with a large number of inflammatory cells infiltrating the interstitium in the rats of the model group;compared with the model group,the glomerular,tubular and interstitial lesions were alleviated,with occasional small amount of inflammatory cells infiltrating the interstitium in the rats of the dapagliflozin group.Masson staining showed that rats in the model group showed thickening of renal tubular basement membranes,vacuolating degeneration of some epithelial cells,and

关 键 词：慢性肾脏病 肾脏纤维化 达格列净 蛋白尿 炎症细胞因子 

分 类 号：R-332[医药卫生]