摘要
目的探讨丹参酮ⅡA(TanⅡA)对大鼠糖尿病肾脏疾病(DKD)的保护作用及机制。方法高脂饮食联合链脲佐菌素注射液(STZ)复制大鼠DKD模型。将实验动物分为对照组、模型组、TanⅡA组、缬沙坦组。实验过程中动态检测各组大鼠的体重、血糖变化,收集血、尿标本检测生化指标;收集肾组织进行苏木精-伊红染色(HE)、过碘酸雪夫染色(PAS)、透射电镜以及免疫组化检测。结果TanⅡA可增加DKD大鼠体重(P<0.01),降低血尿素氮(BUN)、24 h尿蛋白和血清肌酐(Scr)水平(P<0.05),而用药各组空腹血糖(FBG)差异无统计学意义。TanⅡA组肾组织HE染色后肾小管损伤分级、PAS阳性的肾小球系膜区统计均较DKD组减轻(P<0.05)。TanⅡA改善DKD大鼠的氧化应激与细胞焦亡:透射电镜观察到TanⅡA组和缬沙坦组大鼠肾小球微血管内皮细胞(RGMEC)的细胞膜损伤明显减轻;TanⅡA组和缬沙坦组的硫氧还蛋白相互作用蛋白(Txnip)、含NLR家族Pyrin域蛋白3(Nlrp3)表达减少(P<0.01)。结论丹参酮ⅡA可以通过调节Txnip/Nlrp3炎症小体,抑制大鼠肾小球微血管内皮细胞焦亡,从而延缓DKD的进展。
Objective To investigate the protective effects and mechanisms of TanshinoneⅡA(TanⅡA)on diabetic kidney disease(DKD)in rats.Methods A rat model of DKD was established using a high-fat diet combined with streptozocin(STZ)injections.The experimental animals were divided into control group,model group,TanⅡA group,and valsartan group.During the experiment,the alterations in body weight and blood glucose levels of each cohort of rats were continuously monitored,blood and urine samples were collected for biochemical markers analysis.Kidney tissues were collected for Hematoxylin-Eosin(HE)staining,Periodic Acid Schiff(PAS),transmission electron microscopy,and immunohistochemical detection.Results TanⅡA was found to increase the body weight of DKD rats(P<0.01),decrease the blood urea nitrogen(BUN),24-hour urinary protein,and serum creatinine(Scr)levels(P<0.05),with no significant differences in fasting blood glucose(FBG)among the drug groups.Moreover,the renal tubular injury score after HE staining and the count of PAS-positive mesangial areas in glomeruli in TanⅡA group were both reduced compared to the DKD group(P<0.05).TanⅡA effectively improved oxidative stress and pyroptosis in rats with DKD.Transmission electron microscopy showed that the cell membrane damage in glomerular microvascular endothelial cells(RGMEC)of the TanⅡA and valsartan groups was significantly reduced.The expression of Txnip and Nlrp3 were significantly decreased in the TanⅡA and valsartan group(P<0.01).Conclusions TanⅡA has been observed to potentially delay the progression of DKD by inhibiting glomerular microvascular endothelial cell pyroptosis in rats through regulating Txnip/Nlrp3 inflammasome.
作者
张珂嘉
周子铉
高坤
孙斯凡
刘超侠
ZHANG Kejia;ZHOU Zixuan;GAO Kun;SUN Sifan;LIU Chaoxia(Public Experimental Research Center of Xuzhou Medical University,Xuzhou,Jiangsu 221004,China;School of Nursing,Xuzhou Medical University;Jiangsu Provincial Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Traditional Chinese Medicine,Nanjing,Jiangsu 210000;Department of Pathophysiology,School of Basic Medicine,Xuzhou Medical University)
出处
《徐州医科大学学报》
CAS
2024年第1期1-5,共5页
Journal of Xuzhou Medical University
基金
国家中医药管理局青年岐黄学者支持项目
南京中医药大学附属江苏省中医院院级高峰人才项目(y2021yrc30)。
