卡维地洛对糖尿病肾病小鼠的保护作用及机制研究
Protective effects and mechanism of carvedilol on diabetic kidney disease in mice
吴伟锋 1曹莹 1冯浩健 1吴财能 2周平正1
作者信息
- 1. 南方医科大学药学院,广东广州 510515
- 2. 广州中医药大学第一附属医院麻醉科,广东广州 510405
- 折叠
摘要
目的 观察卡维地洛对糖尿病肾病(DKD)小鼠肾功能的影响,并初步研究其作用机制.方法 将C57BL/6J雄性小鼠随机分为对照组、模型组和实验组,每组10只.模型组和实验组小鼠用腹腔注射150 mg·kg-1链脲菌佐素(STZ)的方法构建小鼠Ⅰ型糖尿病模型.模型构建成功后,实验组小鼠灌胃给予10 mg·kg-1·d-1卡维地洛,对照组和模型组给予等量0.9％NaCl.实验过程中每周监测小鼠空腹血糖(FBG).给药8周后,检测小鼠尿液中的白蛋白肌酸酐比(UACR)、尿酸(UA)含量、肾组织铁(Fe)、超氧化物歧化酶(SOD)和丙二醛(MDA)的水平.同时,对肾组织进行苏木精-伊红(HE)染色、马松(Masson)染色观察病理学改变.结果 给药8周后,对照组、模型组和实验组的UACR分别为(12.43±1.13)、(63.01±20.78)和(19.79±1.94)mg·mmol-1,UA 含量分别为(132.10±10.14)、(174.40±7.06)和(135.00±3.95)μmol·L-1,Fe 水平分别为(7.49±0.81)、(9.98±0.46)和(7.02±0.60)μmol·g prot-1,SOD 活性分别为(34.56±0.58)、(30.27±1.22)和(34.43±1.36)U·mg prot-1,MDA含量分别为(5.49±0.31)、(7.72±0.17)和(4.46±0.32)nmol·mg prot-1.模型组与对照组比较,在统计学上差异均有统计学意义(均P＜0.05);实验组与模型组比较,在统计学上差异均有统计学意义(均P＜0.05).结论 卡维地洛可以减轻糖尿病小鼠肾功能的损伤,其机制可能与通过抑制铁死亡,减轻氧化应激损伤的发生有关.
Abstract
Objective To observe the effects of carvedilol on renal function in mice with diabetic kidney disease(DKD)and to preliminarily study its mechanism of action.Methods C57BL/6J male mice were randomly divided into control group,model group and experimental group,with 10 mice in each group.The mouse model of type Ⅰ diabetes was established by intraperitoneal injection of 150 mg·kg-1 streptozotocin(STZ).After successful modeling,the experimental group mice were given 10 mg·kg-1·d-1 carvedilol by gavage,while the control group and model group were given equal amounts of 0.9％NaCl.During the experiment,the fasting blood glucose(FBG)of mice were monitored weekly.After 8 weeks of administration,the urinary albumin to creatinine ratio(UACR),uric acid(UA),and other contents in the urine of mice were detected,as well as the levels of iron(Fe),superoxide dismutase(SOD),and malondialdehyde(MDA)in the renal tissue.And hematoxylin-eosin(HE)and Masson staining were performed on the renal tissue to observe the pathological changes of the kidney.Results After 8 weeks of administration,the UACR of the control group,model group and experimental group were(12.43±1.13),(63.01±20.78)and(19.79±1.94)mg·mmol-1;the UA levels were(132.10±10.14),(174.40±7.06)and(135.00±3.95)μmol·L-1;the Fe levels were(7.49±0.81),(9.98±0.46)and(7.02±0.60)μmol·g prot-1;the SOD activities were(34.56±0.58),(30.27±1.22)and(34.43±1.36)U·mg prot1;the MDA contents were(5.49±0.31),(7.72±0.17)and(4.46±0.32)nmol·mg prot-1.The differences between model group and normal group were statistically significant(all P＜0.05);compared between experimental group and model group,the difference were significant(all P＜0.05).Conclusion Carvedilol can alleviate the damage of renal function in diabetes mice,and its mechanism may be related to inhibiting iron death and alleviating oxidative stress injury.
关键词
卡维地洛/糖尿病肾病/肾功能/氧化应激/铁死亡Key words
carvedilol/diabetic nephropathy/renal function/oxidative stress/iron death引用本文复制引用
基金项目
国家自然科学基金(82003824)
广州市基础研究计划基础与应用基础研究基金(202102020071)
出版年
2024
国家科技期刊平台
NSTL
万方数据