首页|卡维地洛对糖尿病肾病小鼠的保护作用及机制研究

卡维地洛对糖尿病肾病小鼠的保护作用及机制研究

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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.
Protective effects and mechanism of carvedilol on diabetic kidney disease in mice
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.

carvediloldiabetic nephropathyrenal functionoxidative stressiron death

吴伟锋、曹莹、冯浩健、吴财能、周平正

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南方医科大学药学院,广东广州 510515

广州中医药大学第一附属医院麻醉科,广东广州 510405

卡维地洛 糖尿病肾病 肾功能 氧化应激 铁死亡

国家自然科学基金广州市基础研究计划基础与应用基础研究基金

82003824202102020071

2024

中国临床药理学杂志
中国药学会

中国临床药理学杂志

CSTPCD北大核心
影响因子:1.91
ISSN:1001-6821
年,卷(期):2024.40(12)
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