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水蛭素对糖尿病肾病模型小鼠的作用机制研究

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目的 本研究旨在探讨水蛭素对糖尿病肾病模型小鼠的治疗作用及机制。方法 采用高脂饮食和腹腔注射链脲佐菌素制备糖尿病肾病小鼠模型,将模型小鼠随机分为模型组和水蛭素治疗组。治疗组小鼠给予水蛭素灌胃,连续8周。观察小鼠肾功能指数、尿液指标、炎症因子及炎性蛋白表达水平的变化。结果 小鼠造模后,血糖水平显著提高,出现明显肾损伤,说明造模成功。水蛭素治疗后,血尿素氮(BUN)、血清肌酐(CREA)和尿白蛋白与肌酐比值(UACR)水平均显著降低,尿液β2-微球蛋白(β2-MG)和尿肌酐(UCr)水平均显著改善,肾皮质中炎症因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和MCP-1的浓度均明显降低。进一步的蛋白印迹实验表明,水蛭素可以显著抑制NLRP3和TLR4蛋白的表达水平。结论 水蛭素对糖尿病肾病小鼠有治疗作用,其机制可能与抗炎作用有关。
Study on the mechanism of hirudin on diabetes nephropathy model mice
Objective To investigate the therapeutic effect and mechanism of hirudin on diabetes nephropathy in mice.Methods Diabetic nephropathy mouse model was established by high-fat diet and intraperitoneal injection of streptozotocin,and the model mice were randomly divided into model group and hirudin treatment group.Mice in the treatment group were given hirudin by gavage for 8 weeks.The changes of renal function index,urine index,inflammatory factors and inflammatory protein expression in mice were observed.Results After modeling in mice,blood glucose levels significantly increased and significant kidney damage occurred,indicating successful modeling.After hirudin treatment,the levels of blood urea nitrogen(BUN),serum creatinine(CREA)and urinary albumin to creatinine ratio(UACR)decreased significantly,the levels of urine β2-microglobulin(β2-MG)and urinary creatinine(UCr)improved significantly,and the concentrations of inflammatory factors interleukin-1β(IL-1β),interleukin-6(IL-6)and MCP-1 in renal cortex decreased significantly.Further western blot experiments showed that hirudin could significantly inhibit the expression levels of NLRP3 and TLR4 proteins.Conclusion Hirudin has therapeutic effect on diabetic nephropathy mice,and its mechanism may be related to anti-inflammatory effect.

HirudinDiabetic nephropathyInflammatory factorStreptozocin

谷海林、张效丽、聂鑫、盖辉、王瑞

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山东大学齐鲁医院,山东济南 250012

山东中医药大学附属医院,山东济南 250014

济南三源药业有限公司,山东济南 250200

山东省中医药研究院,山东济南 250014

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水蛭素 糖尿病肾病 炎性因子 链脲霉素

山东省中医药科技项目山东省科技型中小企业创新能力提升工程项目

2021M1972023TSGC0301

2024

中国医药科学
海峡两岸医药卫生交流协会 二十一世纪联合创新(北京)医药科学研究院

中国医药科学

影响因子:1.083
ISSN:2095-0616
年,卷(期):2024.14(15)