荭草素通过调控NNMT、SIRT1蛋白表达保护db/db糖尿病小鼠肾脏损伤

摘要

目的 探究荭草素是否通过调控NNMT、SIRT1蛋白表达保护db/db糖尿病小鼠肾脏损伤。方法 db/db小鼠随机分组：模型组、低剂量荭草素干预组（10 mg·kg^-1）、高剂量荭草素干预组（40 mg·kg^-1）、洛汀新干预组（0.9 mg·kg^-1）,每组6只;另外以6只同龄db/m小鼠作为正常对照组。各组小鼠灌胃治疗时间均为4周。给药期间检测各组小鼠空腹血糖（FBG）;给药结束后检测小鼠血清肌酐（CREA）、尿素（UREA）、尿酸（UA）及尿液微量白蛋白（MALB）含量;取肾脏,HE染色观察肾脏形态结构,PAS染色、Masson染色分别观察肾脏糖原沉积情况和纤维化情况;WB法检测肾脏烟酰胺N-甲基转移酶（NNMT）、沉默信息调节因子2相关酶1（SIRT1）蛋白表达情况。结果 与模型组相比,采用荭草素干预治疗能有效降低db/db小鼠FBG,血清CREA、UREA、UA含量和尿液MALB含量,减轻肾脏炎症反应、纤维化程度和糖原沉积;与模型组相比,采用荭草素干预治疗能显著降低小鼠肾脏NNMT蛋白表达,增加SIRT1蛋白表达。结论 荭草素对db/db糖尿病小鼠肾脏损伤具有一定保护作用,其机制可能与下调NNMT蛋白表达、上调SIRT1蛋白表达有关。

关键词

荭草素 / 糖尿病肾病 / db/db小鼠 / NNMT / SIRT1 / 肾脏保护

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基金资助

福建省自然科学基金（2024J011585,2024J011586）; 漳州市自然科学基金（ZZ2023J09）; 全国老药工传承工作室建设项目（国中医药人教函【2024】255号）