摘要
糖尿病肾病(diabetic kidney disease,DKD)已经成为晚期终末期肾病的主要诱因,该病在临床上的药物治疗仍然有一定的局限性。该研究旨在探究冠心丹参方对db/db小鼠糖尿病肾病的治疗作用及其分子机制。将db/m和db/db小鼠随机分为对照组(db/m)、模型组、二甲双胍组、冠心丹参方组。药物干预8周后,各实验组动物分别眼球取血,处死取材,检测相关生化指标和肾脏组织病理学变化。结果显示,与模型组相比,冠心丹参方可显著降低db/db小鼠甘油三酯(TG)、总胆固醇(TCH)和低密度脂蛋白(LDL)的水平(P<0.05);苏木精-伊红(HE)染色和高碘酸-希夫(PAS)染色显示,冠心丹参方可显著改善db/db小鼠肾小球体积增大和基底膜增厚,减轻肾小球内系膜增生;还能降低db/db小鼠血清肌酐和血尿素氮的水平;冠心丹参方可显著提高糖尿病小鼠肾脏组织内抗氧化酶谷胱甘肽过氧化物酶(GSH-Px)水平,降低乳酸脱氢酶(LDH)和丙二醛(MDA)的水平;Western blot结果显示,冠心丹参方可显著提高db/db小鼠雌激素受体α(ERα)和磷酸化蛋白激酶B(p-Akt)的蛋白水平,促进核因子E2相关因子2(Nrf2)及其调控血红素加氧酶-1(HO-1)的蛋白表达。冠心丹参方可能通过上调ERα及其下游Nrf2介导的抗氧化酶HO-1水平发挥治疗糖尿病肾病的作用。
Diabetic kidney disease(DKD)has become a primary cause of end-stage kidney disease,without any effective treatment available.In this study,we assessed the protective effect of Guanxin Danshen Formulation(GXDSF)on diabetic nephropathy in db/db mice.The db/m and db/db mice were randomly divided into 4 groups:control group,model group,metformin group,and GXDSF group.After 8 weeks′treatment with GXDSF,metformin or normal saline,the mice were sacrificed,and the blood and kidney tissues were collected for the further analysis.Compared with the model group,TG,TCH and LDL levels significantly decreased in the GXDSF group.The results from HE and PAS staining showed that db/db mice exhibited abnormal kidney tissues with increased glomerular volume,basement-membrane thickening and mesangial cell proliferation,which could be significantly alleviated by GXDSF treatment.GXDSF treatment also reduced serum creatinine and BUN.Meanwhile,GXDSF treatment markedly elevated GSH-PX levels,while reduced LDH and MDA levels in the kidney tissues.Western blot assay showed that GXDSF evidently up-regulated protein levels of ERαand p-Akt,and subsequently promoted HO-1 expression mediated by Nrf2.These data collectively indicated that GXDSF protects db/db mice against DN by regulating ERαand Nrf2-mediated HO-1 expression.
作者
张彬
张雪涟
张晨阳
孙桂波
孙晓波
ZHANG Bin;ZHANG Xue-lian;ZHANG Chen-yang;SUN Gui-bo;SUN Xiao-bo(Institute of Medicinal Plant Development,Peking Union Medical College and Chinese Academy of Medical Sciences,Beijing 100193,China;Key Laboratory of New Drug Discovery based on Classic Chinese Medicine Prescription,Chinese Academy of Medical Sciences,Beijing 100193,China;Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders,State Administration of Traditional Chinese Medicine,Beijing 100193,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2020年第11期2595-2600,共6页
China Journal of Chinese Materia Medica
基金
中国医学科学院重点实验室课题(2018PT35030)
国家重点研发计划项目(2018YFC1707408)
国家“重大新药创制”科技重大专项(2018ZX0971101-009)
国家自然科学基金项目(81891012)。
关键词
冠心丹参方
糖尿病肾病
氧化应激
糖尿病
雌激素受体
Guanxin Danshen Formulation
diabetic kidney disease(DKD)
oxidative stress
diabetes mellitus
estrogen receptor
