摘要
目的:探讨水陆二仙丹合抵挡汤加减方对糖尿病肾病小鼠线粒体自噬信号通路的影响。方法:将50只db/db小鼠通过简单随机化分为模型组、厄贝沙坦组(0.026 g/kg)、中药低、中、高剂量组(低剂量6.27 g/kg,中剂量为12.74 g/kg,高剂量25.48 g/kg),db/m小鼠10只为正常组,连续灌胃8周。检测各组小鼠血糖(BG)、尿白蛋白/肌酐比值(UACR)、细胞活性氧、肾损伤分子1(KIM-1)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、微管相关轻链蛋白1轻链3(LC3)、PTEN诱导假定激酶1(Pink1)、E3泛素连接酶(Parkin)、沉默信息调节因子1(Sirt1)、过氧化物酶体增殖受体γ辅激活因子α(PGC-1α)以及线粒体融合蛋白(MFN2)表达。结果:与正常组比较,模型组小鼠BG、UACR、KIM-1、NGAL蛋白水平明显升高(P<0.05),Pink1、Parkin、LC3、Sirt1、PGC-1α以及MFN2蛋白表达水平明显下降(P<0.05),线粒体活性氧水平显著升高(P<0.05);与模型组比较,中药低、中、高剂量组和厄贝沙坦组小鼠BG、UACR、KIM-1、NGAL蛋白水平均有不同程度的下降(P<0.05),Pink1、Parkin、LC3、Sirt1、PGC-1α以及MFN2表达水平有不同程度的上升(P<0.05),小鼠线粒体活性氧水平有不同程度的下降(P<0.05)。结论:水陆二仙丹合抵挡汤加减方能够减轻db/db小鼠肾损伤,其机制可能与上调肾脏Sirt1、PGC-1α以及MFN2的表达水平,恢复肾脏线粒体自噬有关。
Objective:To investigate the effects of Shuilu Erxian Pills combined with Didang Decoction with modifications on the mitochondrial autophagy signaling pathway in diabetic nephropathy(DN) mice.Methods:Fifty db/db mice were randomly divided into a model group,an irbesartan group(0.026 g/kg),and low-,medium-,and high-dose Chinese medicine groups(6.27,12.74,and 25.48 g/kg).An additional 10 db/m mice served as the normal control group.All groups received continuous intragastric administration for 8 weeks.Blood glucose(BG),urinary albumin-to-creatinine ratio(UACR),reactive oxygen species(ROS),kidney injury molecule-1(KIM-1),neutrophil gelatinase-associated lipocalin(NGAL),and expression levels of LC3,PTEN-induced putative kinase 1(Pink1),E3 ubiquitin ligase(Parkin),sirtuin 1(Sirt1),peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α),and mitofusin 2(MFN2) were measured.Results:Compared with the normal group,the model group showed significantly increased BG,UACR,KIM-1,and NGAL protein levels(P<0.05),decreased expression of Pink1,Parkin,LC3,Sirt1,PGC-1α,and MFN2 proteins(P<0.05),and increased mitochondrial reactive oxygen species level(P<0.05).Compared with the model group,the low-,medium-,and high-dose Chinese medicine groups and the irbesartan group showed decreased BG,UACR,KIM-1,and NGAL protein levels to varying degrees(P<0.05),increased expression of Pink1,Parkin,LC3,Sirt1,PGC-1α,and MFN2 proteins(P<0.05),and reduced mitochondrial ROS levels(P<0.05).Conclusion:Shuilu Erxian Pills combined with Didang Decoction with modifications alleviates kidney injury in db/db mice,possibly by upregulating the expression of Sirt1,PGC-1α,and MFN2 in renal tissue and restoring mitochondrial autophagy.
作者
张园
祁彤
高飞
刘慧
纪品川
张亚超
高占华
孔令娟
常柏
郭建恩
ZHANG Yuan;QI Tong;GAO Fei;LIU Hui;JI Pinchuan;ZHANG Yachao;GAO Zhanhua;KONG Lingjuan;CHANG Bai;GUO Jian′en(Chengde Medical University,Chengde 067000,China;Chaoyang District Traditional Chinese Medicine Hospital,Beijing 100020,China;Chengde Hospital of Traditional Chinese Medicine,Chengde 067000,China;Tianjin Medical University Chu Hsien-I Memorial Hospital,Tianjin 300134,China)
出处
《世界中医药》
北大核心
2025年第6期924-931,共8页
World Chinese Medicine
基金
国家自然科学基金项目(81973614)
河北省自然科学基金资助项目(H2022406069)
2024年河北省硕士在读研究生创新能力培养资助项目(CXZZSS2024124)。
