补阳还五汤通过抑制炎症和凋亡改善糖尿病小鼠心肌损伤  

Protective effect of Buyang Huanwu Decoction on cardiac damage in diabetic mice by inhibiting inflammation and apoptosis

作　　者：田小超 杨帆[1] 马赟 娄菲菲[4] 刘玉 刘素云 陈志强[3] TIAN Xiaochao;YANG Fan;MA Yun;LOU Feifei;LIU Yu;LIU Suyun;CHEN Zhiqiang(Hebei University of Chinese Medicine,Shijiazhuang 050013,China;The Second Hospital of Hebei Medical University,Shijiazhuang 050000,China;The First Affiliated Hospital of Hebei University of Chinese Medicine/Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050011,China;Hebei General Hospital,Shijiazhuang 050051,China)

机构地区：[1]河北中医药大学,石家庄050013 [2]河北医科大学第二医院,石家庄050000 [3]河北中医药大学第一附属医院/河北省中医院,石家庄050011 [4]河北省人民医院,石家庄050051

出　　处：《中华中医药杂志》2024年第12期6700-6706,共7页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.82274504);河北省重点研发计划项目(No.20377711D,No.192777104D);河北省自然科学基金项目(No.H2023206203);河北省中医药管理局科研计划项目(No.2024038);河北省医学科学研究课题计划(No.20230474)。

摘　　要：目的:探讨补阳还五汤对糖尿病心肌病(DCM)小鼠心肌组织保护作用及炎症和凋亡因子的影响。方法:30只7~8周龄db/db小鼠饲养至10周使其发展为DCM并随机分为模型组、补阳还五汤组、舒洛地特组,每组10只。7~8周龄db/m组小鼠10只作为对照组。给予相应药物治疗12周后,检测小鼠血糖(FBG)、肌酸激酶同工酶(CK-MB)、白细胞介素-6(IL-6)、单核细胞趋化因子-1(MCP-1)、肿瘤坏死因子-α(TNF-α)、甘油三脂(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平;qRT-PCR检测Toll样受体4(TLR4)、核转录因子-κB p65(NF-κB p65)mRNA表达;Western Blot检测小鼠心脏组织TLR4、NF-κB p65、Cleaved caspase-3和Cleaved PARP蛋白表达;免疫组化检测心脏组织TLR4、NF-κB p65、Ⅰ型胶原蛋白、Ⅲ型胶原蛋白表达;HE、Masson和天狼星红染色观察心脏病理形态学变化。结果:与对照组比较,模型组小鼠心肌纤维数量明显减少,心肌组织排列紊乱,胶原纤维明显增多;血清FBG、CK-MB、IL-6、MCP-1、TNF-α、TG、LDL-C含量显著升高(P<0.01,P<0.05),HDL-C水平显著降低(P<0.01),TNF-α、IL-6、MCP-1显著升高(P<0.01);心脏组织TLR4、NF-κB p65、Cleaved caspase-3、Cleaved PARP、Ⅰ型胶原蛋白、Ⅲ型胶原蛋白表达显著增强(P<0.01,P<0.05)。与模型组比较,补阳还五汤干预后,DCM小鼠心脏病理损伤程度明显改善;血清CK-MB、IL-6、MCP-1、TNF-α、TG、LDL-C水平显著下降(P<0.01,P<0.05),HDL-C水平显著上调(P<0.05),TNF-α、IL-6、MCP-1显著降低(P<0.01,P<0.05);心肌组织TLR4、NF-κB p65、Cleaved caspase-3、Cleaved PARP、Ⅰ型胶原蛋白、Ⅲ型胶原蛋白表达显著降低(P<0.01,P<0.05)。结论:补阳还五汤可通过抑制TLR4/NF-κB通路及促凋亡因子表达,对DCM小鼠发挥抗炎和抗凋亡作用,减轻心脏病理损伤,从而发挥心脏保护作用。Objective:To explore the protective effect of Buyang Huanwu Decoction on myocardial tissue and the influence of inflammatory and apoptotic factors in mice with diabetes cardiomyopathy(DCM).Methods:A total of 30 db/db mice(7-8 weeks old)were raised for 10 weeks to develop DCM and randomly divided into model group,Buyang Huanwu Decoction group,and Shuluodite group,with 10 mice in each group.Another 10 db/m mice(7-8 weeks old)were included in the control group.Corresponding medication treatment were provided for 12 weeks,the levels of blood glucose(FBG),creatine kinase isoenzyme(CK-MB),interleukin-6(IL-6),monocyte chemokine 1(MCP-1),tumor necrosis factor-α(TNF-α),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)were detected.The mRNA expression of Toll like receptor(TLR4)and nuclear transcription factor-κB p65(NF-κB p65)were detected by qRT-PCR.Western Blot was used to detect the expression of TLR4,NF-κB p65,Cleaved caspase-3 and Cleaved PARP in mouse cardiac tissue.Immunohistochemical was used to detect the expression of TLR4,NF-κB p65,I and III collagen in cardiac tissue.HE,Masson,and Sirius red staining were used to observe the pathological and morphological changes of the heart.Results:Compared with the control group,the model group mice showed a significant decrease in the number of myocardial fibers,disordered arrangement of myocardial tissue and a significant increase in collagen fibers,the contents of FBG,CK-MB,IL-6,MCP-1,TNF-α,TG,LDL-C were significantly increased(P<0.01,P<0.05),while the HDL-C levels was decreased(P<0.01),TNF-α,IL-6,and MCP-1 were significantly elevated(P<0.01),at the same time,the expression of TLR4,NF-κB p65,Cleaved caspase-3,Cleaved PARP,and I and III collagen proteins was significantly enhanced in cardiac tissue(P<0.01,P<0.05).Compared with the model group,after intervention with Buyang Huanwu Decoction,the degree of cardiac pathological damage was significantly improved in DCM mice,the levels of CK-MB,IL-6,MCP-1,TNF-�

关 键 词：糖尿病心肌病 补阳还五汤 炎症反应 细胞凋亡 Toll样受体4/核转录因子-κB信号通路 机制 心肌损伤 

分 类 号：R54[医药卫生—心血管疾病]