摘要
目的研究葛根素(puerarin,PR)对糖尿病小鼠心肌损伤的保护作用及机制。方法随机选取8只雄性C57BL/6J小鼠作为对照组,剩下的小鼠通过腹腔注射链脲佐菌素(STZ)构建糖尿病模型,造模成功的小鼠随机分为模型组、PR高、中、低剂量组、焦亡抑制剂(NSA)组和焦亡诱导剂(Nigericin)组,连续给药12周。末次给药结束后取小鼠血清和心脏组织,观察小鼠心肌的变化,检测血清中乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)含量,检测小鼠心肌组织中焦亡相关因子(NLRP3、caspase-1、GSDMD、IL-18、IL-1β)的蛋白和mRNA表达情况。结果与正常组相比,模型组小鼠心肌组织肿胀、扭曲,心肌排列紊乱,胶原纤维增多,血清中LDH、CK-MB含量增加、心肌组织中焦亡相关因子的表达均明显增高(P<0.05或P<0.01)。与模型组相比,PR及NSA组小鼠心肌组织病理变化明显改善,血清LDH、CK-MB含量明显降低,心肌组织中焦亡相关因子的表达得到明显抑制(P<0.05或P<0.01),Nigericin组未见明显改变。结论PR对糖尿病小鼠的心肌损伤具有保护作用,其机制可能与抑制NLRP3/caspase-1/GSDMD焦亡信号通路有关。
Aim To study the protective effect of puerarin(PR)on myocardial injury in diabetic mice and to explore the related mechanism.Methods Eight male C57BL/6J mice were randomly selected as the control group,and the remaining mice were randomly injected with streptozotocin(STZ)to construct a diabetes model,and the mice that were successfully modeled were randomly divided into the model group,PR high,medium and low dose groups,pyroptosis inhibitor(NSA)group and pyroptosis inducer(Nigericin)group,which were administered continuously for 12 weeks.After the last dose,the serum and heart tissues of mice were taken to observe the changes of myocardium,the contents of lactate dehydrogenase(LDH)and creatine kinase isoenzyme(CK-MB)in the serum were detected,and the protein and mRNA expressions of pyroptosis-related factors(NLRP3,caspase-1,GSDMD,IL-18,IL-1β)in myocardial tissues of mice were detected.Results Compared with the control group,the model group had swollen and twisted myocardial tissue,myocardial arrangement disorder,increased collagen fibers,increased content of LDH and CK-MB in serum,and significantly increased the expression of pyroxosis related factors in myocardial tissue(P<0.05 or P<0.01).Compared with the model group,the pathological changes of myocardial tissue in in the PR and NSA groups were significantly improved,the content of serum LDH and CK-MB was significantly reduced,and the expression of pyroxosis related factors in myocardial tissue was significantly inhibited(P<0.05 or P<0.01),while there was no significant change in the Nigericin group.Conclusions PR has a protective effect on myocardial injury in diabetic mice,and its mechanism may be related to the inhibition of the NLRP3/caspase-1/GSDMD pyrosis signaling pathway.
作者
陈秋燕
王璐
黄仁彬
徐小惠
CHEN Qiu-yan;WANG Lu;HUANG Ren-bin;XU Xiao-hui(Dept of Pharmacy,Guangxi Medical University Cancer Hospital,Guangxi Medical University,Nanning 530021,China;School of pharmacy,Guangxi Medical University,Nanning 530021,China)
出处
《中国药理学通报》
北大核心
2025年第7期1259-1264,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 82104558)
广西自然科学基金资助项目(No 2023GXNSFAA026205,2023GXNSF AA026214)。
