红景天苷对心肌缺血-再灌注损伤大鼠内质网应激与Cx43的作用  

Effect of Salidroside on Endoplasmic Reticulum Stress and Connexin 43 in Rats with Myocardial Ischemia Reperfusion Injury

作　　者：黄媛恒[1] 何阳 黄晓亮[2] 韦学 吴耀生[1] 李映新[2] HUANG Yuanheng;HE Yang;HUANG Xiaoliang;WEI Xue;WU Yaosheng;LI Yingxin(School of Basic Medical Science,Guangxi Medical University,Nanning 530021,China;Pharmaceutical College,Guangxi Medical University,Nanning 530021,China;Department of Pharmacy,Hezhou People's Hospital,Hezhou 542899,China)

机构地区：[1]广西医科大学基础医学院,南宁530021 [2]广西医科大学药学院,南宁530021 [3]贺州市人民医院药学部,贺州542899

出　　处：《医药导报》2025年第3期366-371,共6页Herald of Medicine

基　　金：广西一流学科(药学)建设项目(GXFCDP-PS-2018)资助下的广西医科大学药学院青年基金项目;广西一流学科(基础医学)建设项目(GXFCDP-BMS-2018)资助下的广西医科大学基础医学院基础医学科技创新培育基金项目。

摘　　要：目的研究红景天苷(Sal)对心肌缺血-再灌注损伤(MIRI)大鼠内质网应激和缝隙连接蛋白43(Cx43)的作用。方法将SD大鼠随机分为假手术组(Sham)、MIRI组、Sal小剂量组(Sal-L)、Sal大剂量组(Sal-H)。Sham组与MIRI组腹腔注射0.9%氯化钠溶液10 mL·kg^(-1)·d^(-1);Sal-L组与Sal-H组腹腔注射Sal12、36 mg·kg^(-1)·d^(-1)。均每天1次,连续3 d。末次给药30 min后,除Sham组外,其余组制备MIRI模型。苏木精-伊红(HE)染色观察心肌组织病理改变,原位末端转移酶标记技术(TUNEL)测定细胞凋亡率,实时定量基因扩增荧光检测系统(q-PCR)与蛋白印迹法(Western blotting)检测葡萄糖调节蛋白78(GRP78)、半胱氨酸天冬氨酸蛋白酶12(Caspase12)、CCAAT/增强子结合蛋白同源蛋白(CHOP)等内质网应激相关因子以及Cx43的基因及蛋白表达。结果与MIRI组比较,Sal各剂量组心肌损伤不同程度减轻,Sal-H组心肌细胞凋亡率降低(P<0.05);Sal各剂量组Cx43基因表达均上调,GRP78、Caspase12、CHOP基因表达下调;Sal各剂量组Cx43蛋白表达均上调、GRP78蛋白表达下调,Sal-H组CHOP、Bax、Caspase12、cleaved-Caspase3蛋白表达下调,Bcl-2蛋白表达上调(P<0.05)。结论红景天苷对心肌细胞具有保护作用,其机制可能与抑制内质网应激所致细胞凋亡和Cx43代谢失衡有关。Objective To explore the effect of salidroside(Sal)on endoplasmic reticulum stress and connexin 43 in rats with myocardial ischemia-reperfusion injury(MIRI).Methods SD rats were randomly divided into Sham group,MIRI group,low-does Sal(Sal-L)group and high-does Sal(Sal-H)group.The Sham group and MIRI group were intraperitoneal injected with 0.9%sodium chloride solution(10 mL·kg^(-1)·d^(-1)),the Sal-L group and Sal-H group were intraperitoneal injected at a volume of 10 mL·kg^(-1)with Sal(12,36 mg·kg^(-1)·d^(-1)),respectively.Each group was given a corresponding intervention once a day for 3 d.The MIRI model was established 30 min after the last administration in all groups except the Sham group.The pathological changes of myocardial tissue were observed by Hematoxylin-eosin(HE)staining.TdT-mediated-dUTP nick end labeling(TUNEL)was used to observe the apoptosis of cardiomyocyte,the genes and proteins expression of Cx43 and endoplasmic reticulum stress related factors such as GRP78,Caspase12,CHOP and so on were detected by quantitative real-time polymerase chain reaction(q-PCR)and western blot analysis.Results Compared with the MIRI group,the degree of tissue and cell injury in each Sal group was alleviated,with a decreased apoptosis rate observed in the Sal-H group(P<0.05),the gene expression of Cx43 was up-regulated while GRP78,Caspase12,and CHOP gene expressions were down-regulated in both does groups of Sal.The protein expressions of Cx43 and GRP78 were also be up-regulated and down-regulated respectively in both dose groups of Sal,meanwhile the protein expressions of CHOP,Bax,Caspase12 and cleaved-Caspase3 were down-regulated and the protein expression of Bcl-2 was up-regulated in SAL-H group(P<0.05).Conclusion The protective effect of salidroside on cardiomyocytes may be related to the inhibition of endoplasmic reticulum stress-induced apoptosis and the imbalance of Cx43 metabolism.

关 键 词：红景天苷 缺血-再灌注 内质网应激 细胞凋亡 缝隙连接蛋白 

分 类 号：R286[医药卫生—中药学] R965[医药卫生—中医学]