老鹳草素对大鼠心肌缺血再灌注损伤的作用及其机制  

Effect and mechanism of geraniin on myocardial ischemia-reperfusion injury

作　　者：彭彩亮[1] 崔璇 蒋宁[1] 马熙凯 郭梦雨 王超龙 陈曦 王首舜 PENG Cailiang;CUI Xuan;JIANG Ning;MA Xikai;GUO Mengyu;WANG Chaolong;CHEN Xi;WANG Shoushun(Heilongjiang University of Chinese Medicine,Harbin 150040,China;Graduate School of Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学,哈尔滨150040 [2]黑龙江中医药大学研究生院,哈尔滨150040

出　　处：《吉林中医药》2023年第9期1063-1067,共5页Jilin Journal of Chinese Medicine

基　　金：黑龙江中医药大学科研基金项目(2019MS03);黑龙江省自然基金面上项目(H2017065);黑龙江省中医药管理局课题(ZYW2022-088)。

摘　　要：目的探讨老鹳草素对心肌缺血再灌注损伤的作用及其机制。方法将75只SPF级雄性小鼠用随机数字表分为老鹳草素低剂量组(5μmol/L)、中剂量组(10μmol/L)、高剂量组(20μmol/L)、假手术组和模型组,各15只。观察小鼠心脏功能,检测心肌损伤标志物,观察各组大鼠心肌组织病理变化,检测心肌组织中核转录因子E2相关因子(nuclear transcriPtion factor E2-related factor,Nrf2)信号通路相关蛋白水平。体外培养H9C2细胞,检测H9C2细胞中自噬相关蛋白及Nrf2信号通路相关蛋白水平。结果与假手术组相比,模型组心功能指标均下降;与模型组相比,老鹳草素低、中、高剂量组LVEF、FS、LVWT、HR、LVSP水平均升高(P<0.05);模型组肌红蛋白(myoglobin,Mb)、肌酸激酶同工酶(creatine kinase isoenzyme,CK-Mb)、肌钙蛋白I(cardiac tro Ponin I,c Tn I)水平高于假手术组(P<0.05);与假手术组相比,模型组LC3-II/LC3-I比值、Beclin-1升高,P62、Nrf2、游离血红素加氧酶-1(heme oxygenase-1,HO-1)蛋白水平降低(P<0.05);与模型组相比,老鹳草素低、中、高剂量组P62、Nrf2、HO-1蛋白水平升高(P<0.05);与对照组相比,H9C2细胞模拟缺血/再灌注(SI/R)损伤后LC3-II/LC3-I比值、Beclin-1升高,P62、Nrf2、HO-1蛋白水平降低(P<0.05)。结论老鹳草素可能通过激活Nrf2信号通路,抑制心肌细胞过度自噬,对心肌缺血再灌注损伤起到明显保护作用。Objective To investigate the effect and mechanism of geraniin on myocardial ischemia-reperfusion injury.Methods A total of 75 male SPF mice were randomly divided into a low-dose geraniin group(5μmol/L),a medium-dose geraniin group(10μmol/L),a high-dose geraniin group(20μmol/L),a sham operation group and a model group,with 15 rats each group.The cardiac function of mice was observed,the myocardial injury markers were detected,the pathological changes of myocardial tissue were observed in rats in each group,and the protein level of nuclear transcription factor E2-related factor(Nrf2)signaling pathway in myocardial tissue was detected.H9C2 cells were cultured in vitro,and the levels of autophagy-related proteins and Nrf2 signaling pathway-related proteins in H9C2 cells were detected.Results Compared with the sham operation group,the cardiac function indexes of the model group were all decreased;compared with the model group,the levels of LVEF,FS,LVWT,HR and LVSP in the low-,medium-,and high-dose geraniin groups were all increased(P<0.05),the levels of myoglobin(Mb),creatine kinase isoenzyme(CK-Mb),and cardiac troponin I(cTnI)in the model group were higher than those in the sham operation group(P<0.05).Compared with the sham operation group,the ratio of LC3-II/LC3-I and Beclin-1 in the model group were increased,while the protein levels of P62,Nrf2,and free heme oxygenase-1(HO-1)were decreased(P<0.05).Compared with the model group,the protein levels of P62,Nrf2 and HO-1 in the low-,medium-,and high-dose geraniin groups were increased(P<0.05).Compared with the control group,the ratio of LC3-II/LC3-I and Beclin-1 were increased after simulated ischemia/reperfusion(SI/R)injury,while the protein levels of P62,Nrf2 and HO-1 were decreased(P<0.05).Conclusion Geraniin may inhibit the excessive autophagy of cardiomyocytes by activating the Nrf2 signaling pathway,and play a significant protective role in myocardial ischemia-reperfusion injury.

关 键 词：老鹳草素 心肌缺血/再灌注损伤 自噬 Nrf2信号通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]