川芎嗪预处理对缺血再灌注心肌线粒体功能的保护作用研究  

Protective effect of ligustrazine preconditioning on myocardial mitochondrial function during ischemia and reperfusion

作　　者：朱可夫[1] 吴少泽 娄江杰 李琳[2] 翁莹政 唐礼江[1] Zhu Kefu;Wu Shaoze;Lou Jiangjie;Li Lin;Weng Yingzheng;Tang Lijiang(Department of Cardiology,Zhejiang Hospital,Hangzhou 310013,China;Department of Rehabilitation Medicine,Zhejiang Hospital,Hangzhou 310013,China)

机构地区：[1]浙江医院心血管内科,杭州310013 [2]浙江医院康复医学科,杭州310013

出　　处：《心脑血管病防治》2022年第1期34-38,共5页CARDIO-CEREBROVASCULAR DISEASE PREVENTION AND TREATMENT

基　　金：浙江省中医药科技计划项目(2018ZQ004);浙江省基础公益研究计划项目(LGF20H170008);浙江省医药卫生科技计划项目(2021KY426)。

摘　　要：目的探讨川芎嗪预处理对大鼠心肌缺血再灌注损伤(IRI)的保护作用机制。方法40只Sprague-Dawley(SD)大鼠,随机分为假手术组、缺血再灌注组、川芎嗪组和川芎嗪+氯尼达明组。除假手术组外其余三组均建立在体SD大鼠心肌IRI模型,川芎嗪(10 mg/kg)于缺血前5 min静脉注射,线粒体渗透性转换孔道(mPTP)抑制剂氯尼达明(50 mg/kg)于松开结扎线前10 min经腹腔注射。比较各组间心肌梗死面积、心肌损伤标志物、心肌氧化损伤指标以及心肌线粒体解耦联蛋白3(UCP3)的转录和蛋白表达水平。结果与缺血再灌注组相比,川芎嗪组和川芎嗪+氯尼达明组的心肌梗死面积、血浆肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)、乳酸脱氢酶(LDH)、心肌组织丙二醛(MDA)水平显著降低(均P<0.05),UCP3 mRNA和蛋白表达水平、心肌组织超氧化物歧化酶(SOD)、三磷酸腺苷(ATP)水平显著升高(均P<0.05);与川芎嗪组相比,川芎嗪+氯尼达明组的心肌梗死面积、血浆CK、CKMB、LDH水平、心肌组织MDA水平显著升高,ATP水平显著降低(均P<0.05),而两组间UCP3的表达水平无统计学意义(均P>0.05)。结论川芎嗪预处理能减少心肌梗死面积,有效减轻心肌IRI,其机制可能与抗氧化、维持线粒体能量代谢和UCP3相关的信号通路作用有关。Objectives To investigate the mechanism of protective effect of ligustrazine pretreatment on myocardial ischemia reperfusion injury(IRI)in rats.Methods 40 Sprague-Dawley(SD)rats were randomly divided into Sham group,IRI group,ligustrazine group,and ligustrazine plus lonidamine group.In addition to the Sham group,the other three groups were established in the myocardial IRI model of in vivo SD rats.Ligustrazine(10 mg/kg)was injected intravenously 5min before ischemia,and lonidamine(50 mg/kg),an inhibitor of mitochondrial permeability transformation pathway(mPTP),was injected intraperitoneally 10min before the ligation line was released.Myocardial infarction area,myocardial damage markers,myocardial oxidative damage indicators,and uncoupling protein 3(UCP3)transcription and protein expression levels were compared between the groups.Results Compared with IRI group,myocardial infarction area,plasma creatine kinase(CK),creatine kinase isoenzyme(CK-MB),cardiac troponin I(cTnI),lactate dehydrogenase(LDH)levels and myocardial tissue malondialdehyde(MDA)were significantly reduced in ligustrazine group and ligustrazine plus lonidamine group(P<0.05),mRNA and protein expression of UCP3 and myocardial tissue superoxide dismutase(SOD),adenosine triphosphate(ATP)were significantly increased in ligustrazine group and ligustrazine plus lonidamine group(P<0.05);Compared with the ligustrazine group,the myocardial infarction area,plasma CK,CK-MB,LDH levels and myocardial MDA level in the ligustrazine plus lonidamine group were significantly increased and ATP levels was significantly decreased(all P<0.05),while UCP3 expression was not significantly different between the two groups(all P>0.05).Conclusion Ligustrazine preconditioning can reduce myocardial infarction area and effectively reduce myocardial IRI,and its mechanism may be related to antioxidation,maintenance of mitochondrial energy metabolism and UCP3-related signaling pathways.

关 键 词：川芎嗪 心肌缺血/再灌注 解耦联蛋白3 线粒体能量代谢 

分 类 号：R285.5[医药卫生—中药学]