摘要
目的观察鹿红方对心肌梗死大鼠心功能障碍的影响,并探讨其作用机制。方法60只大鼠随机分为假手术组、模型组、鹿红方组、氯喹组、鹿红方+氯喹组。药物干预2周后,采用超声检测大鼠的心脏功能与结构,HE、Masson染色观察心肌组织的病理改变,ELISA检测血清LDH、CK-MB活性,透射电镜观察心肌组织的超微结构,Western blot、免疫组化检测心肌组织中自噬蛋白的表达。结果与假手术组比较,模型组大鼠心功能水平降低,心肌纤维化面积增大,血清LDH、CK-MB活性升高,心肌组织结构损伤及自噬空泡形成增多,LAMP2蛋白表达降低,Beclin1、LC3-Ⅱ、P62蛋白表达升高;鹿红方干预后,心肌梗死大鼠心功能改善,心肌纤维化面积缩小,血清LDH、CK-MB活性降低,心肌组织结构损伤减轻,心肌组织中自噬溶酶体的数量增加,Beclin1、LAMP2、LC3-Ⅱ蛋白表达升高,P62蛋白表达降低,促进心肌梗死后受损心肌的自噬流,但这些作用均可被氯喹所消除。结论鹿红方可通过调节Beclin1/LAMP2介导的途径,提高自噬小体的形成和促进自噬流的通畅来减轻心肌梗死后的心脏功能障碍,发挥心脏保护作用。
AIM To observe the effects of Luhong Formula on rats with post-myocardial infarction cardiac dysfunction,and to explore its mechanism.METHODS Sixty rats were randomly divided into sham operation group,model group,Luhong Formula group,chloroquine group and Luhong Formula+chloroquine group.Rats treated with two weeks of drug had their cardiac function and structure measured by ultrasound;their myocardial pathological changes observed by HE and Masson staining;their serum activities of LDH and CK-MB detected by ELISA;their myocardial ultrastructures observed by transmission electron microscopy;and the myocardial autophagy protein expressions detected by Western blot and immunohistochemistry.RESULTS Compared with the sham operation group,the model group displayed decreased cardiac function levels,enlarged area of myocardial fibrosis,more serum activities of LDH and CK-MB,increased myocardial tissue structural damage and autophagy vacuoles,down-regulated LAMP2 expression,and up-regulated expressions of Beclin1,LC3-II,and P62.To rat victims of myocardial infarction,the treatment of Luhong Formula brought forth improved cardiac function,reduced area of myocardial fibrosis,compromised activities of serum LDH and CK-MB,and relieved damage in myocardial structure,increased the number of autolysosomes in myocardial tissue,up-regulated the expressions of Beclin1,LAMP2 and LC3-II,and down-regulated the expression of P62 to promote the autophagy flux in the myocardium damaged by myocardial infarction.However,all these effect could be eliminated by chloroquine.CONCLUSION Being a cardioprotector,Luhong Formula alleviates post-myocardial infarction cardiac dysfunction through improvement of autophagosomes formation and autophagic flux via Beclin1/LAMP2 pathway.
作者
赵丹丹
瞿惠燕
杨涛
张晓青
周华
ZHAO Dan-dan;QU Hui-yan;YANG Tao;ZHANG Xiao-qing;ZHOU Hua*(Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)
出处
《中成药》
CAS
CSCD
北大核心
2022年第5期1427-1434,共8页
Chinese Traditional Patent Medicine
基金
国家自然科学基金资助项目(81673753,81973656)
上海市科学技术委员会科技支撑项目(18401932800)
上海市申康医学发展中心三年行动计划(SHDC2020CR1053B)。
关键词
鹿红方
心肌梗死
自噬流
心功能障碍
Luhong Formula
myocardial infarction
autophagy flux
cardiac dysfunction
