摘要
目的:探究心舒宝片对心肌梗死(MI)后小鼠心功能的保护作用及其对凝溶胶蛋白(GSN)的影响。方法:结扎左冠状动脉前降支建立MI模型。C57BL/6J雄性小鼠随机分为假手术组,模型组,心舒宝片高、低剂量组和卡托普利组,每组10只。心舒宝片低、高剂量组分别灌胃0.26、0.52 g·kg^(-1)·d^(-1)心舒宝片混悬液,卡托普利组灌胃4.875 mg·kg^(-1)·d^(-1)卡托普利片混悬液,假手术组和模型组灌胃等体积双蒸水,连续灌胃4周,采用超声多普勒检测检测小鼠的心脏功能,单细胞测序技术解析MI影响的关键细胞类型和基因,Western Blot检测心肌组织中关键蛋白GSN的表达情况。结果:与模型组比较,心舒宝片高剂量组小鼠心脏指数显著减少(P<0.05);射血分数(LVEF)显著增加(P<0.05),模型组心肌细胞主要富集到Ryr2、Myh6、Atp2a2、Actc1、Myl3和Tnnt2等,成纤维细胞富集到GSN、COL1a1和COL3a1,内皮细胞富集到PECAM1、EGFL7和VEGFA,KEGG涉及到心肌收缩、肥厚型心肌病、扩张型心肌病等;心舒宝片高剂量组GSN表达显著减少(P<0.05)。结论:心舒宝片能减少MI小鼠心肌组织的GSN蛋白表达,减轻心脏纤维化,进而逆转左心室重构并改善左心室功能,提高MI小鼠的生活质量。
Objective:To explore the protective effect of Xinshubao Tablets on cardiac function in mice after myocardial infarction(MI)and its influence on gelsolin(GSN).Methods:MI model was established by ligating LAD in mice.The C57BL/6J male rats were divided into sham group,model group,low dose of Xinshubao Tablets(XSB-L)group,high dose of Xinshubao Tablets(XSB-H)group,and Captopril(CAP)group,5 in each group.XSB-L group was given Xinshubao Tablets suspension(0.26 g·kg^(-1)·d^(-1)),XSB-H group was given Xinshubao Tablets suspension(0.52 g·kg^(-1)·d^(-1)),CAP group was given Captopril suspension(4.875 mg·kg^(-1)·d^(-1)),sham group and model group were given double distilled water.And they were given corresponding liquid intragastric treatment for 4 weeks.The heart function of the rats was detected by ultrasound,the specific cell types and genes impacted by MI was utilized to identify by single-cell sequencing technology.The expression of GSN in myocardial tissue was detected by Western Blot.Results:Compared with the model group,the cardiac index was significantly reduced(P<0.05);LVEF increased significantly(P<0.05).Single cell sequencing of the model group analysis demonstrated the enrichment of Ryr2,Myh6,Atp2a2,Actc1,Myl3,and Tnnt2 in the myocardial cells,Fibroblasts show increased GSN,COL1a1and COL3a1,Endothelial cells show enriched PECAM1,EGFL7 and VEGFA.KEGG involved cardiac muscle contraction,hypertrophic cardiomyopathy,dilated cardiomyopathy,etc.Western Blot also showed that the expression of GSN decreased significantly in XSB_H group(P<0.05).Conclusion:The intervention of XSB can inhibit the expression of GSN protein in myocardial tissue of mice after MI,reduce fibrosis of MI tissue,reverse left ventricular remodeling,improve left ventricular function and improve the quality of life of mice after MI.
作者
张丰荣
江雪
刘妹
李贤煜
肖洪贺
杨洪军
ZHANG Fengrong;JIANG Xue;LIU Mei;LI Xianyu;XIAO Honghe;YANG Hongjun(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Experimental Research Center,China Academy of Chinese Medical Sciences,Beijing 100700,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2024年第5期2260-2265,共6页
China Journal of Traditional Chinese Medicine and Pharmacy
关键词
心舒宝片
心肌梗死
单细胞测序
凝溶胶蛋白
心脏纤维化
Xinshubao Tablets
Myocardial infarction(MI)
Single cell sequencing
Gelsolin
Cardiac fibrosis
