丹七片调控神经酰胺通路改善心肌梗死后心力衰竭小鼠的药效及机制研究  

Effect and Mechanism of Danqi Pill on Regulating Ceramide Pathway in Improving Heart Failure after Myocardial Infarction in Mice

作　　者：田雪 陈旭 张亚雯 姜茜茜 江艳艳 孙乾斌 刘恬恬 邵明燕 马林 王勇 TIAN Xue;CHEN Xu;ZHANG Yawen;JIANG Qianqian;JIANG Yanyan;SUN Qianbin;LIU Tiantian;SHAO Mingyan;MA Lin;WANG Yong(School of Life Sciences,Beijing University of Chinese Medicine,Beijing 10029,China)

机构地区：[1]北京中医药大学生命科学学院,北京100029 [2]北京中医药大学中医学院,北京100029 [3]证候与方剂基础研究教育部重点实验室,北京100029 [4]证候与方剂基础研究北京市重点实验室,北京100029

出　　处：《中西医结合心脑血管病杂志》2022年第19期3547-3553,共7页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金项目(No.81822049)。

摘　　要：目的探究丹七片(DQP)基于神经酰胺通路抗心肌脂毒性的药效及机制研究。方法利用冠状动脉左前降支结扎术制备心肌梗死后心力衰竭动物模型,分为假手术组、模型组、丹七片组、辛伐他汀组。利用超声、血生化、病理切片染色、蛋白免疫印迹法(Western Blot)和酶联免疫吸附(ELISA)法等技术进行相应指标的检测。结果与模型组比较,丹七片组左心室射血分数(LVEF)和左心室短轴缩短率(LVFS)升高(P<0.01或P<0.001),而左室收缩末期内径(LVESD)和左室舒张末期内径(LVEDD)降低(P<0.05或P<0.01)。苏木精-伊红(HE)和Masson染色显示,丹七片能够减轻小鼠心肌损伤的程度,改善病理结构变化。血清检测结果提示丹七片可以有效降低心肌损伤标志物肌酸激酶同工酶(P<0.05)、肌钙蛋白I(P<0.001)的表达,进而减轻心脏损伤程度。此外,丹七片干预后可明显下调单链丝氨酸棕榈酰转移酶长链1(SPTLC1)及SPT长链2(SPTLC2)蛋白的表达(P<0.05或P<0.01),并明显降低心肌组织内神经酰胺含量(P<0.001)。结论丹七片可能通过调控从头合成途径关键限速酶单链丝氨酸棕榈酰转移酶来降低心力衰竭小鼠心肌神经酰胺水平,从而改善小鼠心功能,减轻心肌损伤。Objective To explore the efficacy and mechanism of Danqi pill(DQP)against myocardial lipotoxicity based on ceramide pathway.Methods Animal models of heart failure after myocardial infarction(MI)were prepared by ligation of the left anterior descending coronary artery.The mice were divided into sham group,model group,DQP group,and Simvastatin(2.9 mg/kg)group.The corresponding indexes were detected by echocardiography,blood biochemistry,pathological section staining,Western Blot,and enzyme-linked immunosorbent assay(ELISA),respectively.Results Compared with the model group,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)in the DQP group were significantly increased(P<0.01 or P<0.001),and left ventricular end-systole diameter(LVESD)and left ventricular end-diastole diameter(LVEDD)were decreased(P<0.05 or P<0.01).HE and Masson staining showed that DQP reduced the degree of myocardial injury and improve the pathological structure of mice.The results of serum test indicated that DQP effectively reduced the expression of myocardial injury markers such as CK-MB(P<0.05)and cTnI(P<0.001),and then reduced the degree of cardiac injury.In addition,DQP significantly down-regulated serine-palmitoyl transferase long chain 1(SPTLC1)and serine-palmitoyl transferase long chain 2(SPTLC2)protein expression(P<0.05 or P<0.01),and significantly decreased the content of ceramide in myocardial tissue(P<0.001).Conclusion DQP may reduce the level of ceramide in heart failure mice by regulating serine palmitoyltransferase(SPT),which is a key rate-limiting enzyme in de novo synthesis pathway,thereby improving cardiac function and alleviating myocardial injury.

关 键 词：心肌梗死 心力衰竭 丹七片 单链丝氨酸棕榈酰转移酶 神经酰胺 鞘脂 

分 类 号：R285.5[医药卫生—中药学]