摘要
目的:探究当归补血汤对使用阿霉素小鼠心肌损伤的保护作用及其通过PI3K介导通路对心肌细胞自噬的影响。方法:取40只雄性ICR小鼠随机分为对照组、阿霉素组(ADR组)、阿霉素+巴佛洛霉素A1组(ADR+Baf组)、当归补血汤干预阿霉素+巴佛洛霉素A1组(DBD+Baf组)、当归补血汤干预阿霉素组(DBD组),每组8只,予相应药物,实验周期28d,记录小鼠一般状况、体质量变化,测量心功能、血清学指标、心肌组织形态学改变及自噬相关蛋白LC3B、PI3K水平变化。结果:与对照组比较,ADR两组活动能力弱,体质量显著降低(P<0.01),心肌组织细胞排列紊乱,细胞内出现水肿、空泡变性,左室射血分数(EF%)、短轴缩短率(FS%)、左室后壁舒张末厚度(LVPWd)、左室后壁收缩末厚度(LVPWs)均降低,左室舒张末内径(LVIDd)、左室收缩末内径(LVIDs)增高,血清乳酸脱氢酶(LDH)、肌酸激酶同工酶-MB(CK-MB)升高(P<0.05,P<0.01),LC3B-Ⅱ/LC3B-Ⅰ升高,PI3K蛋白水平降低(P<0.01)。与ADR两组比较,DBD两组一般状况改善,体质量提高(P<0.05),心肌组织细胞病理改变较轻,EF%、FS%升高,LVIDs降低,CK-MB降低(P<0.05,P<0.01)。ADR组与DBD组、ADR+Baf组与DBD+Baf组比较,LC3B-Ⅱ/LC3B-Ⅰ均降低,PI3K蛋白水平均升高(P<0.05)。结论:当归补血汤对使用阿霉素小鼠心肌损伤有保护作用,其机制可能与激活PI3K介导通路,抑制心肌细胞自噬有关。
Objective:To explore the protective effect of Danggui Buxue Decoction on myocardial injury in mice treated with adriamycin and its effect on myocardial cell autophagy through phosphoinosmde-3-kinase(PI3 K)-mediated pathway.Methods:Forty male ICR mice were randomly divided into control group,adriamycin group(ADR group),adriamycin+bafilomycin A1 group(ADR+Baf group),and Danggui Buxue Decoction intervention Adriamycin+Bafilomycin A1 group(DBD+Baf group),Danggui Buxue Decoction intervention adriamycin group(DBD group),each group was given the corresponding drugs with 8 mice,the experimental period was 28 d,and the general conditions and changes in body weight of the mice were recorded.Cardiac function,serological indicators,myocardial tissue morphology and autophagy-related protein microtubules associated protein 1 light chain 3-B(LC3 B),PI3 K level changes were measured.Results:Compared with the control group,the ADR two groups had weak activity ability,significantly reduced body weight(P<0.01),disordered arrangement of myocardial tissue cells,intracellular edema,vacuolar degeneration,and left ventricular ejection fraction(EF%),fractional shortening(FS%),left ventricular posterior wall end-diastolic(LVPWd),left ventricular posterior wall end-systolic(LVPWs)were all reduced,left ventricular internal diastolic end-diastolic(LVIDd),left ventricular internal diastolic end-systolic(LVIDs)increased,serum lactate dehydrogenase(LDH)and creatine kinase isoenzyme-MB(CK-MB)increased(P<0.05,P<0.01),LC3 B-Ⅱ/LC3 B-Ⅰincreased,and PI3 K protein level decreased(P<0.01).Compared with the ADR group,the general condition of the DBD group was improved,the body mass increased(P<0.05),the pathological changes of myocardial tissue cells were reduced,EF%,FS%increased,LVIDs decreased,and CK-MB decreased(P<0.05,P<0.01).Compared with the DBD group,the ADR+Baf group and the DBD+Baf group,the LC3 B-Ⅱ/LC3 B-Ⅰin the ADR group were all decreased,and the PI3 K protein level in the ADR group was increased(P<0.05).Conclusion:Danggui Buxue Decoction has a protective effect on myocardial injury in mice treated with adriamycin.The mechanism may be related to the activation of PI3 K-mediated pathways and inhibition of cardiomyocyte autophagy.
作者
毛启远
刘兰椿
王瑾琨
曹康迪
张雨薇
高鹏荣
杨晓敏
王勇
MAO Qi-yuan;LIU Lan-chun;WANG Jin-kun;CAO Kang-di;ZHANG Yu-wei;GAO Peng-rong;YANG Xiao-min;WANG Yong(Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2021年第5期2515-2520,共6页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金项目(No.81673712)。
关键词
当归补血汤
阿霉素心肌损伤
细胞自噬
药效学
PI3K介导通路
Danggui Buxue Decoction
Adriamycin myocardial injury
Autophagy
Pharmacodynamics
PI3K mediated pathway