当归补血汤对阿霉素心肌损伤小鼠的保护作用及对心肌细胞自噬的影响

Protective effect of Danggui Buxue Decoction on myocardial injury induced by adriamycin in mice and its effect on autophagy of cardiomyocytes

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.