摘要
目的研究柴胡三参胶囊对新生大鼠心肌细胞损伤和小鼠心力衰竭模型中磷脂酰肌醇3激酶(phosphoinositide3-kinase,PI3K)/Akt和丝裂原激活的蛋白激酶(mitogen-activated protein kinase,MAPK)通路相关蛋白表达的影响,探讨其拮抗阿霉素诱导的心脏毒性的作用机制。方法用阿霉素诱导生成新生大鼠心肌细胞(neonatal rat ventricular myocyte,NRVM)损伤模型和小鼠心力衰竭模型,随机分为对照(no treatment,NT)组、模型(Model)组、柴胡三参胶囊预处理(CHSSC)组。末次给药后次日处死小鼠,处死前进行超声心动图检测,采用CCK-8法检测细胞活力,TUNEL法检测细胞凋亡,试剂盒检测血清肌酸激酶(CK)、乳酸脱氢酶(LDH)、丙二醛(MDA)含量,Western blot法检测裂解的半胱氨酸天冬氨酸蛋白酶-3(c-Caspase 3)和磷酸化丝裂原激活的蛋白激酶(p-p38MAPK)、磷酸化磷脂酰肌醇3激酶(p-PI3K)、磷酸化蛋白激酶(p-Akt)蛋白表达情况。结果与NT组比较,Model组以阿霉素剂量依赖性方式降低NRVM细胞活力,诱发细胞凋亡(P<0.01);氧化应激指标CK、LDH、MDA明显增加(P<0.01);左室EF值下降(P<0.01),LVIDS、LVIDd、LVESV、LVEDV水平增加(P<0.05);p-p38MAPK、c-Caspase 3和p-PI3K蛋白表达水平升高(P<0.01)。与Model组比较,CHSSC组增加细胞活力、减轻细胞凋亡,差异有明显统计学意义(P<0.01);氧化应激指标CK、LDH、MDA降低(P<0.01);EF增加(P<0.05),LVIDS、LVIDd、LVESV、LVEDV下降(P<0.05);p-p38MAPK、c-Caspase 3和p-PI3K蛋白表达水平降低(P<0.01)。结论柴胡三参胶囊可改善阿霉素诱导的心脏毒性,可能与其通过调控PI3K/Akt和p38MAPK通路抑制氧化应激和细胞凋亡相关。
Objective To investigate the effects of Chaihu Sanshen Capsule on the expression of proteins related to phosph-oinositide 3-kinase(PI3K)/Akt kinase and mitogen-activated protein kinase(MAPK)pathways in neonatal rat cardiomyocyte injury model and mouse heart failure model,and to explore the mechanism in antagonizing adriamycin-induced cardiotoxicity.Methods A neonatal rat ventricular myocyte(NRVM)injury model and a mouse heart failure model were induced by adriamycin,which were divided into no treatment(NT)group,model group,and Chaihu Sanshen Capsule pretreatment(CHSSC)group.Mice were sacrificed the next day after the last administration,and echocardiography was detected before sacrifice.CCK-8 method was used to detect cell viability;TUNEL was used to detect cell apoptosis;the kit was used to detect serum creatine kinase(CK),lactate dehydrogenase(LDH),and malondialdehyde(MDA)levels.The protein expression of cleaved c-Caspase 3(c-Caspase 3),phosphorylated mitogen-activated protein kinase(p-p38MAPK),p-PI3K and phosphorylated protein kinase(p-Akt)were evaluated by Western blot.Results Compared with the NT group,the NRVM cell viability reduced and apoptosis was induced in the model group due to the adriamycin dose-dependent manner(P<0.01);the levels of oxidative stress indexes CK,LDH and MDA increased significantly(P<0.01);the left ventricular EF decreased(P<0.01),while LVIDS,LVIDd,LVESV and LVEDV increased(P<0.05);the expression levels of p-p38MAPK,c-Caspase 3 and p-PI3K were significantly higher(P<0.01).Compared with the model group,cell viability increased and the apotosis reduced in CHSSC group(P<0.01);the levels of oxidative stress indexes CK,LDH and MDA decreased significantly(P<0.01);EF increased(P<0.05);LVIDS,LVIDd,LVESV and LVEDV decreased(P<0.01);the expression levels of p-p38MAPK,c-Caspase 3 and p-PI3K were significantly decreased(P<0.01).Conclusion Chaihu Sanshen Capsule can ameliorate adriamycin-induced cardiotoxicity,and the mechanism may be related to the inhibition of oxidative stress and apoptosis by
作者
谭彩
曹蛟
张杼惠
刘建和
TAN Cai;CAO Jiao;ZHANG Zhuhui;LIU Jianhe(The First Hospital of Hunan University of Chinese Medicine,Changsha,Hunan 410007,China;Hunan University of Chinese Medicine,Changsha,Hunan 410208,China)
出处
《湖南中医药大学学报》
CAS
2022年第9期1434-1441,共8页
Journal of Hunan University of Chinese Medicine
基金
湖南省中医药管理局项目(2021011)
湖南省省级财政中医药项目(rsk-010-05006-01)
湖南省科学技术厅临床医疗技术创新引导项目(2020SK51405)。
