川穹嗪对阿霉素诱导的急性心衰小鼠心肌损伤和凋亡的保护作用  

Protect effects of tetramethylprazine on cardiomyocytes apoptosis and injury in adriamycin-induced acute heart failure mice

作　　者：张伟民[1,2] 李瑞芳[1] 付银峰[1] 姬广全[1] 周洁[1] 刘鹤阳 王建刚[1] 陈豪[1] 

机构地区：[1]河南科技大学医学院药理河南科技大学第一附属医院药剂科,河南洛阳471003 [2]河南科技大学医学院药理学与分子生物学重点实验室,河南洛阳471003

出　　处：《中国临床药理学杂志》2014年第8期708-711,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究川穹嗪(TMP)对阿霉素诱导的急性心衰(AHF)小鼠心肌损伤和凋亡的保护作用及机制。方法动物分为对照组(10 mL·kg-1·d-10.9%NaCl)、模型组(阿霉素20 mg·kg-1·d-1,连续2次)、依那普利组(10mg·kg-1·d-1)和高、中、低3个剂量(60,30,15 mg·kg-1·d-1)TMP组,连续给药2周后,阿霉素诱导建立AHF模型,检测心肌酶谷草转氨酶(AST)、肌酸激酶(CK)及肌酸激酶同工酶(CK-MB)水平的变化。苏木精-伊红(HE)染色进行病理学检查,Western-Blot检测心肌Bax和Bcl-2的表达变化。结果模型组血清心肌酶的水平升高,心肌受损并且有炎症浸润,TMP组和依那普利组的心肌酶的水平显著降低,心肌损伤及炎症得到明显改善。TMP和依那普利可以降低AHF小鼠心肌bax表达而增加Bcl-2的表达。结论 TMP对阿霉素诱导的AHF小鼠心肌具有保护作用,其机制可能与TMP防止心肌细胞损伤和凋亡有关。Objective To investigate the protective effect of tetramethyl-prazine （ TMP ） on adriamycin （ ADR ） -induced acute heart failure （ AHF） and underlying molecular mechanisms.Methods Male Kun-ming mice were randomly divided into six groups： control group （0.9%NaCl 10 mL· kg -1· d-1）, model group （ADR 20 mg· kg -1, continuous twice ） , enalapril group （ 10 mg · kg -1 · d-1 ） and TMP high, middle and low dose groups （60, 30, 15 mg· kg-1 · d -1 ）.All groups were administered drugs for 2 weeks, then ADR 20 mg· kg -1 was given intraperitoneally twice to establish AHF model.Cardiac enzymes including aspartate aminotransferase （AST）, creatine kinase （CK） and MB isoenzyme of creatine kinase （ CK-MB） were detected.Histopatho-logical examination was performed by hematoxylin -eosin （ HE ） stai-ning.Western-blot analysis was used to investigate the expression levels of Bax and Bcl-2.Results AST, CK and CK-MB of left ventricle of AHF mice showed a significant increase while TMP treatment decreased their levels in myocardial tissue.Myocardial tissue of AHF mice was damaged and myocardial fiber arranged disorderly.Myocardial cells showed vacuolar degeneration and necrosis in AHF mice.Administration of TMP obviously attenuated myocardial damage and myocardial fiberdisordered arrangement.Further studies revealed that TMP decreased the expression of pro -apoptotic factor of Bax and pro-inflammatory cytokine TNF-αwhile increased the expression of anti -apoptotic factor of Bcl-2.Conclusion TMP exerts protective effect on adriamycin -induced AHF partially by inhibition of cardiomyocytes apoptosis and cardi-ac enzymes levels .

关 键 词：急性心衰 阿霉素 川穹嗪 心肌酶 凋亡 

分 类 号：R965.1[医药卫生—药理学] R977.9[医药卫生—药学]