摘要
目的探讨川芎嗪(TMP)对冠心病大鼠心肌损伤的影响及其可能的作用机制。方法选取50只雄性大鼠用高脂饮食联合后腔注射垂体后叶素法建立冠心病(CHD)大鼠模型,48只造模成功大鼠随机分为模型组、TMP低剂量、高剂量组和西药组,各12只,其余为对照组(15只)。TMP低剂量、高剂量组灌胃给药100、150 mg·kg^(-1)TMP混悬液(生理盐水配制),西药组静脉注射1 mg·kg^(-1)盐酸地尔硫注射液,连续4周,对照组及模型组给予等量生理盐水。ELISA法检测大鼠血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1(IL-1β)和白细胞介素-6(IL-6)水平;测定血清肌红蛋白(MB)、肌酸激酶(CK)和肌酸激酶同工酶-MB(CK-MB)水平;检测大鼠心肌组织匀浆中丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)和超氧化物岐化酶(SOD)水平;HE染色观察心肌组织病理学变化;RT-PCR和Western blot检测大鼠心肌组织腺苷酸活化蛋白激酶(AMPK)及其磷酸化蛋白、核因子E2相关因子2(Nrf-2)、血红素加氧酶1(HO-1)mRNA和蛋白表达情况。结果大鼠血清TNF-α、IL-1β、IL-6、Mb、CK、CK-MB、MDA水平,TMP低剂量、高剂量组和西药组比模型组低,TMP高剂量组和西药组比TMP低剂量组低(P<0.05);GSH-Px、SOD、p-AMPK蛋白表达、Nrf-2和HO-1 mRNA和蛋白表达水平,TMP低、高剂量组和西药组比模型组高(P<0.05)。TMP高剂量组各项指标与西药组的差异无统计学意义。结论TMP可减轻CHD大鼠炎性反应和氧化应激反应,在一定程度上改善心肌损伤,可能与激活AMPK/Nrf-2/HO-1信号通路有关。
Objective To investigate the effect and mechanism of tetramethylpyrazine(TMP)on myocardial injury in rats with coronary heart disease.Methods 50 male rats were randomly selected to establish coronary heart disease(CHD)model by high-fat diet combined with posterior cavity injection of pituitrin.48 successful modeled rats were randomly divided into model group,TMP low and high dose group and western medicine group,with 12 rats in each group,and 15 rats without modeling were taken as the control group.TMP low and high dose groups were given 100 and 150 mg·kg^(-1) TMP suspension(prepared with normal saline)by gavage for 4 weeks.The western medicine group was given 1 mg·kg^(-1) diltiazern hydrochloride injection.The control group and model group were given the same amount of normal saline.The levels of serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)were detected by ELISA.The levels of serum myoglobin(MB),creatine kinase(CK),creatine kinase isoenzyme(CK-MB)in each group were also detected.The levels of malondialdehyde(MDA),glutathione peroxidase(GSH-Px)and superoxide dismutase(SOD)in rat myocardial tissue homogenate were measured.Myocardial histopathological changes were observed by HE staining.The expression of adenylate activated protein kinase(AMPK)and its phosphorylated protein,nuclear factor E2 related factor 2(Nrf-2),heme oxygenase 1(HO-1)mRNA and protein were detected by RT-PCR and Western blot.Results The serum levels of TNF-α,IL-1β,IL-6,MB,CK,CK-MB and MDA in TMP low and high dose group and western medicine group were lower than those in model group,and those in TMP high dose group and western medicine group were lower than those in TMP low dose group(P<0.05).The levels of GSH-Px,SOD,p-AMPK protein expression,Nrf-2 and HO-1 mRNA and protein expression in TMP low and high-dose group and western medicine group were higher than those in model group(P<0.05).There was no significant difference between TMP high dose group and western medicine group.Conclusion TMP can reduce inflammatory response and oxidative stress response in CHD rats and improve myocardial injury to a certain degree,which may be related to the activation of AMPK/Nrf-2/HO-1 signal pathway.
作者
刘英
程敏菊
魏鹏辉
LIU Ying;CHENG Minju;WEI Penghui(Department of Cardiology,Kailuan General Hospital,Tangshan 063000,China;Department of Cardiology,Xingtai People's Hospital,Xingtai 054000,China;Department of Cardiology,Fengfeng General Hospital of North China Medical Group,Handan 056000,China)
出处
《西北药学杂志》
CAS
2023年第3期62-67,共6页
Northwest Pharmaceutical Journal
基金
2021年河北省医学科学研究课题计划项目(编号:20211608)。
关键词
川芎嗪
冠心病
心肌损伤
腺苷酸活化蛋白激酶
核因子E2相关因子2
血红素加氧酶1
tetramethylpyrazine
coronary heart disease
myocardial injury
adenylate activated protein kinase
nuclear factor E2 and related factor 2
heme oxygenase 1
