玉郎伞查尔酮对异丙肾上腺素诱导的小鼠心肌缺血的保护作用  

Protective effects of 17-methoxyl-7-hydroxyl-benzofuran chalcone against isoproterenol-inducing myocardial ischemia in mice

作　　者：覃斐章[1] 秦秋华 禤霏霏 黄媛恒[1] 李映新[1] 董敏 QIN Fei-Zhang;QIN Qiu-Hua;XUAN Fei-Fei(Pharmacology Department,Guangxi Medical University,Nanning 530021,Guangxi,China)

机构地区：[1]广西医科大学,广西南宁530021 [2]南宁市第二人民医院

出　　处：《中国老年学杂志》2021年第5期1054-1059,共6页Chinese Journal of Gerontology

基　　金：国家自然科学基金(81302859);广西自然科学基金(2017GXNSFAA198145,2018GXNSFAA050121)。

摘　　要：目的研究玉郎伞查尔酮(YLSC)对异丙肾上腺素所致的小鼠心肌缺血的影响及可能机制。方法60只雄性KM小鼠随机分为正常组、模型组、普萘洛尔组(1 mg/kg)、YLSC低、中、高剂量组(3,6,12 mg/kg)。各组尾静脉注射药物15 d,随后腹腔注射异丙肾上腺素(10 mg/kg)3 d建立小鼠心肌缺血模型。实验结束后,测定血清心肌肌钙蛋白(cTn)T、肌酸激酶同工酶(CK-MB)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-1β、IL-18含量。取心肌组织,苏木素-伊红(HE)染色观察小鼠心肌病理变化,并测定心肌丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)的含量;Western印迹测定心肌NOD样受体蛋白(NLRP)3、凋亡相关颗粒样蛋白(ASC)、半胱氨酸天冬氨酸蛋白酶(Caspase)-1的蛋白表达量。结果与模型组比较,YLSC可明显减轻心肌病理损伤,提高SOD、CAT、GSH-Px水平,降低MDA、cTnT、CK-MB、TNF-α、IL-6、IL-1β、IL-18水平(P<0.05,P<0.01),抑制心肌NLRP3、ASC、Caspase-1蛋白表达(P<0.05,P<0.01),并呈剂量-效应关系。结论YLSC可减轻异丙肾上腺素所致的小鼠心肌缺血损伤,机制可能与减少氧化应激,抑制TNF-α、IL-6、IL-1β、IL-18的产生和NLRP3炎症小体的表达有关。Objective To explore the effects of 17-methoxyl-7-hydroxyl-benzofuran chalcone(YLSC)on myocardial ischemia induced by isoproterenol in mice and the possible mechanisms.Methods 60 male KM mice were randomly divided into six groups:normal group,model group,isoproterenol group(1 mg/kg),YLSC low,medium and high dosage(3,6,12 mg/kg)groups.Mice were injected with corresponding drugs via the tail vein for 15 days,then 10 mg/kg isoproterenol was injected intraperitoneally into mice for three consecutive days to make the model of myocardial ischemia.After experiments,levels of cardiac troponin(cTn)T,creatine kinase(CK)-MB,tumor necrosis factor(TNF)-α,interleukin(IL)-6,IL-1βand IL-18 in serum were tested.Myocardial pathological changes in mice were observed by HE staining.The contents of malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GSH-Px)in myocardium were measured.Protein expressions of NOD-like receptor super family,pyrin domain containing(NLRP)3,adaptor protein apoptosis speck-like protein(ASC)and cysteinyl aspartate specific proteinase(Caspase)-1 were analyzed by Western blot.Results YLSC could significantly alleviate the pathological damages induced by isoproterenol.Compared with the model group,the contents of SOD,CAT and GSH-Px were increased,while the levels of MDA,cTnT,CK-MB,TNF-α,IL-6,IL-1βand IL-18 were decreased in YLSC groups(P<0.05 or P<0.01).Western blot showed that the protein expressions of NLRP3,ASC and Caspase-1 in YLSC groups were lower than those in model group(P<0.05 or P<0.01).YLSC pretreatment ameliorated these changes in a dose-dependent manner.Conclusions YLSC could protect against myocardial ischemia induced by isoproterenol,and its mechanism might be associated with the inhibition of oxidative stress,reduction of TNF-α,IL-6,IL-1βand IL-18,and inactivation of NLRP3 inflammasome.

关 键 词：玉郎伞查尔酮 心肌缺血 氧化应激 炎症反应 NLRP3炎症小体 

分 类 号：R972[医药卫生—药品]