丁苯酞对自发性高血压大鼠心肌损伤的影响研究

Study on the therapeutic effects of butylphthalide on myocardial injury in spontaneously hypertensive rats

目的探究丁苯酞(butylphthalide,NBP)对自发性高血压大鼠(spontaneously hypertensive rat,SHR)心肌损伤的影响,并探讨其对核因子(nuclear factor,NF)-κB/NOD样受体热蛋白结构域(NOD-like receptor pyrin domain containing,NLRP)3通路的调控作用。方法将SHR分为模型组、卡托普利(captopril,Cap)组、低中高剂量NBP(20、40、80 mg/kg)组,食用油溶解后灌胃给药,每组7只;另选取7只雄性Wistar-Kyoto大鼠作为对照组,对照组和模型组均给予等量的食用油。给药5周后,称量体质量、左心室重量,计算左心室重量指数;测量收缩压、舒张压、左室舒张末压;苏木精-伊红染色观察心脏组织病理学变化;酶联免疫吸附试验检测透明质酸(hyaluronic acid,HA)和Ⅲ型胶原N端肽(typeⅢcollagen N-terminal peptide,PⅢNP)水平;定量反转录聚合酶链反应和蛋白免疫印迹检测NF-κB/NLRP3/白介素(interleukin,IL)-1β信使RNA(messenger RNA,mRNA)和蛋白水平。结果与对照组相比,模型组心肌纤维广泛溶解、排列紊乱,间质受损,心脏组织中HA、PIIINP、NF-κB、NLRP3、IL-1βmRNA及蛋白水平均显著升高(P<0.01);与模型组相比,Cap组、低中高剂量NBP组大鼠心肌损伤改善,HA、PIIINP、NF-κB、NLRP3、IL-1βmRNA及蛋白水平显著降低(P<0.01)。结论NBP可能通过抑制NF-κB/NLRP3/IL-1β通路表达来减轻SHR心肌纤维化及炎症损伤程度,从而达到保护心脏的作用。

Objective To investigate the effects of butylphthalide(NBP)on myocardial injury in spontaneously hypertensive rats(SHR)and its regulation on nuclear factor(NF)-κB/NOD-like receptor pyrin domain containing(NLRP)3 pathway.Methods SHR were divided into model group,captopril(Cap)group and low,medium and high dose NBP(20,40,80 mg/kg)groups.After dissolving the drugs with edible oil,the rats were given by gavage(7 rats/group).Seven male Wistar-Kyoto rats were selected as the control group,both control group and model group were given the same amount of edible oil.After 5 weeks of administration,the body weight and left ventricular weight were measured,and the left ventricular mass index was calculated.Systolic blood pressure,diastolic blood pressure,left ventricular end diastolic pressure were measured.Hematoxylin-eosin staining was used to observe the pathological changes of the heart.Enzymelinked immunosorbent assay was used to detecte the levels of hyaluronic acid(HA)and typeⅢcollagen N-terminal peptide(PⅢNP).Quantitative reverse transcription polymerase chain reaction and western blot were used to detect the messenger RNA(mRNA)and protein levels of NF-κB/NLRP3/IL-1β.Results Compared with the control group,myocardial fibers in the model group were widely dissolved,arranged disorderly,and interstitial was damaged,the mRNA and protein levels of HA,PⅢNP,NF-κB,NLRP3 and IL-1βin heart tissue were significantly increased(P<0.01).Compared with the model group,the myocardial injury was improved in Cap group and low,medium and high dose NBP groups,the mRNA and protein levels of HA,PⅢNP,NF-κB,NLRP3 and IL-1βwere significantly decreased(P<0.01).Conclusions NBP may reduce the degree of myocardial fibrosis and myocardial inflammatory damage in SHR by inhibiting the expression of NF-κB/NLRP3/IL-1βpathway,so as to protect the heart.