蛇床子素预处理对大鼠心脏缺血再灌注损伤的作用

目的:探讨蛇床子素(osthole,Ost)预处理对大鼠心脏缺血再灌注损伤的作用及其机制。方法:建立大鼠心脏缺血再灌注损伤模型。30只雄性SD大鼠随机平均分为Ost组、模型组和假手术组。假手术组和模型组手术前1 h给予生理盐水(50 mg·kg~(-1),腹腔注射),Ost组缺血前1 h给予Ost(50 mg·kg~(-1),腹腔注射),模型组和Ost组血管夹夹闭左冠状动脉前降支,置于32℃温箱30 min后松开血管夹,4 h后收集各组大鼠心脏和血清。HE染色后观察心脏病理学形态学变化,Western blotting检测P38,p-P38和p-NF-κB;RT-PCR检测白细胞介素-6(interleukin-6,IL-6)、IL-1β和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的心脏表达和分泌;ELISA检测乳酸脱氢酶(lactic dehydrogenase,LDH)、心肌型肌酸激酶同工酶(creatine kinase-MB,CK-MB)、肌酸激酶(creatine kinase,CK)、IL-6、IL-1β和TNF-α的水平。结果:与假手术组比较,模型组病理改变,p-P38、p-NF-κB、LDH、CK-MB、CK、IL-6、IL-1β和TNF-α表达均明显增加(P0.05),但P38和NF-κB表达无明显差异。与模型组比较,Ost组病理改变,p-NF-κB、LDH、CK-MB、CK、IL-6、IL-1β和TNF-α表达明显减少(P0.05),但p-P38表达进一步增加,而P38和NF-κB表达仍无明显变化。结论:Ost预处理可通过抑制炎症反应发挥对大鼠心脏缺血再灌注损伤的保护作用,其作用机制与促进P38信号通路激活相关。

The Effect and Potential Mechanism of Osthole Pretreatment in Myocardial Ischemia Reperfusion Injury

Objective:To explore the effect and potential mechanism of osthole in myocardial ischemia reperfusion injury.Methods:30 male SD rats were randomly divided into three groups.Sham group,model group,and osthole pretreatment group(Ost).The rats in model group and Sham group received saline before operation(50 mg · kg-1,intraperitoneally),while the rats in Ost group re ceived Ost(50 mg · kg 1,IP) 1 hour before operation.The rats in the model and Ost groups were kept in 32℃C infant incubators for 0.5 h after clamping their left anterior descending coronary artery,and then removed the clamp for reperfusion.The rats in Sham group underwent the same process,except for clamping left anterior descending coronary artery.These rats were sacrificed af ter 4 h of reperfusion.Blood samples and myocardial tissue were collected.The pathology of myocardial tissues was observed according to HE staining and the protein level of P38,p-P38,p-NF-κB were measured by Western blotting.Moreover,IL-6,IL-1 β and the expression and secretion of heart in TNF-oα were examined by RT-PCR and the levels of LDH,CK-MB,CK,IL-6,IL-1 β and TNF-α were exanimed by ELISA.Results:Compared with the Sham group,the histology change of myocardial,the protein expression level of p-P38and p-NF-κB,the expression of LDH,CK-MB,CK,IL-6,IL-1β and TNF-α in model group were significantly increased,but the protein expression level of P38 and NF-κB had no difference.But,compared with the model group,the histology change of myocardial,the protein expression level of p-NF-κB and the expression of LDH,CK-MB,CK,IL-6,IL-1 β and TNF-α in Ost group were significantly decreased with the expression of p-P38 further increased,but the protein expression level of P38and NF-κB still had no difference.Conclusion:Osthole pretreatment protect myocardial ischemia reperfusion injury from inflammation by inducing the activation of P38 signal pathway.