灯盏花素对心肌缺血再灌注损伤大鼠的心肌保护作用

Protective effect of breviscapine on myocardial ischemia-reperfusion injury in rats

目的观察灯盏花素对心肌缺血再灌注损伤(myocardial ischemia-reperfusion injury,MIRI)大鼠的心肌保护作用,并探讨其可能的机制。方法将60只SD大鼠随机分为健康组、模型组、灯盏花素低剂量和灯盏花素高剂量组,各15只;灯盏花素低剂量、灯盏花素高剂量组大鼠腹腔注射灯盏花素(50、100 mg·kg^(−1));健康组、模型组大鼠腹腔注射等体积生理盐水。每日1次,干预5 d。模型组、灯盏花素低剂量组、灯盏花素高剂量组最终均纳入10只大鼠。检测心电图指标;2,3,5-氯化三苯基四氮(2,3,5-tri⁃phenyltetrazolium chlorid,TTC)染色检测心肌梗死面积;检测血清心肌损伤指标;检测血清氧化应激指标;检测血清炎性因子水平;蛋白质印迹法(Western blotting)检测心肌组织白细胞介素-23(interleukin-23,IL-23)、白细胞介素-17(interleukin-17,IL-17)蛋白的表达水平。结果与模型组比较,灯盏花素低剂量组大鼠室颤(ventricular fibrillation,VF)和室性心动过速(ventricular tachycardia,VT)发生次数、血清肌酸激酶同工酶(creatine kinase isoenzyme,CK-MB)活性、心肌肌钙蛋白T(cardiac troponin T,cTnT)活性、丙二醛(malondialdehyde,MDA)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)、心肌组织IL-23及IL-17蛋白的表达水平降低,VF、VT持续时间缩短,血清超氧化物歧化酶(superoxide dismutase,SOD)活性升高(P<0.05);灯盏花素低剂量组和灯盏花素高剂量组各指标水平变化规律相同,灯盏花素变化高剂量组变化更显著(P<0.05)。结论灯盏花素可缓解MIRI大鼠心律失常、减轻心肌损伤及氧化应激反应和炎症反应。推测其作用机制可能与抑制IL-23/IL-17轴活性有关。

Objective To observe the myocardial protective effect of breviscapine on myocardial ischemia-reperfusion injury(MIRI)in rats,and to explore the possible mechanism.Methods Sixty SD rats were randomly divided into healthy group,model group,lowdose and high-dose groups of breviscapine,15 rats in each.The rats in the low and high dose groups of breviscapine were intraperitoneally injected with breviscapine(50,100 mg·kg^(−1)).Rats in the healthy group and model group were intraperitoneally injected with an equal volume of normal saline.Once a day,the intervention lasted for 5 days.Ten animals were included in the model group,lowdose and high-dose groups of breviscapine.The electrocardiogram,serum myocardial injury indicators,serum oxidative stress indicators,and the serum inflammatory factors were detected.The myocardial infarct size was detected by 2,3,5-triphenyltetrazolium chlorid(TTC)staining.The protein expressions of interleukin-23(IL-23)and interleukin-17(IL-17)in myocardial tissue was detected by Western blotting method.Results Compared with the MIRI group,the number of the occurrences of ventricular fibrillation(VF),ventricular tachycardia(VT),serum creatine kinase isoenzyme(CK-MB)activity,cardiac troponin T(cTnT)activity,malondialdehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)levels,myocardial tissue IL-23,IL-17 protein expression were decreased,the VF and VT continued time were reduced,and the serum superoxide dismutase(SOD)activity was increased in the low-dose group of breviscapine(P<0.05).Low-dose group of breviscapine and high dose group of breviscapine had the same changes in various indices,and high dose group of breviscapine was more significant(P<0.05).Conclusion Breviscapine can relieve arrhythmia,reduce myocardial damage,oxidative stress and inflammation in MIRI rats,and its mechanism of action may be related to the inhibition of IL-23/IL-17 axis activity.