丁苯酞对慢性心肌缺血大鼠心肌细胞凋亡的影响

Effect of n-butylphthalide on myocardial cell apoptosis in rats with chronic myocardial ischemia

目的探讨丁苯酞对慢性心肌缺血(CMI)大鼠心肌细胞凋亡的影响。方法将50只健康雄性Wistar大鼠采用随机单位组设计分组法分为对照(CO)组、模型(MO)组、低剂量丁苯酞(L-NBP)组、中剂量丁苯酞(M-NBP)组和高剂量丁苯酞(H-NBP)组,每组10只。L-NBP组和H-NBP组大鼠分别腹腔注射3、6、12 mg/kg丁苯酞氯化钠注射液,CO组连续14 d腹腔注射等量的0.9%氯化钠,使用超声心动图评价各组大鼠制模后心功能变化,检测凋亡相关蛋白表达水平和凋亡相关mRNA的表达情况。结果CMI模型制备完成后,MO组LVEF水平低于CO组,差异有统计学意义(P<0.001)。L-NBP组、M-NBP组和H-NBP组大鼠LVEF水平高于MO组,差异有统计学意义(P<0.001)。MO组的TUNEL阳性细胞数大于CO组,差异有统计学意义(P<0.001)。此外,H-NBP组的TUNEL阳性细胞数量小于MO组、L-NBP组和M-NMP组,差异有统计学意义(P<0.001)。MO组Bax和cleaved Caspase-3蛋白表达水平高于CO组,Bcl-2蛋白表达水平低于CO组,差异有统计学意义(P<0.05)。L-NBP组、M-NBP组和H-NBP组的Bax和cleaved Caspase-3蛋白表达水平低于MO组,Bcl-2蛋白水平高于MO组,差异有统计学意义(P<0.05)。H-NBP组Bax和cleaved Caspase-3蛋白表达低于L-NBP组和M-NBP组,Bcl-2表达水平高于L-NBP组和M-NBP组,差异有统计学意义(P<0.05)。细胞凋亡相关mRNA的表达也表现出相同的变化趋势。结论丁苯酞可有效降低CMI大鼠心肌细胞凋亡水平,改善心功能,其效果与丁苯酞剂量相关。

Objective To investigate the effect of n-butylphthalide(NBP)on myocardial cell apoptosis in rats with chronic myocardial ischemia(CMI).Methods Fifty healthy male Wistar rats were divided into control(CO)group,model(MO)group,low-dose n-butylphthalide(L-NBP)group,medium dose n-butylphthalide(M-NBP)group and high-dose n-butylphthalide(H-NBP)group using the randomized unit group design grouping method,with 10 cases in each group.Intraperitoneal injections of 3,6 and 12 mg/kg Butylphthalide and Sodium Chloride Injection were administered once per day to rats in the L-NBP group,M-NBP group and H-NBP group respectively.CO group received an equal volume of 0.9%Sodium Chloride via intraperitoneal injection for 14 consecutive days.Evaluate the changes in cardiac function of rats in each group after modeling using echocardiography,and detect the expression levels of apoptosis related proteins and apoptosis related mRNA.Results After the preparation of the CMI model,the LVEF level in the MO group was lower than that in the CO group,with statistically significant difference(P<0.001).The LVEF level of rats in the L-NBP group,M-NBP group and H-NBP group was higher than that in the MO group,with statistically significant difference(P<0.001).The number of TUNEL positive cells in the MO group was higher than that in the CO group,with statistically significant difference(P<0.001).In addition,the number of TUNEL positive cells in the H-NBP group was lower than that in the MO group,L-NBP group and M-NMP group,with statistically significant difference(P<0.001).The expression levels of Bax and cleaved Caspase-3 proteins in the MO group were higher than those in the CO group,while the expression level of Bcl-2 protein was lower than that in the CO group,with statistically significant differences(P<0.05).The expression levels of Bax and cleaved Caspase-3 proteins in the L-NBP group,M-NBP group and H-NBP group were lower than those in the MO group,while the Bcl-2 protein level was higher than that in the MO group,with statistically significant differences(P<0.05).The expression levels of Bax and cleaved Caspase-3 proteins in the H-NBP group were lower than those in the L-NBP group and M-NBP group,while the expression level of Bcl-2 was higher than that in the L-NBP group and M-NBP group,with statistically significant differences(P<0.05).The expression of apoptosis related mRNA also showed the same trend of change.Conclusion NBP can effectively reduce the level of myocardial cell apoptosis and improve cardiac function in CMI rats,and its effect is related to the dosage of NBP.