盐酸曲美他嗪对心肌缺血再灌注大鼠Fas、FasL基因表达的影响

Effect of trimetazidine hydrochloride on Fas,Fas L gene expression of myocardial ischemia and reperfusion rats

目的通过对心肌缺血再灌注模型大鼠应用盐酸曲美他嗪,探究其对心肌细胞Fas、Fas L基因表达情况的影响。方法选取44只成年健康雄性大鼠,采取随机数表法分组,正常组11只,不予任何药物及手术治疗,模型组11只,建立心肌缺血再灌注模型,实验组及对照组各11只,在模型组基础上于缺血前5 min分别注射盐酸曲美他嗪10 mg、1%磷酸盐缓冲液300 UI,试验后各组通过缺口末端标记法检测心肌细胞凋亡水平,并通过PCR逆转录聚合酶链反应检测Fas、Fas L基因表达水平。结果大鼠心肌区形态变化提示盐酸曲美他嗪处理对大鼠心肌缺血再灌注损伤能产生一定的保护作用。免疫组化分析显示对照组心肌间质只有散在染色极浅的弱阳性反应。模型组与对照组Fas、Fas L表达较明显,与实验组比较,实验组表达较低。实验组与对照组均有不同程度坏死基因表达,且实验组Fas表达(0.23±0.17)、Fas L表达(0.21±0.09)、坏死面积(23.41±5.37)与对照组Fas表达(0.59±0.16)、Fas L表达(0.51±0.04)、坏死面积(41.66±4.19)比较显著降低,差异有统计学意义(P<0.05);实验组与对照组心肌组织电泳结果均不同程度表达,实验组较对照组Fas/Fas L mRNA的水平明显降低。结论盐酸曲美他嗪能够明显降低心肌细胞缺血后再灌注的凋亡损伤水平,并通过抑制Fas、Fas L基因的表达,减缓心肌再灌注损伤,对心肌缺血疾病治疗具有指导意义,值得临床推广。

Objective To investigate the effect of trimetazidine hydrochloride on Fas,Fas L gene expression of myocardial ischemia and reperfusion rats. Methods 44 healthy adult male rats were selected and divided into four groups according to a random number table method: 11 rats in the normal group treated without any drugs and surgery; 11 rats in model group of myocardial ischemia and reperfusion; 11 rats in experimental group injected with trimetazidine hydrochloride and 11 rats in control group injected with 1% phosphate buffer on the basis of model group treatment 5min before ischemia.Myocardial apoptosis levels were detected by nick end labeling,and Fas,Fas L gene expression levels were detected by PCR reverse transcription polymerase chain reaction. Results Morphological changes of rat myocardial region suggest Qu Mei hydrochloride trimetazidine treatment on myocardial ischemia reperfusion injury in rats can produce a protective effect. Immunohistochemical analysis showed that the control group myocardial interstitial only scattered in the extremely shallow weak positive staining reaction. The model group and the control group Fas,Fas L expression significantly,compared with the experimental group,the experimental group had low expression. The experimental group and the control group had varying degrees of necrosis gene expression,and Fas expression( 0. 23 ± 0. 17),Fas L expression( 0. 21 ± 0. 09),necrotic area( 23. 41 ± 5. 37) of the experimental group were lower than those of the control group,Fas expression( 0. 59 ± 0. 16),Fas L expression( 0. 51 ± 0. 04),necrotic area( 41. 66 ± 4. 19),and the differences were statistically significant( P < 0. 05); after the test,myocardial tissue electrophoresis results showed a different levels of expression in the experimental group and the control group,The experimental group was significantly lower than the control group Fas / Fas L level of mRNA. Conclusion Trimetazidine hydrochloride could significantly reduce the level of myocardial ischemia and reperfusion apoptosis,and slow myocardial reperfusion injury by suppressing the expression of Fas,Fas L gene,which has the guiding significance for the treatment of myocardial ischemia disease.