塞来昔布对心肌肥厚大鼠TNF-α与心肌细胞凋亡的影响

The effect of celecoxib on TNF-α and apoptosis in myocardial hypertrophy in rats

目的探讨塞来昔布对压力超负荷性心肌肥厚大鼠肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)与心肌细胞凋亡之间的关系。方法将雄性Wister大鼠随机分为假手术2周组、假手术4周组、模型2周组、模型4周组、模型+塞来昔布2周组及模型+塞来昔布4周组。模型组进行腹主动脉缩窄手术,光镜下观察左心室组织切片、ELISA法检测血浆及心肌组织中的TNF-α、TUNEL法检测左心室心肌细胞的凋亡情况。结果 1左心室HE染色结果显示,模型组与假手术组相比,心肌细胞发生肥大且形态不规则,心肌肥厚程度明显加重,塞来昔布用药后可以逐渐缓解心肌肥厚。2在血浆中,各组大鼠2周和4周TNF-α含量差异无统计学意义(P>0.05);在心肌组织中,模型2周组大鼠的TNF-α含量显著升高(P<0.05),塞来昔布用药后可以降低TNF-α含量(P<0.05);4周时差异均无统计学意义(P>0.05)。3与假手术组比,模型组和塞来昔布组心肌细胞凋亡率显著升高(P<0.05),而塞来昔布用药后可以使心肌肥厚大鼠的凋亡率显著下降(P<0.05)。结论塞来昔布治疗心肌肥厚大鼠可能与炎症因子TNF-α和心肌细胞凋亡有关。

Objective To explore the effect of celecoxib on the relationship between tumor necrosis factor-α（ TNF-α） and apoptosis in pressure overload induced myocardial hypertrophy in rat.Methods Male Wister rats were divided into sham 2 weeks group,sham 4 weeks group,model 2 weeks group,model 4 weeks group,model plus celecoxib 2 weeks group and model plus celecoxib 4 weeks group in randomized order. The animal model was established by constriction of abdominal aorta. Left ventricular tissue sections were observed under light microscope. The contents of inflammatory cytokines TNF- α in plasma and tissue were examined by ELISA. TUNEL method was performed to detect the apoptosis of left ventricular myocardial cells. Results 1 Left ventricle HE staining showed that the myocardial cell hypertrophy and shape were irregular,myocardial hypertrophy was significantly heavier in model group,compared with control group. Celecoxib can gradually reduce myocardial hypertrophy. 2TNF-α levels in plasma were no significant differences between 2 weeks and 4 weeks groups（ P〈0. 05）.In the myocardial tissue,the content of TNF-α in model 2 weeks group were significantly increased（ P〈0. 05）. Celecoxib can reduce the the content of TNF-α levels（ P〈0. 05）. At 4 weeks,the differences were not statistically significant（ P〈0. 05）. 3 Compared with the control group,the apoptosis rate of myocardial cells in model group and celecoxib group were significantly increased（ P〈0. 05）,and celecoxib treatment can significantly decrease the apoptosis of myocardial hypertrophy in rats（ P〈0. 05）.Conclusion Celecoxib in the treatment of myocardial hypertrophy in rats may be related to the TNF-αand apoptosis of myocardial cells.