两型TNF-α及其受体在胸主动脉缩窄诱导压力负荷心肌肥厚小鼠中的表达

Expression of different type of TNF-α and TNF receptors in mice with pressure-overload cardiac hypertrophy models

目的检测压力负荷所致心肌肥厚小鼠模型心肌组织中两型TNF及其受体的表达。方法使用野生型BALB/c小鼠,将其分为假手术组(n=10只)和手术组(n=8只),通过胸主动脉缩窄术诱导压力负荷性心肌肥厚模型。术后2周处死小鼠,并对小鼠进行心脏形态学、血流动力学检测;使用Western Blot方法对心肌组织中两型TNF-α及其受体表达进行检测。结果(1)在BALB/c小鼠中成功建立胸主动脉缩窄诱导心肌肥厚模型;(2)术后2周手术组小鼠心脏组织中可见分泌型TNF-α和跨膜型TNF-α表达量均有增加,且分泌型TNF-α表达量明显高于跨膜型TNF-α,差异有统计学意义(P<0.05);(3)术后2周小鼠心脏组织中TNFR1和TNFR2表达量均有增加,但TNFR1表达量高于TNFR2(P<0.05)。结论在小鼠压力负荷诱导心肌肥厚模型中,两型TNF-α及其两种受体表达量均有增加。虽然起负性肌力作用的分泌型TNF-α及TNFR1表达起主导作用,其研究相对集中且广泛,但跨膜型TNF-α和TNFR2表达量增加提示其在这一病理过程中具有生物学作用。其作用和机制仍需进一步研究。

Objective The aim of this study is to detect expressions of soluble TNF-α, transmembrane TNF-α and their receptors in pressure-overload cardiac hypertrophy models induced by transverse aortic constriction （TAC）. Methods Pressure-overload cardiac hypertrophy model was induced in BABL/c mice by TAC. Sham served as a control. We characterized models by using morphological and hemodynamic analysis 14 days after surgery. Expression of sTNF-α, tmTNF-α, TNFR1 and TNFR2 in heart tissue was examined by Western Blot. Results （1） Pressure- overload cardiac hypertrophy model by TAC was successfully established. （2） Expression of sTNF-α and tmTNF-α was elevated in pressure-overload cardiac hypertrophy mice compared with the sham group. But the expression of sTNF-α was much higher than tmTNF-α. （3）Expression of TNFR1 and TNFR2 was upregulated in operation group compared with the sham group. But the expression of TNFR1 was much higher than TNFR2. Conclusion Expression of sTNF-α, tmTNF-α, TNFR1 and TNFR2 in heart tissue was elevated in pressure-overload cardiac hypertrophy group compared with the sham group. Although sTNF-α and TNFR1 play a dominant negative inotropic role in pressure overloaded hypertrophy model, which were relatively concentrated and widely researched, increased amount of tmTNF-α and TNFR2 points out a role of tmTNF-α in this pathological process. However, the biological actions of tmTNF-α and TNFR2 and the mechanisms in hypertrophy need to be further studied in the future.