依帕司他对醛糖还原酶和核转录因子-κB表达及血管平滑肌细胞增殖的影响

Influence of epalrestat on aldose reductase, NF-κB expression and vascular smooth muscle cell proliferation

目的研究依帕司他对醛糖还原酶(AR)、核转录因子(NF)-κB表达及血管平滑肌细胞(VSMC)增殖的影响,探讨依帕司他抗细胞增殖的可能机制。方法取大鼠胸主动脉段行VSMC培养,用高浓度葡萄糖(22.5mmol/L)诱导AR基因表达,然后加入不同浓度的依帕司他,培养3d后行VSMC计数,并用免疫组化、RT-PCR及原位杂交的方法检测NF-κB及AR的表达。结果①随依帕司他浓度的增加,VSMC计数逐渐减少。②高浓度葡萄糖时NF-κB表达强阳性,加入不同浓度的依帕司他后,NF-κB表达逐渐减弱。③高浓度葡萄糖可明显诱导AR基因表达,依帕司他对其表达有抑制作用,且呈剂量依赖性。结论①高浓度葡萄糖可促进VSMC增殖,依帕司他可抑制这一增殖作用,且具有剂量依赖性。②依帕司他可抑制AR及NF-κB的表达。③依帕司他可能是通过抑制AR及NF-κB的表达继而抑制VSMC的增殖。

Objective：To study the effects of epalrestat on aldose reductase （AR）, NF-κB expression and vascular smooth muscle cells （VSMC） proliferation and to discuss the possible mechanisms of VSMC proliferation resisted by epaIrestat. Method： AR expression was induced by high concentration of glucose（22.5 mmol/L）in the rat VSMC. Then different concentration of epalrestat was used to inhibited them. The number of VSMCs was calculated with adding different concentration of glucose after three days cultivation. RT-PCR, immunohistochemical methods and in situ hybridization were used to examine NF-κB and AR expression. Result： （1） The number of VSMCs was decreased gradually with the increasing of the concentration of epalrestat. （2） NF-κB was increased singnificantty at high concentration of glucose. Its expression was decreased as added with different concentration of epalrestat. （3）AR expression was induced by high concentration glucose and inhibited by epalrestat with dose dependent. Conclusion： AR and NF-κB expression and VSMC proliferation were induced by high concentration of glucose and inhibited by epalrestat with dose dependent.