白藜芦醇对银屑病HaCaT细胞增殖、凋亡及STAT3信号通路的影响

Effects of Resveratrol on Proliferation,Apoptosis in HaCaT Cells via STAT3 Signaling Pathway

目的研究白藜芦醇(RES)抑制HaCaT细胞增殖及促进凋亡的作用及其对STAT3信号通路的调控作用,探讨RES治疗银屑病的作用机制。方法体外培养HaCaT细胞,加以不同浓度RES干预。通过检测细胞增殖和凋亡、STAT3通路相关基因(STAT3、PIM1、Bax、Bcl-2、Cyclin D1)以及STAT3磷酸化蛋白表达水平影响。结果倒置显微镜观察提示,RES能够抑制HaCaT细胞增殖。MTT法结果显示,低浓度RES对HaCaT细胞活力无明显影响,而高浓度RES随浓度增加细胞活力明显降低,同时呈现一定的剂量和时间依赖(P<0.05)。FCM结果显示,加入RES后,凋亡的细胞数量可明显增加。Western blot结果显示,RES可升高凋亡相关基因Bax/Bcl-2的表达(P<0.01),显著抑制PIM1及STAT3通路基因Cyclin D1、p-STAT3/STAT3的表达(P<0.01)。结论RES可有效抑制HaCaT细胞增殖及促进其凋亡,其作用机制可能与调控STAT3信号通路的活化有关,表明RES可通过缓解皮肤过度角化进而治疗银屑病。

Objective:To study the inhibitory effect of resveratrol(RES)on proliferation and apoptosis of HaCaT cells and its regulation on STAT3 signaling pathway,so as to explore the mechanism of RES in the treatment of psoriasis.Methods:HaCaT cells were cultured in vitro and treated with RES.The effects of RES on STAT3 signaling pathway in HaCaT cells were clarified by detecting cell proliferation and apoptosis,STAT3 pathway-related genes(STAT3,PIM1,Bax,Bcl-2,Cyclin D1)and STAT3 phosphorylated protein expression levels.Results:RES could inhibit the proliferation of HaCaT cells under inverted microscope.The results of MTT showed that low concentration RES had no significant effect on the activity of HaCaT cells,while high concentration RES decreased with the increase of concentration,and showed a certain dose-dependent and time-dependent(P<0.05).FCM results showed that the number of apoptotic cells was significantly increased after the addition of RES.Western blot results showed that RES can increase the expression of Bax/Bcl-2(P<0.01),and significantly inhibit the expression of PIM1,Cyclin D1,and p-STAT3/STAT3(P<0.01).Conclusion:RES can effectively inhibit the proliferation and promote the apoptosis of human immortalized epidermal HaCaT cells,and its mechanism may be related to regulating the activation of STAT3 signaling pathway,which indicates that RES can treat psoriasis by alleviating skin hyperkeratosis.