大黄素对IL-1β诱导血管平滑肌细胞增殖的影响及机制研究

Effect of Emodin on IL-1β-induced Proliferation of Vascular Smooth Muscle Cells and the Underlying Mechanism

【目的】观察大黄素对IL-1诱导下血管平滑肌细胞增殖的影响并探讨其作用机制。【方法】将IL-1β作用于平滑肌细胞，并用大黄素进行干预，实验设置对照组、IL-1β组、大黄素干预组。MTT法检测各组细胞的增殖能力；流式细胞术检测各组细胞的周期变化；RT-PCR检测各组细胞PCNA、CyclinDlmRNA的表达；west—ernblot检测各组细胞PCNA、CyclinDl蛋白的表达以及JAK2、STAT3的磷酸化情况。【结果】与对照组相比1171p组细胞的增殖能力显著增加（P〈0．01），与IL-1β组相比大黄素干预组细胞的增殖能力显著降低（P〈0．01）。IL-1β组S期细胞所占比例（50．71±4．17）％，显著高于对照组（30．91±2．04）％（P〈0．01）。大黄素干预组S期细胞所占比例（32．34±4．35）％，显著低于IL-1β组（P〈0．05），同时其G～G1期细胞所占比例（48．83±4．55）％显著高于IL-1β组的（33．88±1．67）％（P〈O．01）。与对照组相比IL-1β组PCNA、CyclinDlmRNA以及蛋白的表达都显著升高（P〈O．01），而大黄素干预组PCNA、CyclinDlmRNA以及蛋白的表达显著低于II，1口组（P〈0．05）。与对照组相比IL-1β组JAK2、STAT3蛋白磷酸化程度显著增加（P〈O．05），与IL-1β组相比大黄素干预组JAK2、STAT3蛋白磷酸化程度显著降低（P〈0．05）。【结论】大黄素能够抑制IL-1β诱导的血管平滑肌细胞增殖，并且其抑制作用与JAK2／8TAT3信号通路的阻断有关。

[Objective]To observe the effect of emodin on IIT1β-induced proliferation of vascular smooth muscle cells（VSMCs） and explore its possible mechanism. [Methods]VSMCs were treated by IL-1/3 and inter- vened by emodin. Three experimental groups including the control group, IL-1β treatment group and the IL- 1β plus emodin treatment group were used in this study. MTT assay was used to detect the cell proliferation. Flow cytometry was used to examine the cell cycles. RT-PCR was used to examine the mRNA expression of PCNA and CyclinD1. The protein expression of PCNA and CyclinD1 and the phosphorylation of JAK2 and STAT3 were examined by using Western blot analysis. [Results] Compared with control group, the cell prolif- eration in IL-1β treatment group significantly increased（ P 〈0.01）. Compared with IL-1β treatment group, the ceil proliferation in emodin treatment group significantly decreased（ P 〈0.01）. The proportion of ceils in S phase of emodin treatment group was 32. 340/00 ±4.35% which was obviously lower than that in IL-113 treat- ment group（ P 〈0.05）. Meanwhile the proportion of ceils in Go 〈G1 phase in emodin treatment group was significantly higher than that in IL-1β treatment group（48.83 %± 4.55 % vs 33.88 % ± 1. 67 %, P d0.01 ）. Compared with control group, the mRNA and protein expression of PCNA and CyclinD1 in IL-1β treatment group increased significantly（ P 〈0. 01）, while those in emodin treatment group were significantly lower than those in IL-1β treatment group（ P 〈0.05）. Compared with control group, the phosphorylation of JAK2 and STAT3 in IL-1β treatment group increased significantly（ P 〈0.05）. Compared with IL- 1β treatment group, the phosphorylation of JAK2 and STAT3 in emodin treatment group decreased significantly（ P d0.05）. [Con clusion] Emodin can inhibit the proliferation of VSMCs induced by IL-1β, which may be related with the blockage of the signal transduetion of JAK2/STAT3.