重组人IL-10抑制TNF-α和PDGF-BB所致大鼠血管平滑肌细胞增殖

目的:观察重组人白介素10(rhIL-10)对SD大鼠血管平滑肌细胞及血管损伤后新生内膜增殖的影响。方法:培养大鼠主动脉血管平滑肌细胞,采用MTS/PES法确定血管平滑肌细胞的增殖状态,应用流式细胞术测定细胞周期。利用大鼠血管损伤模型,观察rhIL-10对新生内膜增殖的影响。结果:与对照组相比,rhIL-10单独应用对血管平滑肌细胞生长没有影响(P>0.05)。rhIL-10可抑制在TNF-α和血小板源性生长因子分别刺激下的血管平滑肌细胞的生长(P<0.05)。流式细胞术测定的结果显示rhIL-10分别可以使TNF-α和PDGF-BB作用下的VSMC大部分处于G₀/G₁期,与对照组相比有明显差异(P<0.01)。大鼠颈动脉损伤后,rhIL-10治疗组的动脉血管新生内膜/中层面积比低于对照组约45%(P<0.01)。结论:抗炎细胞因子rhIL-10可抑制大鼠血管平滑肌细胞的增殖。

Recombinant human interleukin-10 inhibits vascular smooth muscle cell proliferation by TNF-α and PDGF-BB in vitro

AIM: To determine the effects of recombinant human interleukin-10(rhIL-10) on proliferation of vascular smooth muscle cells(VSMC) by TNF-α and PDGF-BB and neointimal hyperplasia after rat carotid arterial injury.METHODS: Rat aortic VSMC was cultured and treated with rhIL-10 with or without tumor necrosis factor-α(TNF-α) and platelet-derived growth factor-BB (PDGF-BB), respectively.Proliferation of VSMC was quantified by colormetric assay.Cell cycle analysis was performed by flow cytomertry.SD rats were treated with recombinant human IL-10(rhIL-10) for 3 days after carotid arteries injury.Neointima to media area ratio at the site of arterial injury was measured at 28 days after balloon injury.RESULTS: Compared to control,both TNF-α and PDGF-BB stimulated VSMC proliferation. rhIL-10 alone had no effect on VSMC growth.With TNF-α or PDGF-BB stimulation,rhIL-10,at dose as low as 10 μg/L,inhibited VSMC growth( P <0.05) for both cases.Cell number in G 0/G 1 phase of PDGF-BB and rhIL-10 co-treatment group was higher than those of PDGF-BB treatment alone( P <0.01) by flow cytometry analysis.The same results were observed in TNF-α and rhIL-10 co-treatment group( P <0.01).Compared with the arterial injury group,neotima/media area ratio of recombinant human IL-10 group was reduced at 45%( P <0.01).CONCLUSIONS: The anti-inflammatory cytokine rhIL-10 inhibits TNF-α and PDGF-BB-induced VSMC proliferation,respectively.These results suggest the possibility that recombinant human IL-10 as a potential therapeutic approach prevents neointimal hyperplasia.