白细胞介素-6单克隆抗体抑制机械张力诱发小鼠增生性瘢痕

Interleukin-6 monoclonal antibody suppressed hypertrophic scar induced by mechanical tension

目的观察白细胞介素-6单克隆抗体（IL-6 mAb）对机械张力诱发的小鼠增生性瘢痕的作用。方法50只雄性C57/BL6小鼠，采取随机和均衡原则分为5组：正常对照组、假阳性组、建模组、IgG组、IL-6 mAb组，后3组小鼠予以机械张力处理，构建机械张力诱发的小鼠增生性瘢痕模型，张力持续2周后拆除装置，假阳性组无牵引张力。后2组于第3、4、5周分别予以免疫球蛋白G（IgG）和IL-6 mAb尾静脉注射，其他3组予以等量生理盐水替代注射。所有小鼠5周后处死，取瘢痕组织，利用形态学、组织学、分子生物学手段检测。结果与对照组比较，IgG对瘢痕增生无明显影响，IL-6 mAb组瘢痕面积明显缩小，组织学检测表明IL-6 mAb组胶原数量减少（均P＝0.000）。酶联免疫吸附试验（ELISA）结果显示IL-6 mAb下调促炎因子的表达（均P＝0.000）；实时定量反转录聚合酶链反应（RT-qPCR）及Western blot法检测进一步提示IL-6 mAb也能下调Ⅰ型胶原（ColⅠ）、Ⅲ型胶原（ColⅢ）的mRNA和蛋白表达（均P＝0.000）。结论IL-6 mAb可能通过抑制促炎因子分泌和抑制胶原的合成，抑制机械张力诱发的小鼠增生性瘢痕的形成。

ObjectiveTo study the effect of interleukin-6 monoclonal antibody （IL-6 mAb） on rats hyperplastic scar induced by mechanical tension.MethodsFifty male C57/BL6 rats were divided into five groups according to random and equilibrium principles： normal control group, sham positive group, model group, IgG group, IL-6 mAb group. The latter 3 groups of rats were applied mechanical tension to build rats model of hyperplastic scar induced by mechanical tension, tension lasting for 2 weeks before dismantling device, rats in sham positive group were not applied mechanical tension. In the third, fourth and fifth week, rats in the latter 2 groups were injected with IgG and IL-6 mAb through tail intravenous, respectively. However, the ones in the other three groups were injected with the same volume saline instead. All rats were executed after 5 weeks, cut the scar tissue, and detection was made using the morphology, histology, molecular biology method.ResultsCompared with control group, the IgG had no obvious effect on hyperplasia scar, nevertheless, in IL-6 mAb group, scar area was significantly narrowed, histological tests showed the decrease in the contents of collagen in IL-6 mAb group （all P=0.000）. Enzyme linked immunosorbent assay （ELISA） showed that IL-6 mAb reduced the expression of proinflammatory factor （all P=0.000）; real-time quantitative PCR （RT-qPCR） and Western blotting indicated that IL-6 mAb could also knock down mRNA and protein expression of type Ⅰ collagen （Col Ⅰ） and Ⅲ collagen （Col Ⅲ） （all P=0.000）.ConclusionIL-6 mAb could inhibit rats hyperplastic scar formation induced by mechanical tension, probably through inhibiting the secretion of proinflammatory factor and the synthesis of collagen.