摘 要: 目的 观察肿瘤坏死因子-α(TNF-α)单克隆抗体(英夫利西)对矽尘诱导的大鼠肺纤维化的抑制作用,探讨英夫利西治疗肺纤维的可能机制。方法 将48只雄性Wistar大鼠随机分为3组,每组16只:染尘组和干预组大鼠气管内一次性注入50mgSiO2粉尘,次日起干预组给予15mg/kg英夫利西皮下注射,共5天,染尘组仅注射等量生理盐水;对照组气管内和皮下均注射生理盐水。各组分别于建模后7d、14d 处死大鼠各8只,以HE、Masson染色对肺组织炎症和纤维化程度进行评价。ELISA法检测血、BALF中TNF-α含量,Western-blot检测肺组织NF-κB蛋白表达量。结果 英夫利西干预后,肺泡炎评分(7d)和纤维化评分(14d)优化;血清TNF-α含量降低,BALF TNF-α含量仅7d降低, 7d 时NF-κB p65蛋白表达下调,以上结果差异均具有统计学意义(P<0.05)。结论 TNF-α单克隆抗体可降低TNF-α水平,进而抑制NF-κB信号通路的活化,缓解矽尘诱导的大鼠肺纤维化进程。 |
关键词: 英夫利西 肿瘤坏死因子-α(TNF-α) 核因子-κB信号通路 矽肺 |
中图分类号: R135.2
文献标识码:
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基金项目: 2012年青岛市科技发展指导计划项目(KJZD-12-23-nsh) |
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Interventive effect of TNF–α monoclonal antibody on silica-induced pulmonary fibrosis in rats |
ZHANG Hua, GAO Lei, TAN Rui-xia, SUI Jun-na , GUO Jian
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Center of Occupational Disease Prevention and Control, Qingdao Municipal Central Medical Group , Qingdao 266042, China
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Abstract: Objective To observe the inhibiting effect of TNF–α monoclonal antibody(infliximab)on silica-induced pulmonary fibrosis in rats, to explore the possible mechanism of infliximab in silicosis treatment. Methods Forty-eight Wistar rats were randomly divided into treatment group (n=16), model group (n=16) and control group (n=16). 50mg SiO2 dusts were injected into trachea of the rats of silica-exposed group and intervention group, from the second day of silica-exposure the rats of intervention group received 15mg/kg by S.C injection of infliximab for 5 days, the rats of silica-exposed group were injected with N.S; while the control rats only administrated with N.S both trachea and subcutaneous injection. 7 and 14 days later after silica exposure, 8 rats of each group were killed, respectively, the lung tissue were stained with H&E and Masson’s trichromedye for observing inflammation and fibrosis, TNF-α levels in serum and bronchoalveolar lavage fluid (BALF) were measured with enzyme linked immunosorbent assay (ELISA), NF-κBp65 expression was measured quantitatively by Western bloting method. Results The results showed that after intervention of infliximab, the severity of pulmonary inflammation and fibrosis all were improved, the levels of serum TNF-α(7d, 14d) and BALF TNF-α (7d) were decreased, and the rising of NF-κB p65 protein expression (7d) was also inhibited (P <0.05). Conclusion The results suggested that TNF–α monoclonal antibody can reduce TNF–α level, inhibit NF-κB signal pathway and alleviate the progress of pulmonary fibrosis by silica in rats. |
Keywords: Infliximab tumor necrosis factor-α (TNF-α) nuclear factor-κB(NF-κB) silicosis |