调控Wnt信号通路对百草枯中毒大鼠肺纤维化的影响

发布时间：2018-05-07 16:48

本文选题：Wnt信号通路 + 百草枯　；参考：《医学研究生学报》2017年03期

【摘要】：目的百草枯中毒患者可因不可逆的肺纤维化而死亡,而Wnt信号通路参与了肺纤维化的发生发展。文中通过建立百草枯中毒大鼠模型,探讨Wnt信号通路在百草枯中毒大鼠肺纤维化中的作用。方法选用健康雄性SD大鼠36只,随机数字表法分为对照组、百草枯中毒组和抑制剂组,每组12只。百草枯中毒组大鼠采用一次性腹腔注射百草枯20 mg/kg建立百草枯中毒大鼠肺纤维化模型,对照组给予腹腔注射等量等渗盐水,抑制剂组采用一次性腹腔注射百草枯20 mg/kg同时经气道给予Wnt信号通路抑制剂DKK1(2 mg/kg,100μL PBS)。3组均第28天处死大鼠,取出肺组织常规进行HE染色和马松染色,利用Ray Bio蛋白芯片技术检测对照组和百草枯中毒组相关蛋白表达情况,利用Western blot技术检测各组Wnt信号通路关键蛋白β-catenin和MMP-2的表达。结果百草枯中毒组HE染色和马松染色结果示:肺泡结构紊乱,炎症细胞浸润,胶原纤维沉积,抑制剂组较百草枯中毒组肺纤维化程度明显减轻,胶原蛋白沉积减少,而对照组肺泡结构清晰,无胶原纤维沉积。Ray Bio蛋白芯片技术结果示百草枯中毒组肺组织IL-1β、PDGF、β-catenin、MMP-2和TGF-β1表达水平异常升高。与对照组β-catenin、MMP(0.31±0.03,0.28±0.07)比较,百草枯中毒组(0.82±0.09,1.04±0.08)升高,抑制剂组(0.56±0.06,0.63±0.05)降低(P0.05)。与百草组中毒组比较,抑制剂组β-catenin、MMP表达均降低(P0.05)。结论百草枯可诱导大鼠发生肺纤维化,导致Wnt信号通路高度激活,通过抑制Wnt信号通路能够减弱肺纤维化的程度。
[Abstract]:Objective: paraquat poisoning patients may die of irreversible pulmonary fibrosis, and the Wnt signaling pathway is involved in the development of pulmonary fibrosis. The role of Wnt signaling pathway in pulmonary fibrosis of paraquat poisoned rats was studied by establishing a paraquat poisoning model. Methods Thirty-six male Sprague-Dawley rats were randomly divided into control group, paraquat poisoning group and inhibitor group with 12 rats in each group. The pulmonary fibrosis model of paraquat poisoned rats was established by intraperitoneal injection of paraquat for 20 mg/kg in the paraquat poisoning group, and isosmotic saline was injected intraperitoneally in the control group. In the inhibitor group, paraquat was injected intraperitoneally for 20 mg/kg and Wnt signaling pathway inhibitor DKK1(2 mg / kg ~ (100 渭 L) PBS).3 was administered through the airway. The rats in the control group were killed on the 28th day. The lung tissues were taken out for HE staining and Ma Song staining. The expression of related proteins in control group and paraquat poisoning group was detected by Ray Bio protein chip technique, and the expression of 尾 -catenin and MMP-2 in Wnt signaling pathway was detected by Western blot technique. Results the results of HE staining and Ma Song staining in paraquat poisoning group showed that pulmonary alveolar structure disorder, inflammatory cell infiltration, collagen fiber deposition, pulmonary fibrosis and collagen deposition in inhibitor group were significantly less than those in paraquat poisoning group. In the control group, the alveolar structure was clear and the expression levels of IL-1 尾 -PDGF, 尾 -cateninine MMP-2 and TGF- 尾 1 in the lung tissue of paraquat poisoning group were increased abnormally without collagen deposition. Compared with the control group, 尾 -cateninine (MMPN) 0.31 卤0.03 (0.28 卤0.07), paraquat poisoning (0.82 卤0.09) 1.04 卤0.08) and inhibitor group (0.56 卤0.06 卤0.63 卤0.05) decreased P0.05N. Compared with the control group, the expression of 尾 -cateninine MMP in the inhibitor group was significantly lower than that in the control group. Conclusion Paraquat can induce pulmonary fibrosis in rats, which leads to high activation of Wnt signaling pathway, which can reduce the degree of pulmonary fibrosis by inhibiting Wnt signaling pathway.
【作者单位】：南方医科大学金陵医院(南京军区南京总医院)急救医学科;
【基金】：国家自然科学基金(81401583) 北京协和医学基金会睿E(睿意)急诊医学科研基金(R2014004) 全军后勤面上项目(CNJ14L002) 南京军区南京总医院科研基金(2015027)
【分类号】：R595.4

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