IL-38在大鼠肺间质纤维化模型中的作用研究
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摘要
目的采用气管内注射博来霉素(BLM)的方法构建大鼠肺间质纤维化模型,探讨IL-38在肺间质纤维化中的作用及意义。方法运用随机数字表法将60只健康Wistar大鼠分为盐水对照组(N组,20只)、单纯博来霉素组(B组,20只)、地塞米松干预组(D组,20只)。D组从第二天开始给予地塞米松腹腔注射,1次/日,连续至28天。光镜下观察肺组织的病理形态,测定大鼠血清、肺组织匀浆中IL-38表达量,采用RT-PCR法测定大鼠肺组织MIP-2的表达量。结果①D组肺损伤及肺纤维化程度较同期B组均明显减轻。②与同期N组对比,B、D组大鼠血清及肺组织匀浆中IL-38的表达量均减少(P <0. 05);与同期B组对比,D组大鼠血清及肺组织匀浆中IL-38的表达量均增加(P <0. 05)。③与同期N组对比,B、D组大鼠肺组织内MIP-2的表达量均增加(P <0. 05);与同期B组对比,D组大鼠肺组织内MIP-2的表达量减少。结论 IL-38表达不足在博来霉素致大鼠肺间质纤维化形成中有重要作用,通过刺激IL-38的表达,增加可能会改善大鼠肺间质纤维化程度。
Objective To construct a rat model of interstitial pulmonary fibrosis by intratracheal injection of bleomycin( BLM),and to explore the role and significance of IL-38 in pulmonary fibrosis. Methods 60 healthy Wistar rats were divided into the saline control group( the group N,20),the simple bleomycin group( the group B,20),and the dexamethasone intervention group( the group D,20 rats). The group D was daily given intraperitoneal injection of dexamethasone from the second day for 28 days. The pathological morphology of lung tissue was observed under light microscope,and the expression of IL-38 in serum and lung homogenate of rats was measured. The expression of MIP-2 in lung tissue of rats was measured by RT-PCR method. Results Lung injury and pulmonary fibrosis in the group D were significantly lower than those in the group B at the same time. Compared with the same period at the N group,the expression of IL-38 in serum and lung homogenate of the groups B and D decreased( P < 0. 05),and the expression of IL-38 in serum and lung homogenate of the group D increased( P < 0. 05).( 3) Compared with the N group,the expression of MIP-2 in the lung tissue of the groups B and D increased( P < 0. 05),and the expression of MIP-2 in the lung tissue of the group D decreased compared with that of group B at the same time. Conclusion The insufficient expression of IL-38 plays an important role in the formation of pulmonary fibrosis induced by bleomycin in rats. The increase of IL-38 expression may improve the degree of pulmonary fibrosis in rats.
Objective To construct a rat model of interstitial pulmonary fibrosis by intratracheal injection of bleomycin( BLM),and to explore the role and significance of IL-38 in pulmonary fibrosis. Methods 60 healthy Wistar rats were divided into the saline control group( the group N,20),the simple bleomycin group( the group B,20),and the dexamethasone intervention group( the group D,20 rats). The group D was daily given intraperitoneal injection of dexamethasone from the second day for 28 days. The pathological morphology of lung tissue was observed under light microscope,and the expression of IL-38 in serum and lung homogenate of rats was measured. The expression of MIP-2 in lung tissue of rats was measured by RT-PCR method. Results Lung injury and pulmonary fibrosis in the group D were significantly lower than those in the group B at the same time. Compared with the same period at the N group,the expression of IL-38 in serum and lung homogenate of the groups B and D decreased( P < 0. 05),and the expression of IL-38 in serum and lung homogenate of the group D increased( P < 0. 05).( 3) Compared with the N group,the expression of MIP-2 in the lung tissue of the groups B and D increased( P < 0. 05),and the expression of MIP-2 in the lung tissue of the group D decreased compared with that of group B at the same time. Conclusion The insufficient expression of IL-38 plays an important role in the formation of pulmonary fibrosis induced by bleomycin in rats. The increase of IL-38 expression may improve the degree of pulmonary fibrosis in rats.
引文
[1]江洪艳,赵勇.特发性肺间质纤维化治疗研究进展[J].临床肺科杂志,2016,21(5):910-912.
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[8]KORTHAGEN N M,VAN MOORSEL C H,KAZEMIER K M,et al.IL1RN genetic variations and risk of IPF:a meta-analysis and mRNA expression study[J].Immunogenetics,2012,64(5):371-377.
[9]PIGUET P F,VESIN C.Treatment by human recombinant soluble TNF receptor of pulmonary fibrosis induced by bleomycin or silica in mice[J].Eur Respir J,1994,7(3):515-518.
[10]徐翠平,柳爱华,宝福凯,等.白细胞介素-38的研究进展[J].中国病原生物学杂志,2015,10(5):476-479.
[11]VAN DE VEERDONK F L,STOECKMAN A K,WU G,et al.IL-38 binds to the IL-36 receptor and has biological effects on immune cells similar to IL-36 receptor antagonist[J].Proc Natl Acad Sci USA,2012,109(8):3001-3005.
[12]李丽娜,王华,周蕾,等.博莱霉素诱导小鼠肺间质纤维化造模方式的选择[J].中国免疫学杂志,2010,26(3):254-257.
[13]CHUA F,GAULDIE J,LAURENT G J.Pulmonary fibrosis:searching for model answers[J].Am J Respir Cell Mol Biol,2005,33(1):9-13.
[14]MOORE B B,HOGABOAM C M.Murine models of pulmonary fibrosis[J].Am J Physiol Lung Cell Mol Physiol,2008,294(2):L152-L160.
[15]蔡珊,陈平.巨噬细胞炎症蛋白与呼吸系统疾病[J].国外医学(呼吸系统分册),2002,22(4):175-177,181.
[16]STRIETER R M,GOMPERTS B N,KEANE M P.The role of CXCchemokines in pulmonary fibrosis[J].J Clin Invest,2007,117(3):549-556.
[17]GAO Q,LI Y,PAN X,et al.Lentivirus expressing soluble ST2 alleviates bleomycin-induced pulmonary fibrosis in mice[J].lnt Immunopharmacol,2016,30:188-193.
[18]TODD N W,LUZINA I G,ATAMAS S P.Molecular and cellular mechanisms of pulmonary fibrosis[J].Fibrogenesis Tissue Repair,2012,5(1):11.
[2]魏燕华,刘桂桃.肺纤维化的治疗进展[J].临床肺科杂志,2014,19(2):336-339.
[3]LIN H,HO A S,HALEY-VICENTE D,et al.Cloning and characterization of IL-1HY2,a novel interleukin-1 family member[J].JBiol Chem,2001,276(23):20597-20602.
[4]袁仙丽,李明才,李燕,等.白细胞介素-38及其相关细胞因子在炎症中的作用[J].中国细胞生物学学报,2013,35(8):1232-1237.
[5]DINARELLO C,AREND W,SIMS J,et al.IL-1 family nomenclature[J].Nat Immunol,2010,11(11):973.
[6]KUMAR S,MCDONNELL P C,LEHR R,et al.Identification and initial characterization of four novel members of the interleukin-1family[J].J Biol Chem,2000,275(14):10308-10314.
[7]徐飞,成述儒,罗玉柱.绵羊DRB1基因生物信息学分析[J].生物技术通报,2011,(1):113-118.
[8]KORTHAGEN N M,VAN MOORSEL C H,KAZEMIER K M,et al.IL1RN genetic variations and risk of IPF:a meta-analysis and mRNA expression study[J].Immunogenetics,2012,64(5):371-377.
[9]PIGUET P F,VESIN C.Treatment by human recombinant soluble TNF receptor of pulmonary fibrosis induced by bleomycin or silica in mice[J].Eur Respir J,1994,7(3):515-518.
[10]徐翠平,柳爱华,宝福凯,等.白细胞介素-38的研究进展[J].中国病原生物学杂志,2015,10(5):476-479.
[11]VAN DE VEERDONK F L,STOECKMAN A K,WU G,et al.IL-38 binds to the IL-36 receptor and has biological effects on immune cells similar to IL-36 receptor antagonist[J].Proc Natl Acad Sci USA,2012,109(8):3001-3005.
[12]李丽娜,王华,周蕾,等.博莱霉素诱导小鼠肺间质纤维化造模方式的选择[J].中国免疫学杂志,2010,26(3):254-257.
[13]CHUA F,GAULDIE J,LAURENT G J.Pulmonary fibrosis:searching for model answers[J].Am J Respir Cell Mol Biol,2005,33(1):9-13.
[14]MOORE B B,HOGABOAM C M.Murine models of pulmonary fibrosis[J].Am J Physiol Lung Cell Mol Physiol,2008,294(2):L152-L160.
[15]蔡珊,陈平.巨噬细胞炎症蛋白与呼吸系统疾病[J].国外医学(呼吸系统分册),2002,22(4):175-177,181.
[16]STRIETER R M,GOMPERTS B N,KEANE M P.The role of CXCchemokines in pulmonary fibrosis[J].J Clin Invest,2007,117(3):549-556.
[17]GAO Q,LI Y,PAN X,et al.Lentivirus expressing soluble ST2 alleviates bleomycin-induced pulmonary fibrosis in mice[J].lnt Immunopharmacol,2016,30:188-193.
[18]TODD N W,LUZINA I G,ATAMAS S P.Molecular and cellular mechanisms of pulmonary fibrosis[J].Fibrogenesis Tissue Repair,2012,5(1):11.