层黏连蛋白受体1单克隆抗体抑制博莱霉素诱导的大鼠肺纤维化

Monoclonal antibody against laminin receptor 1 inhibits the pulmonary fibrosis induced by bleomycin in rats

目的研究层黏连蛋白受体1(LAMR1)单克隆抗体(mAb)干预博莱霉素诱导的大鼠肺纤维化。方法雄性SD大鼠72只,随机分为LAMR1 mAb组(L)、对照组(C)和模型组(M)3组,气管内滴入博莱霉素(5 mg/kg体质量)制备肺纤维化模型。3组分别给予LAMR1 mAb、地塞米松、生理盐水3次/周,腹腔注射,于第7、14、28天处死8只大鼠。HE染色观察肺纤维化程度;免疫组化方法检测肺组织中表面活性物质A(SP-A)的含量;ELISA测定血清中羟脯氨酸(Hyp)的含量;PCR方法检测肺组织中基质金属蛋白酶9(MMP-9)及转化生长因子β1(TGF-β1)mRNA的含量。结果各时间段,M组肺纤维化程度及Hyp含量均高于C组和L组,SP-A的含量均低于其余两组,M组肺组织的MMP-9和TGF-β1的mRNA的含量明显高于其余两组。结论 LAMR1 mAb可明显减轻博莱霉素诱导的肺纤维化程度。

Objective To investigate the effect of the anti-laminin receptor 1 （anti-LAMRl） monoclonal antibody （mAb） on rat pulmonary fibrosis induced by bleomycin. Methods Seventy-two male Wistar rats were randomly divided into 3 groups： LAMR1 mAb group （group L）, control group （group C） and model group （group M）. All rats were injected with bleomycin via tracheal instillation （5 mg/kg body mass） to induce pulmonary fibrosis. Then, the rats were treated with anti- LAMR1 mAb （group L）, dexamethasone （group C）, normal saline （group M）, three times each week via intraperitoneal in- jection. Eight rats in each group were sacrificed at the 7, 14, 28 days. Histological changes of the lungs were evaluated by HE staining. The expression of surfactant protein A （SP-A） in the lung tissue was measured by immunohistochemistry. The expression of hydroxyproline （Hyp） in serum was measured by ELISA. The expressions of MMP-9 and TGF-β1 mRNA were evaluated by PCR. Results Compared with the other two groups, group M presented more apparent alveolitis and the higher expression of hydroxyproline in serum, the lower expression of SP-A, and the higher expressions of MMP-9 and TGF-β1 mR- NA in the lung tissue. Conclusion LAMRI mAb can evidently alleviate pulmonary fibrosis induced by bleomycin in rats.