IL-37、Smad3在博来霉素致大鼠肺纤维化模型中的表达及意义

摘要

目的 研究博来霉素致肺纤维化大鼠肺组织中IL-37、Smad3的表达水平,探讨其在PF发生、发展中的作用及意义.方法 将45只清洁级Wistar大鼠按随机数字表法分为健康对照组(N组)、博来霉素组(B组)、地塞米松治疗组(D组),每组大鼠15只,B组及D组大鼠气管内给予博来霉素4mg/kg制作肺纤维化模型,N组给予相同体积生理盐水作为对照组,D组大鼠于肺纤维化造模基础上第2天每日腹腔注射地塞米松3mg/kg,N、B组大鼠腹腔注射生理盐水作为对照.各组大鼠分别于造模后7、14、28天处死,HE染色评价肺组织病理形态学变化,碱水解法及酶联免疫吸附法分别测定肺组织匀浆中羟脯氨酸(HYP)、IL-37含量,RT-PCR法测定肺组织中Smad3 mRNA表达量.结果 (1)HE染色示B、D组大鼠肺组织由肺泡炎逐渐发展为纤维化性变,B、D组HYP含量在各时间点均较N组升高,以28天为著,P＜0.05;(2)B、D组IL-37含量于第7天升高明显,后逐渐降低,但均高于N组,P＜0.05;(3)随着时间延长B、D组肺组织Smad3mRNA表达量逐渐升高,差异有统计学意义(P＜0.05).结论 IL-37、Smad3在大鼠肺纤维化发病过程中起重要作用,可能参与了肺纤维化发生与发展.%Objective To study the expression of IL-37 and Smad3 in lung tissue of rats with bleomycin induced pulmonary fibrosis,and to explore the role and significance of PF in the occurrence and development of pulmonary fibrosis.Methods 45 Sprague Wistar rats were randomly divided into the normal control group (the N group),the bleomycin group (the B group),and the dexamethasone group (the D group),15 rats in each group.The B group and the D group were given intratracheal bleomycin lung 4mg/kg fibrosis model,and the N group was given the same volume of normal saline as the control group.Based on the second day of pulmonary fibrosis model,the group D was injected with dexamethasone 3mg/kg,and the group B and N were intraperitoneally injected with normal saline as control.The rats were sacrificed 7,14 and 28 days after modeling.HE staining was used to evaluate the morphological changes,and hydroxyproline and IL-37 in lung tissue was measured by alkali hydrolysis and enzyme linked immunosorbent assay (HYP).The expression of Smad3mRNA in lung tissue were detected by RT-PCR.Results (1) HE staining showed that the group B and D gradually developed into fibrosis.The level of Hyp at each time point was significantly higher in the group B and D than in the group N (P ＜ 0.05).(2) IL-37 content in the seventh day increased significantly in the group B and D.but it was still higher than that in the group N (P ＜ 0.05).(3) Smad3mrna expression increased gradually in the group B and D (P ＜ 0.05).Conclusion IL-37 and Smad3 play important roles in the pathogenesis of pulmonary fibrosis in rats,and they may be involved in the occurrence and development of pulmonary fibrosis.