IL-37抑制IL-18在大鼠肺纤维化模型中的表达及意义的探讨

Expression and significance discussion of IL-37 inhibits IL-18 in rat pulmonary fibrosis models

目的:初步研究博来霉素致肺纤维化大鼠肺组织中IL-37、IL-18的表达水平,探讨其在PF发生、发展中的表达及意义。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),每组大鼠各15只,B组及D组大鼠给予气管内注射博来霉素4 mg/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,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3 mg/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第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IL-18mRNA表达量。结果:(1)HE染色显示B、D组大鼠肺组织病理学改变由肺泡炎症逐渐发展为纤维化,B、D组HYP含量随时间推移逐渐升高,以第28天为著(P<0.05);(2)B、D组IL-37、IL-18mRNA表达于第7天升高至最高点,后逐渐降低,至第28天均高于N组,差异有统计学意义(P<0.05);(3)D组IL-37、IL-18mRNA表达在同一时间均低于B组(P<0.05)。结论:IL-37、IL-18在大鼠肺纤维化发病早期起重要作用,可能参与了肺纤维化发生与发展。

Objective： To investigate the expression of IL-37 and IL-18 in the lung tissue of rats with bleomycin induced pulmonary fibrosis,and to explore the expression and significance of PF in the lung. Methods： 45 Sprague Wistar rats were randomly divided into normal control group（ N Group）,bleomycin group（ B group）,dexamethasone group（ D group）,15 rats in each group. B group and D group rats were given intratracheal injection of bleomycin 4 mg/kg,pulmonary fibrosis model was made,N group was given the same volume of normal saline as control group D,rats in pulmonary fibrosis model based on second days of daily intraperitoneal injection of dexamethasone 3 mg/kg; N,B group rats were intraperitoneally injected with normal saline as control. The rats were sacrificed after modeling 7,14,28 days,HE staining was used to evaluate the lung tissue pathological changes; hydroxyproline in lung tissue was measured by alkali hydrolysis and enzyme linked immunosorbent assay（ HYP）,the content of IL-37,the determination of expression of IL-18 mRNA in lung tissue by RT-PCR. Results：（1） HE staining showed that B,D group of rat lung tissue pathological changes by alveolar inflammation gradually developed into liver fibrosis; B,D group HYP content increased gradually with the elapse of time,for 28 days（ P〈0. 05）.（2）B,D group IL-37,the expression of IL-18 mRNA on the seventh day increased to the highest point. After gradually reduced,to 28 days were higher than N group,the difference was statistically significant（ P〈0. 05）.（3）The expression of IL-37 and IL-18 mRNA in group D was lower than that in group B at the same time（ P〈0. 05）. Conclusion： IL-37,IL-18 play an important role in the early stage of pulmonary fibrosis in rats,and may be involved in the occurrence and development of pulmonary fibrosis.