Th1/Th2型细胞因子在小鼠肺纤维化发病中的作用
The effect of Th1 /Th2 type cytokines in pulmonary fibrosis pathogenesis
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摘要: 目的:了解Th1/Th2型细胞因子在小鼠肺纤维化中的作用。方法:雄性昆明小鼠40只,随机分为3组。对照组8只小鼠气管内注入0. 9%氯化钠注射液,第7天将小鼠一次性处死;模型组16只小鼠气管内注入博来霉素;干预组16只在造模次日给予干扰素腹腔注射,卡托普利胃管内注入,在注药后第3、7、14、28天各处死4只,分别取支气管肺泡灌洗液(BALF),ELISA法检测BALF中白介素(IL)-4、IL-12水平;取对照组和模型组小鼠右肺标本,病理半定量分析肺泡炎程度。结果:与对照组比较,模型组BALF中IL-12水平显著降低(P0. 01),IL-4水平明显升高(P0. 01),呈Th2相对优势表达;与模型组比较,干预组BALF中IL-12水平升高(P0. 01),IL-4水平降低(P0. 01),部分恢复Th1/Th2的动态平衡;与模型组比较,干预组小鼠第3、7天肺泡炎程度较相应的模型组差异均无统计学意义(0. 05),第28天肺泡炎明显减轻(P0. 01)。结论:Th1/Th2型细胞因子平衡失调是博来霉素所致肺纤维化的发病机制之一;干扰素联合卡托普利可以部分恢复Th1/Th2型细胞因子平衡失调,减轻后期肺泡炎和肺纤维化的形成。Abstract: Objective: To observe the effect of Th1 /Th2 type cytokines in pulmonary fibrosis pathogenesis. Methods: Forty male Kunming mice were randomly divided into 3 groups，8 mice in control group were intratracheal injection with saline， and executed on the 7th day; 16 mice in model group were intratracheal injection with bleomycin. Sixteen mice in treatment group were intraperitoneal injection with interferon- and captopril by oral gavage on the day after model-building，4 mice were executed once on the 3rd，7th， 14th and 28th day. Bronchus alveolus lavage fluid( BALF) was collected， the levels of interleukin( IL-4) and IL-12 in BALF were detected by ELISA method. The right lung specimen was collected in control and model groups，and pathological semi-quantitative analysis of alveolitis degree was detected. Results: Compared with control group， IL-12 level in BALF in model group was reduced( P ＜ 0. 01) ; IL-4 level was increased( P ＜ 0. 01) ，Th2 dominant expression was expressed. Compared with model group， IL-12 level in BALF in treatment group was increased( P ＜ 0. 01) ; IL-4 level was reduced( P ＜ 0. 01) ，partly recovered to the dynamic balance of Th1 /Th2. Compared with model group， there was no difference on alveolus inflammation in treatment group at early stage ( 3rd，7th day) ， the degree of alveolus inflammation fibrosis was reduced obviously at later stage( 28th day ) ( P ＜ 0. 01) . Conclusions: Th1 /Th2 cytokine balance disorder is one of mechanism of bleomycin-leading pulmonary fibrosis; combined with interferon- and captopril may partly restore Th1 /Th2 cytokine balance， and lighten the alveolitis ＆ pulmonary fibrosis at the later stage.
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Key words:
- pulmonary fibrosis /
- interleukin /
- interferon- /
- bleomycin /
- captopril /
- alveolitis /
- mice
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