JNK信号通路通过介导细胞凋亡对肺纤维化的调控作用

Regulation of JNK signaling pathway on pulmonary fibrosis via cellular apoptosis

目的观察肺纤维化中肺组织caspase-3和磷酸化c-Jun氨基末端激酶(p-JNK)蛋白表达的变化,并探讨JNK信号转导通路对肺纤维化的调控作用。方法 72只健康雄性Wistar大鼠随机分为正常对照组(N组)、肺纤维化模型组(M组),肺纤维化+JNK抑制剂干预组(I组),每组24只,分别于第3、7、14、28天处死,每组6只。留取肺组织,对其行苏木素-伊红(HE)染色,观察其病理学改变,碱水解法测定其中羟脯氨酸的含量,免疫组织化学法测肺组织中caspase-3和p-JNK的变化。结果模型组早期肺泡炎症明显,后期肺组织实变,caspase-3和p-JNK蛋白表达含量均显著增加(P<0.05),14d时达峰值。干预组能明显阻断JNK的激活(P<0.05),干预组caspase-3表达较模型组显著减少(P<0.05),14d时减少最明显。结论细胞凋亡是肺纤维化的一个重要病理组织学特点。JNK信号转导通路在肺纤维化中被激活,发挥促细胞凋亡效应。

Objective To investigate the variation in the expression of caspase-3 and phosphorylated c-Jun NH-terminal kinase （p-JNK） of lung tissue, and to determine the regulatory effects of JNK signaling pathway on pulmonary fibrosis. Methods A total of 72 male Wistar rats in healthy condition were randomly assigned into normal control group （group N, n=24）, pulmonary fibrosis model group （group M, n=24） and pulmonary fibrosis treated with JNK inhibitor group （group I, n=24）. Six rats of each group were sentenced on days 3, 7, 14 and 28, respectively. Lung tissues were then extracted for HE staining to determine the pathological changes. The level of hydroxyproline was detected via alkaline hydrolysis, and the variation in caspase-3 and p-JNK in lung tissue was assessed using immunohistochemistry assay. Results Group M developed considerable premature alveolar inflammation followed by pulmonary consolidation. These changes were reflected by a remarkable increase in the expression levels of caspase-3 and p-JNK protein （P〈0.05） that peaked on day 14. Additionally, group I conferred marked blockade of JNK activation （P〈O.05）, as shown by a significant decline in caspase-3 expression （P〈0.05）, and in particular, on day 14. Conclusion As a major histopathological feature of pulmonary fibrosis, cell apoptosis is predisposed via activation of JNK signaling pathway.