目的 观察肺纤维化大鼠中磷酸化c-jun氨基末端激酶(p-JNK)蛋白和α-平滑肌肌动蛋白(α-SMA)的表达,进一步分析JNK信号通路在该病理生理过程中的作用.方法 将54只健康雄性Wistar大鼠随机分为对照组、模型组和SP600125组.气管内注入博莱霉素制备肺纤维化模型,于造模当日起,各组给予相应药物,分别于第7、14、28 天处死大鼠,取肺组织行苏木素-伊红(HE)染色,光镜下观察大鼠肺组织病理学变化;碱水解法检测肺组织羟脯氨酸(Hyp)含量;应用免疫组织化学法检测肺组织中p-JNK和α-SMA的蛋白表达水平.结果 模型组第7天肺泡炎程度最严重,于第28天形成显著肺纤维化,Hyp含量于第28天达高峰,其p-JNK、α-SMA的含量与对照组比较均明显升高;SP600125组各时间点肺泡炎和纤维化程度低于模型组,且Hyp、p-JNK、α-SMA的含量亦低于模型组;模型组α-SMA与p-JNK蛋白含量呈显著正相关.结论 肺纤维化病理过程可能与p-JNK表达增加并活化α-SMA的表达有关,应用SP600125对肺纤维化有抑制作用.%Objective To determine the expression of phosphorylated c-jun amino acid terminal kinase (p-JNK) protein and a-smooth muscle actin (a-SMA) in rats with pulmonary fibrosis, and to further explore the role that JNK signaling pathway plays in the pathogenesis. Methods Fifty-four healthy male Wistar rats were randomly assigned to control group, model group and SP600125 group. The pulmonary fibrosis models were prepared via intratracheal injection of bleomycin on the initial day. Rats were randomly sacrificed on days 7, 14 and 28. Pathological changes under light microscope were examined after extracting the lung tissues followed by HE staining. The level of hydroxypro-line in the lung tissue was detected applying alkaline hydrolysis technique, and expression levels of p-JNK and a-SMA were tested via immunohistochemical assay. Results In model group, alveolitis was most serious on day 7 and a marked pulmonary fibrosis formed on day 28. The level of hydroxyproline also peaked on day 28, and the contents of p-JNK and a-SMA were significantly higher than those in control group. The SP600125 group showed milder alveolitis and fibrosis at all time points, and the levels of hydroxyproline, p-JNK and a-SMA were remarkably lowered as compared with model group. In addition, there was a marked positive correlation between p-JNK protein and a-SMA in model group. Conclusion The pathogenesis of pulmonary fibrosis may be associated with expression of p-JNK and activation of a-SMA. SP600125 is capable of inhibiting pulmonary fibrosis.
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