Wei Zhong-qiu, Yu Wan-ying, Feng Hai-li, Ma Wen-dong, Li Zhi-guo, Xu Hong, Wang Rui-min, Yang Fang
Department of Pathology, Hebei United University, Tangshan 063000, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2013 May;31(5):335-40.
To investigate the regulatory effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on the activation of c-jun N-terminal kinase (JNK) signal transduction pathway and its role in silicotic fibrosis.
A rat model of silicosis was developed by intratracheal instillation. Sixty rats were randomly divided into 4-week control group (n = 10), 8-week control group (n = 10), 4-week silicosis model group (n = 10), 8-week silicosis model group (n = 10), AcSDKP treatment group (n = 10), and AcSDKP prevention group (n = 10). The content of hydroxyproline in lung tissue was measured using a p-dimethylaminoben-zaldehyde reagent; the expression levels of transforming growth factor (TGF)-beta 1 (TGF-β1), phospho-JNK, JNK, and c-jun in lung tissue were measured by Western blot. The lung fibroblasts from neonatal rats were cultured, and the 4th generation of cells were used in the experiment; these cells were divided into control group, TGF-β1 stimulation group, SP600125 intervention group, and AcSDKP intervention group. The distributions of phospho-JNK and c-jun in lung fibroblasts were observed by immunocytochemistry; the expression levels of type I collagen and type III collagen in lung fibroblasts were measured by Western blot.
The expression levels of TGF-β1, phospho-JNK, and c-jun and the content of hydroxyproline in the AcSDKP treatment group were 70.60%, 78.03%, 79.85%, and 71.28%, respectively, of those in the 4-week silicosis model group (P < 0.05) and 77.99%, 66.73%, 69.94%, and 64.82%, respectively, of those in the 8-week silicosis model group (P < 0.05); the expression levels of TGF-β1, phospho-JNK, and c-jun and the content of hydroxyproline in the AcSDKP prevention group were 84.56%, 61.18%, 64.73%, and 74.96%, respectively, of those in the 8-week silicosis model group (P < 0.05). The expression levels of phospho-JNK and c-jun in the AcSDKP intervention group were 54.59% and 55.56%, respectively, of those in the TGF-β1 stimulation group; the expression levels of type I collagen and type III collagen in the AcSDKP intervention group were 79.9% and 84.4%, respectively, of those in the TGF-β1 stimulation group (P < 0.05).
AcSDKP exerts anti-silicotic fibrosis effect probably by inhibiting the activation of JNK signal transduction pathway mediated by TGF-β1 and the deposition of interstitial collagen.
探讨N-乙酰丝氨酰-天冬氨酰-赖氨酰-脯氨酸（AcSDKP）对c-jun氨基末端激酶（JNK）信号转导通路激活的调控作用及其在矽肺纤维化中的作用。
通过气管内滴注建立大鼠矽肺模型。60只大鼠随机分为4周对照组（n = 10）、8周对照组（n = 10）、4周矽肺模型组（n = 10）、8周矽肺模型组（n = 10）、AcSDKP治疗组（n = 10）和AcSDKP预防组（n = 10）。采用对二甲氨基苯甲醛试剂测定肺组织中羟脯氨酸含量；通过蛋白质免疫印迹法检测肺组织中转化生长因子（TGF）-β1、磷酸化JNK、JNK和c-jun的表达水平。培养新生大鼠肺成纤维细胞，取第4代细胞用于实验；将这些细胞分为对照组、TGF-β1刺激组、SP600125干预组和AcSDKP干预组。通过免疫细胞化学观察肺成纤维细胞中磷酸化JNK和c-jun的分布；采用蛋白质免疫印迹法检测肺成纤维细胞中Ⅰ型胶原和Ⅲ型胶原的表达水平。
AcSDKP治疗组中TGF-β1、磷酸化JNK和c-jun的表达水平以及羟脯氨酸含量分别为4周矽肺模型组的70.60%、78.03%、79.85%和71.28%（P < 0.05），8周矽肺模型组的77.99%、66.73%、69.94%和64.82%（P < 0.05）；AcSDKP预防组中TGF-β1、磷酸化JNK和c-jun的表达水平以及羟脯氨酸含量分别为8周矽肺模型组的84.56%、61.18%、64.73%和74.96%（P < 0.05）。AcSDKP干预组中磷酸化JNK和c-jun的表达水平分别为TGF-β1刺激组的54.59%和55.56%；AcSDKP干预组中Ⅰ型胶原和Ⅲ型胶原的表达水平分别为TGF-β1刺激组的79.9%和84.4%（P < 0.05）。
AcSDKP可能通过抑制TGF-β1介导的JNK信号转导通路激活和间质胶原沉积发挥抗矽肺纤维化作用。
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