[Abstract ] Objective Silicosis is one of the most serious occupational diseases in China .In this study,we explored the reg -ulatory effect of N-acetyl-seryl-aspartyl-lysyl-proline ( Ac-SDKP ) on angiotensin ( Ang ) Ⅱ-induced extracellular signal-regulated ki-nase ( ERK1/2) and Jun N-terminal kinase ( JNK) signals and its inhibitory effect on the differentiation of human embryonic lung MRC-5 fibroblasts to myofibroblasts via Ang Ⅱ-induced ERK1/2 and JNK signals . Methods Human embryonic lung MRC-5 fibro-blasts were induced by Ang Ⅱand pre-treated with the JNK signal inhibitor ( SP600125 ) , the ERK1/2 signal inhibitor ( PD98059 ) or Ac-SDKP.The proliferation of the cells was measured by MTT assay .The expressions of αS-MA, SRF, p-ERK1/2 and p-JNK were determined by immunocytochemical staining , and the expression levels of these proteins and collagen Ⅰwere detected by Western blot .Results The A value of Ang Ⅱ group (0.56 ±0.08) measured by MMT assay was 2.07 fold as control group ( 0.27 ±0.05 ). Pretreatment with SP600125 , PD98059 and Ac-SDKP, the A value were (0.39 ±0.02), (0.40 ±0.03) and (0.36 ±0 0.5) that had a statistical significance with Ang Ⅱgroup.The up-regulation of colla-gen type Ⅰ,α-SMA, SRF were induced by Ang Ⅱ by 4.50, 3.50 and 3.00 fold compared with control group.Moreover, the expression of p-ERK1/2 and p-JNK were increased as 6.71 and 7.90 fold as control. Pre-treatment with Ac-SDKP could inhibit p-JNK and p-ERK1/2 to 29.79% and 46.84% compared with AngⅡ group. Conclusion Ac -SDKP can inhibit the differentiation of human embryonic lung MRC-5 fibroblasts to myofibroblasts by regulating AngⅡ-induced JNK and ERK1/2 signals.%目的：矽肺是我国最严重的职业病之一。文中研究N-乙酰基-丝氨酰-天门冬氨酰-赖氨酰-脯氨酸（ N-acetyl-ser-yl-aspartyl-lysyl-proline， Ac-SDKP）对血管紧张素（angiotensin， Ang）Ⅱ诱导的细胞外信号调节激酶信号（extracelluler signal-reg-ulated kinase， ERK1／2）信号和Jun氨基末端激酶信号（Jun N-terminal kinase， JNK）的调控，抑制人胚肺MRC-5成纤维细胞向肌成纤维细胞的分化。观察AngⅡ是否经由ERK1／2和JNK信号诱导人胚肺MRC-5成纤维细胞向肌成纤维细胞分化以及Ac-SDKP对此过程的调节作用。方法实验分为5组：对照组（无血清培养基培养）、AngⅡ诱导组（采用100 nmol／L AngⅡ诱导MRC-5细胞）、SP600125干预组（予以 JNK 信号阻断剂 SP600125预处理）、PD98059干预组（ ERK1／2信号阻断剂PD98059预处理）和AcS-DKP干预组（ Ac-SDKP预处理）。 MTT法检测细胞增殖，免疫细胞化学法检测α-平滑肌肌动蛋白（α-smooth muscle actin，α-SMA）及其上游转录因子血清反应因子（serum response factor， SRF）、p-ERK1／2和p-JNK的定位及表达；Western blot法检测Ⅰ型胶原、α-SMA、SRF和p-ERK1／2、p-JNK的表达水平。结果 Ang Ⅱ诱导组A值（0．56±0．08）为对照组（0．27±0．05）的2．07倍；SP600125干预组、PD98059干预组和Ac-SDKP干预组A值分别为（0．39±0．02）、（0．40±0．03）、（0．36±0．05）与AngⅡ诱导组（0．56±0．08）比较，差异均具有统计学意义（P＜0．05）；AngⅡ诱导组的Ⅰ型胶原、α-SMA、SRF蛋白水平明显上调，分别是对照组的4．50、3．50和3．00倍；AngⅡ诱导组能够上调p-JNK和p-ERK1／2的表达，分别是对照组的6．71和7．90倍；而Ac-SDKP干预组能够抑制p-JNK和pE-RK1／2的表达，分别是AngⅡ诱导组的29．79％和46．84％。结论Ac-SDKP能够通过对AngⅡ介导的ERK1／2信号、JNK信号的调节，抑制肺成纤维细胞向肌成纤维细胞的分化。
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