Ac-SDKP调控Gαs/Gαi信号抑制大鼠矽肺纤维化的作用  

Ac-SDKP inhibits silicosis fibrosis in rats by regulating Gαs/Gαi signaling

作　　者：刘燕 耿玉聪 徐洪[2] 张丽娟[2] 王建辉 王瑞雪 胡启峰[3] 杨方[2] 

机构地区：[1]华北理工大学基础医学院,河北唐山063000 [2]华北理工大学医学实验中心,河北唐山063000 [3]唐山市第二医院创伤科,河北唐山063000

出　　处：《西安交通大学学报（医学版）》2017年第1期24-28,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.81472953);河北省自然科学基金青年项目(No.H2016209161)~~

摘　　要：目的观察N-乙酰基-丝氨酰-天冬氨酰-赖氨酰-脯氨酸(Ac-SDKP)能否通过调控激动型G蛋白α(Gαs)/抑制型G蛋白α(Gαi)信号对大鼠矽肺纤维化发挥保护作用。方法雄性Wistar大鼠随机分为3组(n=10):对照16周组,矽肺模型16周组,Ac-SDKP预防治疗组。采用HE染色观察肺组织病理形态的改变,Western blot检测α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原(CollagenⅠ)、纤连蛋白(Fn)、Gαs、Gαi2、Gαi3和环磷酸腺苷(cAMP)的含量,采用免疫荧光染色检测矽肺组织α-SMA/Gαi3的共表达。结果在矽肺模型16周组,HE染色显示肺组织内出现多个细胞性结节的融合和间质纤维化的形成,并可见细胞纤维性结节的形成。免疫荧光化学染色显示在纤维化病变区域α-SMA/Gαi3共表达增强。与对照组比较,矽肺模型16周组α-SMA、CollagenⅠ、Fn、Gαi2及Gαi3的蛋白表达明显升高,Gαs和cAMP的表达明显下降;与矽肺模型16周组相比,Ac-SDKP预防治疗组肺组织病理损伤减轻,α-SMA/Gαi3共表达减少,α-SMA、CollagenⅠ、Fn、Gαi2及Gαi3的蛋白表达显著降低,Gαs和cAMP的表达明显升高。结论 Ac-SDKP能够通过调节Gαs、Gαi促进cAMP的生成对矽肺大鼠肺纤维化产生保护作用。Objective To observe whether N-acetyl-seryl-aspartyl-lysyl-proline （Ac-SDKP） can inhibit rat silicotic fibrosis by regulating stimulatory G protein α （Gαs）/ inhibitory G protein α （Gαi） signal. Methods Male Wistar rats were randomly divided into three groups （ n = 10） .- control 16-w group, silicosis 16-w group, and Ac- SDKP pre-treatment group. The pathological changes of the lung tissue was observed by HE staining; the expressions of α-smooth muscle actin （α-SMA）, Collagen I , fibronectin （Fn）, Gαs, Gαi2, Gαi3 and cAMP were detected by Western blot. Immunofluorescence was performed on lung tissue sections to detect the coexpression of α-SMA/Gαi3. Results Within silicosis 16-w group, HE staining showed that the silicotic nodule volume increased, nodule fusion and the formation of interstitial fibrosis could be seen, and cell fibrous nodules were visible. Immunofluorescence staining showed the enhanced coexpression of α-SMA/Gαi3 in fibrosis area. Compared with those in control group, the expressions of α-SMA, Collagen I , Fn, Gαi2 and Gαi3 significantly increased in silicosis 16-w group, but the expressions of Gαs and cAMP decreased. Compared with silicosis 16-w group, Ac-SDKP pre-treatment group had alleviated lung injury and decreased coexpression of α-SMA/Gαi3. The expressions of α-SMA, Collagen I , Fn, Gαi2 and Gαi3 protein significantly decreased in Ac-SDKP pre-treatment group, while the expressions of Gαs and cAMP increased obviously. Conclusion Ac-SDKP can regulate the expressions of Gαs and Gαi and promote the formation of cAMP, thus playing an effective role against silicotic fibrosis.

关 键 词：N-乙酰基-丝氨酰-天冬氨酰-赖氨酰-脯氨酸 矽肺病 环磷酸腺苷 激动型G蛋白α／抑制性G蛋白α 

分 类 号：R363[医药卫生—病理学]