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他莫昔芬通过调节大鼠的AKT通路抑制成纤维细胞增殖并预防硬膜外纤维化。

Tamoxifen inhibits fibroblast proliferation and prevents epidural fibrosis by regulating the AKT pathway in rats.

作者信息

Wang Shuguang, Li Xiaolei, Yan Lianqi, Nie Qian, Dai Jihang, Chen Hui, Wang Jingcheng, Sun Yu

机构信息

Department of Orthopedics, Orthopedic Institute, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou, 225001, China.

Department of Orthopedics, Orthopedic Institute, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou, 225001, China.

出版信息

Biochem Biophys Res Commun. 2018 Mar 18;497(4):937-942. doi: 10.1016/j.bbrc.2018.01.032. Epub 2018 Jan 6.

Abstract

Many factors contribute to epidural fibrosis after lumbar laminectomy, particularly the excessive proliferation of fibroblasts. Many studies have shown that tamoxifen (TAM) inhibits fibroblast proliferation and reduces fibrosis, but the detailed effect and mechanism of TAM on preventing epidural fibrosis are unknown. To investigate the effect of TAM on fibroblast proliferation and epidural fibrosis, fibroblasts were cultured and treated with different concentrations of TAM. Cell Counting Kit-8(CCK-8) detection, cell cycle analysis and western blot analysis were used to detect the roles of TAM in regulating fibroblast proliferation. Lumbar laminectomies were performed in rats, and various concentrations of TAM were administered by gavage. Histological and immunohistochemical analyses were used to evaluate the effects of TAM on preventing epidural fibrosis. CCK-8 detection showed that TAM could inhibit fibroblast viability; western blot analysis showed that TAM could decrease the expression of proliferative proteins p-AKT and cyclinD1 and increase the expression of antiproliferative proteins P21 and P27. Histological analysis showed that TAM could reduce epidural fibrosis. Immunohistochemical analysis showed that the p-ATK expression in epidural scar tissue was decreased after TAM treatment. The present study demonstrated that TAM could inhibit fibroblast proliferation and prevent epidural fibrosis, potentially through the regulation of the AKT pathway.

摘要

腰椎板切除术后硬膜外纤维化受多种因素影响,尤其是成纤维细胞的过度增殖。许多研究表明,他莫昔芬(TAM)可抑制成纤维细胞增殖并减少纤维化,但TAM预防硬膜外纤维化的具体作用及机制尚不清楚。为研究TAM对成纤维细胞增殖及硬膜外纤维化的影响,培养成纤维细胞并用不同浓度的TAM进行处理。采用细胞计数试剂盒-8(CCK-8)检测、细胞周期分析及蛋白质免疫印迹分析来检测TAM在调节成纤维细胞增殖中的作用。对大鼠进行腰椎板切除术,并通过灌胃给予不同浓度的TAM。采用组织学和免疫组织化学分析来评估TAM预防硬膜外纤维化的效果。CCK-8检测显示TAM可抑制成纤维细胞活力;蛋白质免疫印迹分析显示TAM可降低增殖蛋白p-AKT和细胞周期蛋白D1的表达,并增加抗增殖蛋白P21和P27的表达。组织学分析显示TAM可减轻硬膜外纤维化。免疫组织化学分析显示TAM处理后硬膜外瘢痕组织中p-ATK表达降低。本研究表明,TAM可能通过调节AKT通路抑制成纤维细胞增殖并预防硬膜外纤维化。

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