A型肉毒毒素对增生性瘢痕JNK信号通路和成纤维细胞相关蛋白表达的影响  

Effects of botulinum toxin type A on the expression of JNK signaling pathway and fibroblast-related proteins in hypertrophic scars

作　　者：郭彩茹 李明鸣 牛宇杰 GUO Cai-ru;LI Ming-ming;NIU Yu-jie(Luoyang Central Hospital Affiliated to Zhengzhou University,Henan International Joint Laboratory of Tumor Immunity and Regenerative Medicine,Henan Province,471000,China;Luoyang Central Hospital Affiliated to Zhengzhou University Burn Plastic Surgery,Henan Province,471000,China)

机构地区：[1]郑州大学附属洛阳中心医院河南省肿瘤免疫与再生医学国际联合实验室,河南洛阳471000 [2]郑州大学附属洛阳中心医院烧伤整形科,河南洛阳471000

出　　处：《中国医疗美容》2022年第3期40-44,共5页China Medical Cosmetology

基　　金：河南省医学科技攻关计划项目:LHGJ20200867。

摘　　要：目的增生性瘢痕是一种真皮纤维增生性疾病。A型肉毒毒素具有预防增生性瘢痕形成的作用,但其抗皮肤纤维化的作用及其机制尚不清楚。本研究分析A型肉毒毒素(BTXA)对增生性瘢痕(HS)JNK信号通路和成纤维细胞相关蛋白表达的影响。方法本研究采用0、1、2、4U/ml BTXA对人瘢痕成纤维细胞进行干预,通过CCK8划痕法、荧光定量PCR和western印迹法检测不同浓度BTXA对HS成纤维细胞增殖、迁移、细胞凋亡和蛋白表达的变化。并对比BTXA干预前后转化生长因子-β1(TGF-β1)、α-肌动蛋白(α-SMA)、结缔组织生长因子(CTGF)、c-Jun氨基末端激酶(JNK)信号通路、磷酸化氨基末端激酶(p-JNK)等成纤维细胞相关蛋白表达的变化。结果与无BTXA干预相比,1、2、4U/ml BTXA干预后HS成纤维细胞增殖能力较低(P<0.05);与无BTXA干预相比,1、2、4U/ml BTXA干预后HS成纤维细胞凋亡率增高(P<0.05);与BTXA干预前相比,BTXA干预后TGF-β1、α-SMA、CTGF等基因水平和蛋白水平均降低(P<0.05);与JNK选择性抑制SP600125干预前相比,JNK选择性抑制SP600125干预后p-JNK表达较高(P<0.05)。结论BTXA可影响HS患者成纤维细胞增殖、迁移和凋亡,并能通过JNK信号通路诱导成纤维细胞凋亡,调控其相关蛋白表达,为临床治疗提供新靶点。Objective To analyze the effects of botulinum toxin type A(BTXA)on the expression of JNK signaling pathway and fibroblast-related proteins in hypertrophic scars(HS).Methods A total of 24 surgical specimens of HS patients in our hospital from November 2020 to June 2021 were selected.BTXA concentrations of 0.2,0.4 and 0.8u/ml were intervened in 8 cases respectively.All patients were tested before BTXA intervention and after 0.2,0.4 and 0.8u/ml BTXA intervention.The effects of different concentrations of BTXA on the viability,proliferation cycle and apoptosis rate of HS fibroblasts were analyzed.The expression of fibroblast-related proteins(TGF-β1)and the changes of JNK signaling pathway(p-JNK)before and after BTXA intervention were compared.Results Compared with no BTXA intervention,the viability of HS fibroblasts was lower than that after 0.2,0.4 and 0.8u/ml BTXA intervention(P<0.05).Compared with no BTXA intervention,0.2,0.4,0.8 U/ml BTXA intervention could increase the number of cells in G1 phase and decrease the number of cells in S and G2 phases(P<0.05).Compared with no BTXA intervention,0.2,0.4,0.8 U/ml BTXA intervention could increase the apoptosis rate of HS fibroblasts(P<0.05).Compared with before BTXA intervention,TGF-β1 expression was lower after BTXA intervention(P<0.05).Compared with JNK selective inhibition of SP600125 before intervention,the expression of p-JNK was higher after JNK selective inhibition of SP600125(P<0.05).Conclusions BTXA can affect the fibroblast activity and cell proliferation cycle of HS patients,and can induce fibroblast apoptosis through the JNK signaling pathway,regulate the expression of related proteins,and provide a new target for clinical treatment.

关 键 词：增生性瘢痕 A型肉毒毒素 JNK信号通路 成纤维细胞蛋白 细胞增生周期 细胞凋亡率 

分 类 号：R622[医药卫生—整形外科]