摘要
目的观察木犀草素通过酪氨酸激酶2/信号转导及转录激活因子3(JAK2/STAT3)信号通路对增生性瘢痕成纤维细胞(HSF)增殖、凋亡和迁移的影响。方法从人增生性瘢痕组织中提取HSF,经过分离培养后将HSF细胞分为对照组、木犀草素低剂量组、木犀草素高剂量组、木犀草素高剂量组+Colivelin组(JAK2/STAT3激活剂)、AG490组(JAK2/STAT3信号通路抑制剂)。MTT检测细胞增殖,Transwell实验检测细胞迁移和侵袭,流式细胞术检测细胞凋亡,实时荧光定量聚合酶链式反应(qRT-PCR)检测细胞JAK2、STAT3 mRNA表达,蛋白免疫印迹(Western blot)法检测Ⅰ型胶原蛋白(Col-Ⅰ)、Col-Ⅲ、α-平滑肌肌动蛋白(α-SMA)、Ki-67、半胱氨酸天冬氨酸蛋白酶3(Caspase-3)、p-JAK2、JAK2、p-STAT3、STAT3蛋白表达。结果与对照组比较,木犀草素低剂量组、木犀草素高剂量组和AG490组HSF细胞增殖率、细胞迁移个数和侵袭个数、JAK2 mRNA、STAT3 mRNA、Col-Ⅰ、Col-Ⅲ、α-SMA、Ki-67、p-JAK2/JAK2、p-STAT3/STAT3水平均显著降低(P<0.05),细胞凋亡率、Caspase-3蛋白表达均显著升高(P<0.05);Colivelin可部分逆转木犀草素对HSF的抑制作用(P<0.05);AG490组HSF各项检测指标与木犀草素高剂量组处于同一水平(P>0.05)。结论木犀草素可抑制HSF增殖、迁移,促进其凋亡,可能是通过抑制JAK2/STAT3信号通路实现。
Objective To investigate whether luteolin modulates proliferation,apoptosis,and migration of human hypertrophic scar fibroblasts(HSF)through the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway.Methods HSF were isolated from human hypertrophic scar tissue and cultured in vitro.Cells were allocated to the following groups:Control,luteolin low dose,luteolin high dose,luteolin high dose+Colivelin(a JAK2/STAT3 activator),and AG490(a JAK2/STAT3 pathway inhibitor).Cell proliferation was assessed by MTT assay;migration and invasion by Transwell assays;apoptosis by flow cytometry;JAK2 and STAT3 mRNA levels by real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR);and protein expression of type I collagen(Col-I),Col-III,alpha-smooth muscle actin(α-SMA),Ki-67,caspase-3,p-JAK2,JAK2,p-STAT3,and STAT3 by Western blot.Results Relative to the Control group,luteolin low-dose,luteolin high-dose,and AG490 treatments significantly reduced HSF proliferation rate,numbers of migrating and invading cells,JAK2 and STAT3 mRNA,Col-I,Col-III,α-SMA,Ki-67,and the phosphorylation ratios p-JAK2/JAK2 and p-STAT3/STAT3(P<0.05).Apoptosis rate and caspase-3 protein expression were significantly increased in these groups(P<0.05).Colivelin partially reversed luteolin's inhibitory effects on HSF(P<0.05).No significant differences were observed between the AG490 group and the luteolin high-dose group(P>0.05).Conclusion Luteolin suppresses proliferation and migration and promotes apoptosis of HSF.These effects are likely mediated,at least in part,by inhibition of the JAK2/STAT3 signaling pathway.
作者
郭强
殷河慧
朱旭东
GUO Qiang;YIN Hehui;ZHU Xudong(Department of Dermatology,966th Hospital of the Joint Logistics Support Force of the People's Liberation Army of China,Dandong,Liaoning 118000)
出处
《河北中医》
2026年第4期608-613,共6页
Hebei Journal of Traditional Chinese Medicine
