信号转导和转录激活因子3调控音猬因子信号途径对脑出血引发神经损伤的影响  

Signal transducer and activator of transcription 3 influences nerve injury caused by intracerebral hemorrhage by regulating the sonic hedgehog signal pathway

作　　者：刘蔚然 王辉 董晓柳[1] 张秀清[1] 宋丽华[1] 高铭 LIU Weiran;WANG Hui;DONG Xiaoliu;ZHANG Xiuqing;SONG Lihua;GAO Ming(Department of Neurorehabilitation,Tangshan People’s Hospital,Tangshan,Hebei 063000,China;Department of Neurology,Tangshan Kaiping District Hospital,Tangshan,Hebei 063000,China)

机构地区：[1]唐山市人民医院神经康复科,河北唐山063000 [2]唐山市开平区医院神经内科,河北唐山063000

出　　处：《国际神经病学神经外科学杂志》2025年第1期8-14,共7页Journal of International Neurology and Neurosurgery

基　　金：唐山市卫生健康委医学科学研究课题(20211512)。

摘　　要：目的探究信号转导和转录激活因子3(STAT3)调控音猬因子(Shh)信号途径对脑出血(ICH)引起神经细胞损伤的影响。方法将大鼠神经元PC12细胞分为对照组和ICH模型组,通过qRT-PCR和蛋白质印迹检测两组细胞中STAT3和Shh的mRNA和蛋白质表达水平,MTT分析两组细胞的增殖曲线,流式细胞术检测细胞的凋亡率。将BALB/c小鼠随机分为假手术组、ICH模型组、ICH+PBS组与ICH+Stattic组,通过HE染色评估各组小鼠脑损伤情况。使用干扰RNA技术敲降ICH模型组PC12细胞,分组为对照组、ICH模型组、ICH+shRNA阴性对照组、ICH+sh-STAT3组,并为证实STAT3对Shh的调控作用,同时敲降STAT3和Shh,设置ICH+sh-STAT3+sh-Shh组。此外,通过转染过表达载体增加ICH模型组PC12细胞中Shh的表达,分组为对照组、ICH模型组、ICH+空白载体对照组、ICH+Shh过表达组。采用MTT和流式细胞术检测以上各组增殖曲线和凋亡变化。结果在ICH模型组PC12细胞和ICH模型组小鼠脑组织中STAT3 mRNA和蛋白质表达水平增加(P<0.05),而Shh表达减少(P<0.05)。敲降STAT3减轻了ICH小鼠的脑损伤。敲降STAT3后,ICH模型中Shh信号相关蛋白(Shh,SMO和Gli-1)表达增加(P<0.05),ICH模型组PC12细胞的增殖增加(P<0.05),细胞凋亡率减少(P<0.05)。过表达Shh后促进ICH模型中PC12细胞的增殖(P<0.05),并且减少了细胞凋亡(P<0.05)。结论STAT3调控Shh信号途径影响ICH细胞模型中PC12细胞的增殖和凋亡水平。Objective To investigate the influence of signal transducer and activator of transcription 3(STAT3)on neural cell injury caused by intracerebral hemorrhage(ICH)by regulating the sonic hedgehog(Shh)signaling pathway.Methods Rat neuron PC12 cells were divided into control group and ICH model group,and qRT-PCR and Western blot were used to measure the mRNA and protein expression levels of STAT3 and Shh.MTT assay was used to analyze the proliferation curve of cells in the two groups,and flow cytometry was used to measure cell apoptosis rate.BALB/c mice were randomly divided into sham-operation group,ICH model group,ICH+PBS group,and ICH+Stattic group.HE staining was used to assess brain injury in each group of mice.PC12 cells in the ICH model group were subjected to knockdown using RNA interference technology and divided into the following groups:control group,ICH model group,ICH+shRNA negative control group,and ICH+sh-STAT3 group.To confirm the regulatory role of STAT3 on Shh,both STAT3 and Shh were knocked down,and the ICH+sh-STAT3+sh-Shh group was established.Additionally,Shh expression was enhanced in ICH model PC12 cells by transfection with overexpression vectors,with the groups categorized as:control group,ICH model group,ICH+empty vector control group,and ICH+Shh overexpression group.Proliferation curves and apoptosis changes in these groups were analyzed using the MTT assay and flow cytometry.Results STAT3 mRNA and protein expression levels were elevated(P<0.05),while Shh expression was reduced(P<0.05)in ICH model PC12 cells and mouse brain tissues.Knockdown of STAT3 alleviated brain injury in ICH model mice.Silencing STAT3 increased the expression of Shh signaling-related proteins(Shh,SMO,and Gli-1)(P<0.05),enhanced proliferation(P<0.05),and reduced apoptosis(P<0.05)in ICH model PC12 cells.Overexpression of Shh promoted proliferation(P<0.05)and decreased apoptosis(P<0.05)in ICH model cells.Conclusions STAT3 influences the proliferation and apoptosis of PC12 cells in ICH cell model by regulating the Shh sign

关 键 词：脑出血 信号转导和转录激活因子3 Shh信号途径 神经损伤 细胞凋亡 

分 类 号：R743[医药卫生—神经病学与精神病学]