中国医科大学学报2025,Vol.54Issue(5):407-413,7.DOI:10.12007/j.issn.0258-4646.2025.05.005
骨髓间充质干细胞调节小胶质细胞极化减轻SNI大鼠神经病理性疼痛
Bone marrow mesenchymal stem cells regulate microglial polarization to alleviate neuropathic pain in SNI rats
摘要
Abstract
Objective To explore the effects and mechanisms of bone marrow mesenchymal stem cells(BMSCs)in regulating microglial polarization on neuropathic pain in rats with sciatic nerve branch-selective injury(SNI).Methods Fifty SD rats were randomly divided into five groups with ten rats in each group;sham group(rats only exposed sciatic nerve without ligation),SNI group(SNI model was estab-lished),BMSCs group[rats were injected with BMSCs(1×106)through the sheath for 3 days after SNI modeling],BMSCs+sh-NC group[rats were intrathecally injected with BMSCs(1×106)and intrathecally injected with knock-down control(adenovirus 2.5×107 IU)for 3 days after SNI modeling],and BMSCs+sh-YY1 group[rats were intrathecally injected with BMSCs(1×106)and intrathecally injected with YY1 knockdown adenovirus(2.5×107 IU)for 3 days after SNI modeling].Neuropathic pain was assessed using paw withdrawal threshold(PWT)and paw withdrawal thermal latency(PWTL)following mechanical stimulation.Immunofluorescence was used to detect the expression of CD86,CD206,iNOS,and Arg1 in the rat spinal cord tissues.Western blotting was used to measure the expression of YY1 and KLF4 in spinal cord tissue.Results Compared with sham group,the values of PWTL and PWT in the SNI group significantly reduced(both P<0.05).In spinal cord tissue,the positive rates of iNOS and CD86 protein increased,whereas the positive rates of CD206 and Arg1 protein and the expression of YY1 and KLF4 decreased(all P<0.05).Compared with the SNI group,the values of PWTL and PWT in the BMSCs and BMSCs+sh-NC groups increased(all P<0.05),the positive rate of CD86 protein in the spinal cord decreased,whereas the positive rate of CD206 protein and the expression of YY1 and KLF4 increased(all P<0.05).Also,the positive rate of iNOS protein in the spinal cord tissue decreased and the positive rate of Arg1 increased in the BMSCs group(all P<0.05).Compared with the BMSCs and BMSCs+sh-NC groups,the PWTL and PWT values in the BMSCs+sh-YY1 group decreased(all P<0.05).The positivity rate of CD86 protein increased,the positivity rate of CD206 protein decreased,and the expression of YY1 and KLF4 decreased in the spinal cord tissue(all P<0.05).Conclusion Intrathecal injection of BMSCs promotes M2 polarization of microglia in the spinal cord and relieves neuropathic pain in rats with SNI,and its mechanism may be related to the upregulation of KLF4 expression mediated by YY1.关键词
骨髓间充质干细胞/神经病理性疼痛/小胶质细胞极化/转录因子阴阳1/Krüppel样因子4Key words
bone marrow mesenchymal stem cell/neuropathic pain/microglial polarization/Yin Yang 1/Krüppel-like factor 4分类
临床医学引用本文复制引用
苗杨,宗宁,何垒,董道松,郭欣欣..骨髓间充质干细胞调节小胶质细胞极化减轻SNI大鼠神经病理性疼痛[J].中国医科大学学报,2025,54(5):407-413,7.基金项目
辽宁省自然科学基金(2019-BS-295) (2019-BS-295)