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作 者:王玲姝[1] 张宇[2] 李冠男 李孟[3] WANG Lingshu;ZHANG Yu;LI Guannan;LI Meng(First Affiliated Hospital,Heilongjiang University of Chinese Medicine,Harbin 150040,China;Heilongjiang University of Chinese Medicine,Harbin 150040,China;College of Pharmacy,Heilongjiang University of Chinese Medicine,Harbin 150040,China)
机构地区:[1]黑龙江中医药大学附属第一医院,哈尔滨150040 [2]黑龙江中医药大学,哈尔滨150040 [3]黑龙江中医药大学药学院,哈尔滨150040
出 处:《上海针灸杂志》2022年第11期1133-1138,共6页Shanghai Journal of Acupuncture and Moxibustion
基 金:国家自然科学基金项目(81373839);黑龙江中医药大学研究生创新科研项目(2020yjscx035);黑龙江中医药大学科研基金项目(2019MS04)。
摘 要:目的观察火针对坐骨神经损伤大鼠运动功能及脂肪酸合酶基因启动子区H3K27乙酰化(H3K27ac)水平的影响,探讨脂肪酸合酶(FASN)基因启动子区H3K27ac参与火针促进坐骨神经功能恢复中表观遗传的调控机制。方法将72只大鼠随机分为假手术组、模型组和火针组,每组24只。火针组与模型组建立坐骨神经压榨损伤大鼠模型,火针组给予火针治疗。采用坐骨神经功能指数(SFI)评价各组大鼠的运动功能,免疫组化法检测坐骨神经损伤处FASN的表达,Western blot法检测组蛋白去乙酰化酶1(HDAC1)的表达,染色质免疫共沉淀法检测FASN基因启动子区H3K27ac水平。结果与假手术组比较,模型组SFI评分、FASN蛋白表达显著下降(P<0.01);HDAC1蛋白表达、FASN基因启动子区H3K27ac丰度显著升高(P<0.01)。与模型组比较,火针组SFI评分、FASN蛋白表达、FASN基因启动子区H3K27ac丰度显著升高(P<0.01);HDAC1蛋白表达显著降低(P<0.01)。结论火针能够有效改善坐骨神经损伤模型大鼠的运动功能,其机制可能与抑制坐骨神经损伤组织中HDAC1表达,促进FASN基因启动子区H3K27乙酰化有关。Objective To observe the effects of fire needling on the motor function and H3K27 acetylation(H3K27ac)level in thepromoter region of fatty acid synthase(FASN)gene and discuss the epigenetic regulation mechanism of H3K27ac in the promoter region of FASN gene in fire-needle acupuncture promoting the recovery of sciatic function.Method Seventy-two rats were randomly divided into a sham operation group,a model group,and a fire needle group,with 24 rats in each group.Rat models of constrictive sciatic injury were established in the fire needle and model groups.The fire needle group was intervened by fire needling.The sciatic functional index(SFI)was adopted to evaluate rat’s motor function,the expression of FASN in the injured area of sciatic was determined by immunohistochemical method,Western blot was used to detect the expression of histone deacetylase 1(HDAC1),chromatin immunoprecipitation was employed to measure the H3K27ac level in the promoter region of FCSN gene.Result Compared with the sham operation group,the SFI score and FASN protein expression level dropped significantly in the model group(P<0.01),and the HDAC1 protein expression level and the H3K27ac abundance in the promoter region of FASN increased notably(P<0.01).Compared with the model group,the SFI score,FASN protein expression,and H3K27ac abundance in the promoter region of FASN increased significantly in the fire needle group(P<0.01),and the HDAC1 protein expression declined notably(P<0.01).Conclusion Fire needling can effectively improve motor function in sciatic injury rat models,and the mechanism may be related to inhibiting the HDAC1 expression in the damaged nerve area and encouraging H3K27ac in the promoter region of the FASN gene.
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