首页|麝香酮调控BDNF/NF-κB信号通路对多发性抽动症大鼠行为学和神经炎症的影响

麝香酮调控BDNF/NF-κB信号通路对多发性抽动症大鼠行为学和神经炎症的影响

Effect of Muscone on Behavior and Neuroinflammation in Rats with Tourette Syndrome by Regulating BDNF/NF-κB Signaling Pathway

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目的 研究麝香酮对多发性抽动症(Tourette syndrome,TS)大鼠行为学和神经炎症的影响,并分析相关作用机制.方法 60只大鼠随机分为对照组(Control组)、模型组(TS组)、麝香酮低剂量组(L-Mus组)、麝香酮高剂量组(H-Mus组)、阳性药物组(泰必利组),每组12只.Control组腹腔注射生理盐水,其余各组大鼠腹腔注射3,3-亚氨基二丙腈(IDPN)建立TS大鼠模型.采用双盲法检测大鼠行为学,ELISA法检测5-羟色胺(5-HT)、多巴胺(DA)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平,Western blot法和免疫组织化学染色法检测相关蛋白表达.结果 与Control组比较,TS组大鼠运动行为学评分和刻板行为学评分升高,血清和纹状体中IL-6、IL-1β、TNF-α水平均升高,纹状体中5-HT、DA水平均降低,脑源性神经营养因子(BDNF)蛋白表达量降低,磷酸化核转录因子-κB p65(p-NF-κB p65)和磷酸化NF-κB抑制蛋白α(p-IKBα)蛋白表达量均增加(均P<0.05);与TS组比较,L-Mus组、H-Mus组和泰必利组大鼠上述指标均显著改善,且H-Mus组和泰必利组大鼠各指标改善程度均显著优于L-Mus组(均P<0.05).结论 麝香酮能够改善TS大鼠行为学和神经炎症,其作用机制可能与调控BDNF/NF-κB信号通路有关.
Objective To study the effects of muscone on the behavior and neuroinflammation of Tourette syndrome(TS)rats,and its related mechanisms.Methods Sixty rats were randomly divided into control group(Control group),model group(TS group),low-dose muscone group(L-Mus group),high-dose muscone group(H-Mus group)and positive drug group(Tia-pride group),with 12 rats in each group.Rats in Control group were intraperitoneally injected with normal saline,and rats in other groups were intraperitoneally injected with 3,3-iminodipropanitrile(IDPN)to establish TS rat model.The behavior of rats was measured by double-blind method.The levels of 5-hydroxytryptamine(5-HT),dopamine(DA),interleukin-6(IL-6),inter-leukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)were measured by ELISA,the protein expression was detected by Western blot and immunohistochemistry.Results Compared with Control group,the scores of exercise behavior and stereotyped behav-ior of rats in TS group were increased.The levels of IL-6,IL-1β and TNF-α in serum and striatum were increased,and the levels of 5-HT and DA in striatum were decreased.The protein expression of brain-derived neurotrophic factor(BDNF)was de-creased.The protein expressions of phosphorylated nuclear factor kappa B p65(p-NF-κB p65)and phosphorylated NF-κB inhibi-tory protein α(p-IKBα)were increased(all P<0.05).Compared with TS group,the levels of the above indicators of rats in L-Mus group,H-Mus group and Tiapride group were significantly improved,and the improvement degree of all indicators level of rats in H-Mus group and Tiapride group were significantly better than that in L-Mus group(all P<0.05).Conclusion Mus-cone can improve the behavior and neuroinflammation condition of TS rats,and its mechanism may be related to the regulation of BDNF/NF-κB signaling pathway.

musconeTourette syndromeneuroinflammationstriatumBDNF/NF-κB signaling pathway

吴春霞、刘洋、牡兰、宝高娃、苏布德格日乐、斯琴格日勒

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内蒙古民族大学附属医院蒙西医结合儿科,通辽 028007

内蒙古民族大学附属医院蒙西医结合神经内科,通辽 028007

麝香酮 多发性抽动症 神经炎症 纹状体 BDNF/NF-κB信号通路

2024

华中科技大学学报(医学版)
华中科技大学

华中科技大学学报(医学版)

CSTPCD北大核心
影响因子:1.443
ISSN:1672-0741
年,卷(期):2024.53(6)