摘要
目的:探讨孤啡肽(nociceptin/orphanin FQ,N/OFQ)对尼古丁(nicotine,NIC)戒断大鼠焦虑样行为的改善作用及其对下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenal,HPA)轴神经递质与炎症因子表达的调控机制。方法:成年雄性Sprague-Dawley大鼠32只,随机分为正常对照组、NIC戒断模型组、N/OFQ低剂量治疗组和N/OFQ高剂量治疗组,每组各8只。模型组和N/OFQ治疗组大鼠每次皮下注射NIC(0.4 mg/kg),每天2次,连续7 d,然后戒断3 d制备大鼠尼古丁戒断焦虑模型。戒断期间N/OFQ低、高剂量治疗组大鼠每天一次侧脑室注射N/OFQ 1nmol和N/OFQ 10 nmol,连续3 d。第3次给药10 min后,利用旷场实验(open filed,OF)和高架十字迷宫实验(elevated plus maze,EPM)检测大鼠行为学变化;ELISA检测血清中促肾上腺皮质激素释放激素(corticotrophin-releasing hormone,CRH)、促肾上腺皮质激素(adrenocor ticotropic hormore,ACTH)和皮质酮(coritosterone,CORT)浓度以及血清中炎症因子肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素1β(interleukin-1β,IL-1β)和IL-6的浓度;用RT-qPCR检测大脑杏仁核中央核(centraln nucleus of amygdala,CeA)中TNF-α、IL-1β和IL-6的mRNA表达水平;HE染色光镜下观察海马组织CA1区神经元形态学变化;利用高效液相色谱检测大脑CeA的去甲肾上腺素(norepinephrine,NE)水平;利用Western blot检测大脑CeA的酪氨酸羟化酶(tyrosine hydroxylase,TH)蛋白表达。结果:与模型组比较,N/OFQ低、高剂量治疗组大鼠在OF中央区活动距离和活动时间显著升高(P<0.05或P<0.01),EPM的开放臂进入次数和停留时间百分率显著升高(P<0.05或P<0.01);同时,N/OFQ低、高剂量治疗组显著抑制NIC戒断大鼠血清中CRH、ACTH和CORT浓度(P<0.01);显著抑制血清中TNF-α、IL-1β和IL-6等炎症因子水平以及大脑CeA中TNF-α、IL-1β和IL-6 mRNA表达水平(P<0.05或P<0.01);N/OFQ低、高剂量治疗组显著减轻大鼠海马CA1区神经元损伤;并且显著降�
AIM:To investigate the ameliorative effect of nociceptin/orphanin(N/OFQ)on anxiety-like behavior in nicotine(NIC)withdrawal-induced rats and its regulatory mechanisms on the expression of neurotransmitters associated with the hypothalamic-pituitary-adrenal(HPA)axis and inflammatory factors.METHODS:Thirty-two adult male Sprague-Dawley rats were randomly divided into 4 groups:normal control group,NIC withdrawal model group,low-dose N/OFQ treatment group,and high-dose N/OFQ treatment group,with 8 rats in each group.To establish NIC withdrawal model,the rats in the NIC model and N/OFQ treatment groups were subcutaneously injected with NIC(0.4 mg/kg),twice a day for 7 consecutive days followed by 3 days of withdrawal.During the withdrawal period,the rats in the low and high-dose N/OFQ treatment groups received intracerebroventricular injection of N/OFQ(1 nmol or 10 nmol)once per day for 3 consecutive days.Ten minutes after the third administration,all rats underwent open filed(OF)and elevated plus maze(EPM)tests to detect behavioral changes.The serum concentrations of corticotrophin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),corticosterone(CORT),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 were measured by ELISA.The mRNA expression levels of TNF-α,IL-1βand IL-6 in the central nucleus of the amygdala(CeA)of the brain were detected by RT-qPCR.Histological changes in neuron morphology in the CA1 region of the hippocampus were observed under a light microscope following hematoxylin and eosin(HE)staining.Norepinephrine(NE)levels in the CeA of the brain were determined by HPLC.The protein expression of tyrosine hydroxylase(TH)in the CeA of the brain was detected by Western blot.RESULTS:Compared with the NIC withdrawal model group,rats in the low and high-dose N/OFQ treatment groups showed significant increase in the distance and time spent in the central area of the open field(P<0.05 or P<0.01),as well as significant increase in the number of entries and the percentage of time spent in th
作者
吴朋烊
赵容杰
李露露
李秋月
张春晶
吴丽娜
赵正林
WU Pengyang;ZHAO Rongjie;LI Lulu;LI Qiuyue;ZHANG Chunjing;WU Lina;ZHAO Zhenglin(College of Medical Technology,Qiqihar Medical University,Qiqihar 161006,China;College of Mental Health,Qiqihar Medical University,Qiqihar 161006,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2024年第10期1926-1933,共8页
Chinese Journal of Pathophysiology
基金
齐齐哈尔市科技计划联合引导项目(No.LHYD-202011)
黑龙江省省属高等学校基本科研业务费科研项目(No.2022-KYYWF-0830)
齐齐哈尔医学科学院重点培育项目(No.2021-ZDPY-014)。
关键词
孤啡肽
尼古丁戒断焦虑
下丘脑-垂体-肾上腺轴
炎症因子
去甲肾上腺素
酪氨酸羟化酶
nociceptin/orphanin
nicotine withdrawal anxiety
hypothalamic-pituitary-adrenal axis
inflammatory factors
norepinephrine
tyrosine hydroxylase
