摘要
目的 用 6 OHDA分别选择性地损毁外周和中枢的去甲肾上腺素 (NE)能系统 ,探讨去甲肾上腺素能系统在冷应激诱导大鼠NK细胞活性下降中的作用。方法 大鼠置于4℃的冷室 4h。腹腔和侧脑室分别注射 6 OHDA。采用YAC 1细胞51Cr释放法测定脾脏NK细胞的活性。用免疫细胞化学法观察下丘脑室旁核 (PVN)和脑干蓝斑 (LC)中的Fos表达 ,以及Fos表达阳性的神经元的性质。用放射免疫法测定血浆CORT的浓度。结果 脑室注射 6 OHDA能部分翻转冷应激诱导的血浆CORT浓度的升高 ,减少PVN和LC中Fos的表达 ,同时使脾脏NK细胞活性不再下降。同样 ,腹腔注射 6 OHDA也能翻转冷应激诱导NK细胞活性的下降 ,但对脑内Fos表达没有明显影响。另外 ,双染实验表明 ,PVN中有少量的Fos阳性的神经元同时表达精氨酸加压素 (AVP)或催产素 (OT) ,而LC中大多数Fos阳性的神经元同时表达酪氨酸羟化酶 (TH)。结论 冷应激诱导大鼠NK细胞活性下降的可能机制是 :一方面通过中枢去甲肾上腺素能系统去激活HPA轴 ;另一方面介导外周交感神经系统。最后两者共同作用于脾脏NK细胞 ,导致其活性下降。
Aim To investigate the role of locus coeruleus(LC)-norepinephrinergic system and sympathetic nervous system in immunosuppression under cold stress, using 6-hydroxydopamine(6-OHDA) as chemical sympathectomy.Methods Rats were maintained in cold chamber at 4℃ for 4 h.The 51Cr release assay from YAC-1 cells was used to determine the splenic NK cell activity, the double staining of ABC method was employed to observe the immunoreactive expression of Fos, arginine-vasopressin(AVP), oxytocin(OT) and tyrosine hydroxylase(TH), and conventional radioimmunoassay was used to measure plasma corticosterone (CORT) concentrations.Results Central sympathectomy with intracerebroventricular(i.c.v.) injection of 6-OHDA r educed significantly the elevation of plasma corticosterone level, the expressio n of Fos in hypothalamic paraventricular nucleus(PVN) and in locus coeruleus(LC ), as well as the suppression of NK activity induced by cold stress at 4℃ for 4 h. Peripheral sympathectomy with intraperitoneal (i.p.) injection of 6-OHDA al so reversed the cold stress-induced suppression of NK cytotoxicity, but without significant effect on Fos expression in brain. Double staining showed that amon g the Fos-positive neurons in PVN only a few co-expressed Fos and AVP or Fos a nd OT, while in LC the majority of Fos-positive neurons co-expressed Fos and T H.Conclusion The mechanism of suppression of NK activity induce d by cold stress may be mediated through HPA axis activated partially by central LC-norepinephrinergic system and through the peripheral sympathetic nervous system.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2004年第10期1167-1170,共4页
Chinese Pharmacological Bulletin
基金
中日校际合作研究基金资助项目 (EE13 40 0 5 )
关键词
冷应激
NK细胞活性
去甲肾上腺素能系统
FOS
皮质酮
下丘脑室旁核
蓝斑
免疫抑制
cold stress
natural killer cytotoxicity
norepinephri nergic nervous system
Fos
corticosterone
paraventricular nucleus
locus coeru leus
immunosuppression
