NWIPB OpenIR
低氧下下丘脑神经肽的分泌及调节
吴雁
学位类型博士
导师杜继曾
1998
学位授予单位中国科学院西北高原生物研究所
学位授予地点中国科学院西北高原生物研究所
学位专业动物学
关键词高原鼠兔 Aⅱ Β-ep 新生大鼠 低氧
摘要本论文利用人工模拟高原低气压低氧的方法,研究了不同海拔,不同时间低氧条件下大鼠及高原鼠兔的下丘脑-垂体-肾上腺皮质轴的活动及变化规律。观察了低氧条件下下丘脑促ACTH分泌因子CRF和AVP在ME处的分泌变化,外周血浆中肾上泉皮质激素水平的变化,以及低氧条件下AⅡ及β-EP对HPA轴活动的调节以及新生大鼠对急性低氧的应答反应及AⅡ和β-EP对新生大鼠CRF分泌活动的调节。结果如下: 一. 急性低氧(0.5、1h、2h、24h)暴露可激活大鼠下丘脑-垂体-肾上腺皮质轴活动,使血浆皮质酮水平升高;ME处CRF含量下降,分泌入脉血中的CRF增加。5km 低氧组血浆皮酮分别升高275.89%(p < 0.01),211.83%(p < 0.01),127.08%(p < 0.05)和17.42;7km低氧组血浆质酮分别升高452.96%(p < 0.001),484.75%(p < 0.001),216.90%(p < 0.01)和85.41%(p < 0.01)。低氧2h,24h后,5km组ME处CRF含量分别下降33.54%(p < 0.05)。5d亚急性低氧暴露后,ME处CRF的分泌活动及肾上腺皮质的分泌活动都已开始调整;5km组血浆皮质酮水平升高16.49%,ME处CRF含量长高5.93%;7km组血浆皮质酮下降19.76%,ME处CRF含量下降22.73%。慢性低氧暴露15d后,ME处CRF的分泌活动和肾上腺皮质的分泌活动基本接近对照组,5km组血浆皮质酮升高13.84%,ME处CRF含量升高19.40%。二. 低氧条件下ME处AVP的分泌活动无显著变化。低氧2h和24h后5km和7km组分别升高10.18%,20.91%和33.80%和25.00%。低氧暴露5d后分别升高11.52%和13.43%。低氧15d后低氧组ME处AVP含量降低32.16%。但ME处AVP/CRF的比率在整个低氧过程中却是变化的。急性低氧2h、24h时,AVP/CRF的比率高于对照组。5km组分别高于对照组23.04%和28.81%;7km组升高50.22%和32.69%。5d亚急性低氧期AVP/CRF的比率接近对照5km组和7km组分别比对早下降和升高6.75%,46.81%。而15d慢性低氧后,AVP/CRF比率低于对照组90.34%(p < 0.01)。三. 脑室给β-EP后再急性7km低氧暴露2h,β-EP对低氧引起的CRF分泌有明显抑制作用(p < 0.05),对肾上腺皮质的分泌活动也有显著抑制作用(p < 0.05)。β-EP的这种抑制作用可纳洛酮部分反转。四. 脑室注射AⅡ对急性低氧暴露引起的HPA轴的活动有效增强作用,它可使血浆皮质酮水平显著升高(p < 0.05),AⅡ的这种作用可能是通过使ME处的AVP分泌增加(p < 0.01)而实现的。脑室同时给予AⅡ和AⅡ抗体后,AⅡ对HPA轴的增强作用消失。五. 急性低氧暴露2h时,可激活新生20d龄大鼠的HPA轴活动,ME处CRF含量下降(p < 0.05)。六. 新生20d大鼠脑室给AⅡ,AⅡ+Ab及β-EP,β-EP+Nal后,再急性低氧暴露2h,AⅡ及β-EP对ME处CRF、AVP分泌活动都无显著影响,AⅡ对血浆皮质酮水平也无明显作用,β-EP使血浆皮质酮水平下降。但无统计学意义。七. 无论急性低氧还是亚急性低氧都不能激活高原鼠兔的HPA轴活动,脑室给予AⅡ及β-P再急性低氧暴露,AⅡ及β-EP对高原鼠兔的HPA活动无显著影响。结果表明: 1. 低氧可激活大鼠的HPA轴活动。使ME处CRF含量下降,血浆皮质酮水平升高。2. AⅡ对低氧引起的HPA轴的活动有增强作用。AⅡ可能通过增加ME处AVP的分泌,增强肾上腺皮质酮分泌。3. β-EP对低氧引起的HPA轴活动有抑制作用,抑制低氧引起的CRF分泌和皮质酮分泌。4. 低氧对新生大鼠HPA轴活动同样具有刺激作用,低氧可促使CRF和皮质酮分泌增加。5. AⅡ和β-EP对新生大鼠CRF、AVP的分泌活动都无显著作用。AⅡ同样不影响皮质酮的分泌。β-EP可使血浆皮质酮水平下降。6. 低氧暴露后高原鼠兔HPA轴的活动不变。AⅡ、β-EP不能明显影响高原鼠兔的HPA轴活动。高原鼠兔表现出很强的低氧耐受性和对AⅡ、β-EP的不敏感性。由上述结果推断: 低氧条件下对大鼠HPA轴调节至少是通过改变ME处CRF和AVP的分泌活动实现的;20d龄新年大鼠已具低氧应激能力;高原鼠兔在神经内分泌活动中表现出其低氧适应性。
其他摘要The activity of Hypothalamo-pituitary-adrenalcortex(HPA) axis of rat and Ochotona curzoniea was studied under the different conditions of hypoxia. We observed the changes of secretion of corticotropin-releasing factor(CRF) and arginin vasopressin(AVP) in median eminence(ME), of level of plasma corticosterone. We also observed the effects of angiotensin II (AII)and β-endorphin on activity of HPA by using the method of icv. Then the activity of HPA of neonatal rat under hypoxia and the modulation of AII and β-endorphin to HPA were investigated. The results are as follows: 1. Hypoxia activated the HPA axis of rat. During period of acute hypoxia, the activity of HPA increased. The level of plasma corticosterone rose and the secretion of CRF increased at both altitudes of 5km and 7km. After 5d exposing to hypoxia, the regulation of HPA activity has begun. When rat was exposed to hypoxia for 15d, it has adapted itself to hypoxia. 2. During hypoxia the secretion of AVP in ME is unchanged, but the ratio of AVP/CRF rose above that of control during acute period of hypoxia, then decreased with time exposed to hypoxia. After 15d of hypoxia the ratio is below that of the control significantly. 3. icv. AII can make ME increase secretion of AVP to portal blood and level of plasma corticosterone increased. But content of CRF in ME unchanged. 4. β-endorphin administration by icv. inhibit release of CRF from ME and corticosterone from adrenolcortex. 5. The HPT of neonatal rat responsed to acute hypoxia. The release of CRF to portal blood increased and the level of plasma corticosterone rose. 6. Administration AII and β-endorphin by icv. Had no significant effects on contents of CRF and AVP in ME. AII also did not affects the level of plasma corticosterone but β-endorphin is likely to have a inhibit effect on level of plasma corticosterone, but the mechanism is unknown. 7. Hypoxia can't activate the activity of HPA of Ochotona curzoniae. Had not only AII but also β-endorpnin effects on CRF and AVP release in ME. These results suggest that a). Hypoxia can activate the activity of HPA in rat as a stressor. b). Under the condition of hypoxia, AII may augment the activity of HPA induced by hypoxia by the way of increasing secretion of AVP. c). β-endorphin may inhibit the activity of HPA under the condition of hypoxia by decreasing the secretion of CRF from ME. d). AII and β-endorphin are likely to have no influence on HPA in neonatal rat. f). In Ochotona curzoniae the activity of HPA doesn't activate by hypoxia. g). The activity of HPA is not sensitive to AII and β-endorphin. So we deduced from the results that hyproxia modulate the activity of HPA by changing the secretion of CRF and AVP in ME. Neonatal rat has the ability to response to hypoxia. Ochotona curzoniae is adaptated to hypoxia in neuroendocrinology.
页数68
语种中文
文献类型学位论文
条目标识符http://210.75.249.4/handle/363003/3382
专题中国科学院西北高原生物研究所
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吴雁. 低氧下下丘脑神经肽的分泌及调节[D]. 中国科学院西北高原生物研究所. 中国科学院西北高原生物研究所,1998.
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