中枢胆碱能系统对颈动脉窦压力感受性反射的影响及其机制

发布时间：2018-05-10 12:27

本文选题：颈动脉窦压力感受性反射 + 毒扁豆碱　；参考：《苏州大学》2009年硕士论文

【摘要】： 目的:探讨中枢胆碱能系统在常态下对大鼠颈动脉窦压力感受性反射(Carotid sinus baroreceptor reflex, CSR)的影响及其可能的调节机制。方法: 孤离麻醉SD大鼠的双侧颈动脉窦区,向一侧孤离窦及股动脉内各插一导管,分别经压力换能器同步记录窦内压(intracarotid sinus pressure, ISP)和平均动脉血压(mean arterial pressure, MAP);ISP以40 mmHg为一阶梯由0逐级加压至280 mmHg(每级停留4 sec),然后以同样的梯级减压至0;将各级ISP与其对应的MAP数值进行Logistic五参数曲线拟合,获取ISP-MAP、ISP-Gain(增益)关系曲线及其反射特征参数;在不影响基础血压水平的前提下,通过侧脑室及核团(蓝斑、孤束核)微量注射胆碱酯酶抑制剂毒扁豆碱(physostigmine, PHY)以及各种选择性胆碱能受体拮抗剂,观察中枢胆碱能系统对CSR的调制作用及其机制。结果: 1.侧脑室注射毒扁豆碱(PHY)对CSR的影响分别侧脑室注射(intracerebroventricular injection, i. c. v.)小、中、大3种微剂量的PHY后,均导致ISP-MAP关系曲线剂量依赖性的显著上移(P 0.05),ISP-Gain关系曲线中部剂量依赖性的明显下移(P 0.05),反射参数中调定点、饱和压和最大增益时的窦内压值增大(P 0.05),MAP反射变动范围及反射最大增益减小(P 0.05),表明脑内胆碱可明显引起CSR抑制性重调定。 2.预先i. c. v.选择性胆碱能受体拮抗剂对侧脑室给PHY所致CSR抑制的影响 2.1单独i. c. v.所给剂量的M_1受体拮抗剂哌仑西平(prienzepine, PRZ)或M_2受体拮抗剂美索曲明(methoctramine, MTR)或N_1受体拮抗剂六烃季胺(hexamethonium, HEX),均对CSR无明显影响(P 0.05); 2.2但预先i. c. v.相应剂量的PRZ或MTR后,均能不同程度的缓解i. c. v. PHY对CSR的抑制性重调定(P 0.05),表现为:ISP-MAP关系曲线显著下移,ISP-Gain关系曲线明显上移,饱和压和最大增益时的窦内压值下降,MAP反射变动范围及反射最大增益加大;且阻断M_2受体比阻断M_1受体的缓解效应更加明显(P 0.05);而预先i. c. v.相应剂量的HEX,对i. c. v. PHY引起的CSR的重调定没有明显作用(P 0.05)。 3.预先蓝斑内注射选择性胆碱能受体拮抗剂对i.c.v. PHY所致CSR抑制的影响 3.1单独向蓝斑(locus ceruleus, LC)内注射所给剂量的PRZ或MTR或HEX,也对CSR均无明显影响(P 0.05); 3.2预先向LC内微量注射相应剂量的M_1或M_2受体拮抗剂PRZ或MTR,对i. c. v. PHY所致CSR抑制性重调定的影响结果,类似于结果2.2,且PRZ的这种减弱作用不如MTR的显著(P 0.05);预先向LC内注射相应剂量的N_1受体拮抗剂HEX,也对i. c. v. PHY引起的CSR的重调定没有明显影响(P 0.05)。 4、预先孤束核内注射选择性胆碱能受体拮抗剂对i.c.v. PHY所致CSR抑制的影响 4.1单独向孤束核(nucleus tractus solitarius, NTS)内注射所给剂量的PRZ或MTR或HEX,对CSR仍无明显影响(P 0.05); 4.2预先向NTS内微量注射相应剂量的M_1或M_2受体拮抗剂PRZ或MTR,均可明显增强i. c. v. PHY对CSR的抑制效应(P 0.05);且NTS内预先注射MTR,与NTS内预先注射PRZ相比,更加明显增强i. c. v. PHY对CSR的上述抑制效应(P 0.05)。预先向NTS内注射相应剂量的HEX,仍对i. c. v. PHY引起的CSR抑制效应没有明显作用(P 0.05)。结论: 1.侧脑室给予拟胆碱药(毒扁豆碱)对颈动脉窦压力感受性反射(CSR)具有明显的剂量依赖性抑制作用。 2.预先i. c. v. M_1或M_2受体拮抗剂可减弱i. c. v. PHY对CSR的抑制性重调定,M_2受体拮抗剂的缓解作用大于M_1受体拮抗剂;N_1受体拮抗剂则无明显作用。提示下丘脑室周核团的M_1、M_2受体参与介导脑内胆碱能系统对CSR的抑制性重调定,且M_2受体作用大于M_1受体。 3.预先向蓝斑(LC)内微量注射M_1受体或M_2受体拮抗剂后,再i. c. v. PHY,对CSR的影响则与结论2类似,且LC处M_2受体拮抗剂的缓解作用大于M_1受体拮抗剂;N_1受体拮抗剂则无明显作用。提示LC的M_1、M_2受体参与介导中枢胆碱能系统对CSR的抑制性重调定,且LC的M_2受体作用大于M_1受体,下丘脑-LC的胆碱能通路可能是脑胆碱系统调节CSR机能的下行通路之一。 4.预先向孤束核(NTS)内微量注射M_1受体或M_2受体拮抗剂后,再i. c. v. PHY,对CSR的影响则与结论2、3相反,可强化i. c. v. PHY对CSR的抑制性重调定;M_2受体拮抗剂的强化作用明显高于M_1受体拮抗剂;N_1受体拮抗剂则无明显影响。提示NTS的M_1、M_2受体尤为M_2受体可弱化i. c. v. PHY对CSR的抑制性重调定,下丘脑-NTS胆碱能通路可能也是脑胆碱系统整合CSR机能的下行通路之一。 5.下丘脑、蓝斑和孤束核的N_1受体可能与中枢胆碱能系统对CSR的抑制性重调定无关。
[Abstract]:Objective: To investigate the effect of the central cholinergic system on the Carotid sinus baroreceptor reflex (CSR) and the possible regulatory mechanism of the carotid sinus baroreceptor reflex (CSR) in rats.
Method:
In the bilateral carotid sinus area of the isolated SD rats, a catheter was inserted into the isolated paranus and femoral artery on one side, and the internal pressure (intracarotid sinus pressure, ISP) and the mean arterial blood pressure (mean arterial pressure, MAP) were recorded by the pressure transducer respectively. The ISP was 40 mmHg as a step from 0 to 280 mmHg (4). After decompressing the same ladder to 0, the ISP and its corresponding MAP values were fitted with the Logistic five parameter curve to obtain the ISP-MAP, ISP-Gain (gain) relation curve and its reflecting characteristic parameters. The cholinesterase inhibitor poison lentil was microinjected through the lateral ventricle and nucleus (locus coeruleus, soliton nucleus) without affecting the basic blood pressure level. Physostigmine (PHY) and various selective cholinergic receptor antagonists were used to observe the modulation effect of central cholinergic system on CSR and its mechanism.
Result:
The effect of 1. lateral ventricle injection of PHY on CSR
Intracerebroventricular injection, I. C. v. (I. C. v.) were small, medium and large doses of PHY, all of which resulted in a significant increase in the dose dependence of the ISP-MAP relationship curve (P 0.05), the obvious downshift of the dose dependence of the ISP-Gain relationship curve (P 0.05), the modulation point of the reflection parameters, the saturation pressure and the internal pressure value at the maximum gain. Increased (P 0.05), decreased the range of MAP reflex and the maximum reflection gain (P 0.05), indicating that intracerebral cholinergic could significantly induce CSR inhibitory reconditioning.
2. effect of selective I. C. v. selective cholinergic receptor antagonist on CSR inhibition induced by PHY in lateral ventricle
2.1 the dose of M_1 receptor antagonist piperon Xiping (prienzepine, PRZ) or M_2 receptor antagonist, melostramine (methoctramine, MTR) or N_1 receptor antagonist six hydrocarbon quaternary amine (hexamethonium, HEX), gave no significant influence on the dosage of 2.1 individual I. C. v.;
2.2 but after the corresponding dose of PRZ or MTR of pre I. C. v., the inhibitory remodulation (P 0.05) of I. C. v. PHY (P) can be alleviated in varying degrees. The remission effect of blocking the M_2 receptor was more obvious than that of blocking the M_1 receptor (P 0.05), while the HEX in the corresponding dose of pre I. C. v. did not significantly affect the CSR remodulation induced by I. C. v. PHY (0.05).
3. the effect of selective blue cholinergic receptor antagonist on CSR inhibition induced by i.c.v. PHY
3.1 injection of PRZ or MTR or HEX to locus ceruleus (LC) alone had no significant effect on CSR (P 0.05).
3.2 the corresponding dose of M_1 or M_2 receptor antagonist PRZ or MTR was injected into LC in advance, and the result of I. C. v. PHY induced CSR inhibitory remodulation was similar to that of result 2.2, and PRZ was less significant than MTR (0.05); The remodulation was not significantly affected (P 0.05).
4, the effect of selective cholinergic receptor antagonist injected into the nucleus of the solitary tract on the inhibition of CSR induced by i.c.v. PHY.
4.1 injection of PRZ or MTR or HEX to the nucleus tractus solitarius (NTS) alone had no significant effect on CSR (P 0.05).
4.2 a pre injected dose of M_1 or M_2 receptor antagonist PRZ or MTR in NTS can obviously enhance the inhibitory effect of I. C. v. PHY on CSR (P 0.05). X still had no significant effect on CSR inhibition effect induced by I. C. v. PHY (P 0.05).
Conclusion:
The 1. ventricle given the cholinergic drug (physostigmine) had a dose-dependent inhibitory effect on carotid sinus baroreceptor reflex (CSR).
2. pre I. C. v. M_1 or M_2 receptor antagonists can weaken the inhibitory remodulation of I. C. v. PHY to CSR, and the alleviating effect of M_2 receptor antagonist is greater than that of M_1 receptor antagonist; The body effect is greater than the M_1 receptor.
3. after microinjection of M_1 receptor or M_2 receptor antagonist in LC to I. C. v. PHY, the effect on CSR was similar to that of conclusion 2, and the relieving effect of M_2 receptor antagonist at LC was greater than that of M_1 receptor antagonist, and N_1 receptor antagonist had no obvious effect. The M_2 receptor of LC is stronger than that of M_1 receptor. The cholinergic pathway of -LC in hypothalamus may be one of the descending pathways of the cholinergic system regulating CSR function.
4. after the microinjection of M_1 receptor or M_2 receptor antagonist to the nucleus of the solitary tract (NTS), then I. C. v. PHY, the effect on CSR was contrary to the conclusion of 2,3, which enhanced the inhibitory remodulation of I. C. v., and the strengthening effect of the receptor antagonist was obviously higher than that of the receptor antagonist; In particular, the M_2 receptor may weaken the inhibitory remodulation of I. C. v. PHY to CSR, and the -NTS cholinergic pathway in the hypothalamus may also be one of the downlink pathways of the cerebral choline system to integrate CSR function.
5. the N_1 receptor in the hypothalamus, locus coeruleus and nucleus tractus soliton may be independent of central cholinergic system on the inhibitory reconditioning of CSR.

【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R33

【参考文献】