本文選題：頸動脈竇壓力感受性反射 + 毒扁豆堿�。� 參考：《蘇州大學(xué)》2009年碩士論文

【摘要】： 目的:探討中樞膽堿能系統(tǒng)在常態(tài)下對大鼠頸動脈竇壓力感受性反射(Carotid sinus baroreceptor reflex, CSR)的影響及其可能的調(diào)節(jié)機制。 方法: 孤離麻醉SD大鼠的雙側(cè)頸動脈竇區(qū),向一側(cè)孤離竇及股動脈內(nèi)各插一導(dǎo)管,分別經(jīng)壓力換能器同步記錄竇內(nèi)壓(intracarotid sinus pressure, ISP)和平均動脈血壓(mean arterial pressure, MAP);ISP以40 mmHg為一階梯由0逐級加壓至280 mmHg(每級停留4 sec),然后以同樣的梯級減壓至0;將各級ISP與其對應(yīng)的MAP數(shù)值進(jìn)行Logistic五參數(shù)曲線擬合,獲取ISP-MAP、ISP-Gain(增益)關(guān)系曲線及其反射特征參數(shù);在不影響基礎(chǔ)血壓水平的前提下,通過側(cè)腦室及核團(tuán)(藍(lán)斑、孤束核)微量注射膽堿酯酶抑制劑毒扁豆堿(physostigmine, PHY)以及各種選擇性膽堿能受體拮抗劑,觀察中樞膽堿能系統(tǒng)對CSR的調(diào)制作用及其機制。 結(jié)果: 1.側(cè)腦室注射毒扁豆堿(PHY)對CSR的影響 分別側(cè)腦室注射(intracerebroventricular injection, i. c. v.)小、中、大3種微劑量的PHY后,均導(dǎo)致ISP-MAP關(guān)系曲線劑量依賴性的顯著上移(P 0.05),ISP-Gain關(guān)系曲線中部劑量依賴性的明顯下移(P 0.05),反射參數(shù)中調(diào)定點、飽和壓和最大增益時的竇內(nèi)壓值增大(P 0.05),MAP反射變動范圍及反射最大增益減小(P 0.05),表明腦內(nèi)膽堿可明顯引起CSR抑制性重調(diào)定。 2.預(yù)先i. c. v.選擇性膽堿能受體拮抗劑對側(cè)腦室給PHY所致CSR抑制的影響 2.1單獨i. c. v.所給劑量的M_1受體拮抗劑哌侖西平(prienzepine, PRZ)或M_2受體拮抗劑美索曲明(methoctramine, MTR)或N_1受體拮抗劑六烴季胺(hexamethonium, HEX),均對CSR無明顯影響(P 0.05); 2.2但預(yù)先i. c. v.相應(yīng)劑量的PRZ或MTR后,均能不同程度的緩解i. c. v. PHY對CSR的抑制性重調(diào)定(P 0.05),表現(xiàn)為:ISP-MAP關(guān)系曲線顯著下移,ISP-Gain關(guān)系曲線明顯上移,飽和壓和最大增益時的竇內(nèi)壓值下降,MAP反射變動范圍及反射最大增益加大;且阻斷M_2受體比阻斷M_1受體的緩解效應(yīng)更加明顯(P 0.05);而預(yù)先i. c. v.相應(yīng)劑量的HEX,對i. c. v. PHY引起的CSR的重調(diào)定沒有明顯作用(P 0.05)。 3.預(yù)先藍(lán)斑內(nèi)注射選擇性膽堿能受體拮抗劑對i.c.v. PHY所致CSR抑制的影響 3.1單獨向藍(lán)斑(locus ceruleus, LC)內(nèi)注射所給劑量的PRZ或MTR或HEX,也對CSR均無明顯影響(P 0.05); 3.2預(yù)先向LC內(nèi)微量注射相應(yīng)劑量的M_1或M_2受體拮抗劑PRZ或MTR,對i. c. v. PHY所致CSR抑制性重調(diào)定的影響結(jié)果,類似于結(jié)果2.2,且PRZ的這種減弱作用不如MTR的顯著(P 0.05);預(yù)先向LC內(nèi)注射相應(yīng)劑量的N_1受體拮抗劑HEX,也對i. c. v. PHY引起的CSR的重調(diào)定沒有明顯影響(P 0.05)。 4、預(yù)先孤束核內(nèi)注射選擇性膽堿能受體拮抗劑對i.c.v. PHY所致CSR抑制的影響 4.1單獨向孤束核(nucleus tractus solitarius, NTS)內(nèi)注射所給劑量的PRZ或MTR或HEX,對CSR仍無明顯影響(P 0.05); 4.2預(yù)先向NTS內(nèi)微量注射相應(yīng)劑量的M_1或M_2受體拮抗劑PRZ或MTR,均可明顯增強i. c. v. PHY對CSR的抑制效應(yīng)(P 0.05);且NTS內(nèi)預(yù)先注射MTR,與NTS內(nèi)預(yù)先注射PRZ相比,更加明顯增強i. c. v. PHY對CSR的上述抑制效應(yīng)(P 0.05)。預(yù)先向NTS內(nèi)注射相應(yīng)劑量的HEX,仍對i. c. v. PHY引起的CSR抑制效應(yīng)沒有明顯作用(P 0.05)。 結(jié)論: 1.側(cè)腦室給予擬膽堿藥(毒扁豆堿)對頸動脈竇壓力感受性反射(CSR)具有明顯的劑量依賴性抑制作用。 2.預(yù)先i. c. v. M_1或M_2受體拮抗劑可減弱i. c. v. PHY對CSR的抑制性重調(diào)定,M_2受體拮抗劑的緩解作用大于M_1受體拮抗劑;N_1受體拮抗劑則無明顯作用。提示下丘腦室周核團(tuán)的M_1、M_2受體參與介導(dǎo)腦內(nèi)膽堿能系統(tǒng)對CSR的抑制性重調(diào)定,且M_2受體作用大于M_1受體。 3.預(yù)先向藍(lán)斑(LC)內(nèi)微量注射M_1受體或M_2受體拮抗劑后,再i. c. v. PHY,對CSR的影響則與結(jié)論2類似,且LC處M_2受體拮抗劑的緩解作用大于M_1受體拮抗劑;N_1受體拮抗劑則無明顯作用。提示LC的M_1、M_2受體參與介導(dǎo)中樞膽堿能系統(tǒng)對CSR的抑制性重調(diào)定,且LC的M_2受體作用大于M_1受體,下丘腦-LC的膽堿能通路可能是腦膽堿系統(tǒng)調(diào)節(jié)CSR機能的下行通路之一。 4.預(yù)先向孤束核(NTS)內(nèi)微量注射M_1受體或M_2受體拮抗劑后,再i. c. v. PHY,對CSR的影響則與結(jié)論2、3相反,可強化i. c. v. PHY對CSR的抑制性重調(diào)定;M_2受體拮抗劑的強化作用明顯高于M_1受體拮抗劑;N_1受體拮抗劑則無明顯影響。提示NTS的M_1、M_2受體尤為M_2受體可弱化i. c. v. PHY對CSR的抑制性重調(diào)定,下丘腦-NTS膽堿能通路可能也是腦膽堿系統(tǒng)整合CSR機能的下行通路之一。 5.下丘腦、藍(lán)斑和孤束核的N_1受體可能與中樞膽堿能系統(tǒng)對CSR的抑制性重調(diào)定無關(guān)。
[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.

【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2009
【分類號】：R33

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 潘玉貞,吳建群,王紹;乙酰膽堿(Ach)興奮外側(cè)韁核拮抗電針鎮(zhèn)痛[J];長春中醫(yī)學(xué)院學(xué)報;1997年01期

2 姚敏,金玉祥,姜虹;慢性應(yīng)激對大鼠腦內(nèi)乙酰膽堿酯酶活性的影響[J];華北國防醫(yī)藥;2003年02期

3 王志紅;藍(lán)斑核內(nèi)注入乙酰膽堿、新斯的明及膽堿能受體阻斷劑對迷走—加壓反應(yīng)的影響[J];曲阜師范大學(xué)學(xué)報(自然科學(xué)版);1998年02期

4 賈宏閣,饒志仁,施際武;大鼠孤束迷走復(fù)合體兒茶酚胺能神經(jīng)元向杏仁核的直接投射—HRP與免疫組織化學(xué)雙標(biāo)記研究[J];神經(jīng)解剖學(xué)雜志;1992年02期

5 康頌建;孤束核內(nèi)的神經(jīng)遞質(zhì)及其生理作用[J];生理科學(xué)進(jìn)展;1992年01期

6 王惠元,金秀吉,杜一凡,李基俊,陳鋼;電刺激大鼠藍(lán)斑核對尿量的影響[J];生理學(xué)報;1987年01期

7 徐浩東,黃偉秋,趙薇薇,徐斌,于志銘;中樞去甲腎上腺素能系統(tǒng)對大鼠頸動脈竇反射的影響[J];生理學(xué)報;1992年02期

8 郭涓,殷偉平,黃偉秋,徐斌,錢忠明;大鼠杏仁中央核內(nèi)注射CRH對血壓的影響及其中樞機制初探[J];生理學(xué)報;1997年01期

9 王國卿;孫萬平;鄒容;李金華;周希平;;藍(lán)斑H_1受體作用參與腦室注射組胺對頸動脈竇反射的重調(diào)定[J];蘇州大學(xué)學(xué)報(醫(yī)學(xué)版);2005年06期

10 王國卿,周希平,蔣星紅,沈新娥,張玉英;中樞α受體在腦室注射組胺對頸動脈竇反射重調(diào)定中的作用[J];中國藥理學(xué)通報;2003年09期

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