發(fā)布時(shí)間：2018-06-07 02:00

  本文選題：中腦導(dǎo)水管周圍灰質(zhì)腹外側(cè)區(qū) + 電針耐受　； 參考：《遵義醫(yī)學(xué)院》2017年碩士論文

【摘要】：NMDA受體(N-甲基-D-天冬氨酸受體,N-methyl-D-aspartate receptor)是離子型谷氨酸受體的一個(gè)亞型,在中樞神經(jīng)系統(tǒng)發(fā)育及多種神經(jīng)系統(tǒng)疾病中發(fā)揮重要的生理及病理功能。NMDA受體NR1亞基上存在“甘氨酸位點(diǎn)(glycine site)”,該位點(diǎn)被甘氨酸結(jié)合后,谷氨酸(glutamic acid)才能有效開放NMDA受體偶聯(lián)的離子通道。多年研究顯示,D-絲氨酸(D-serine,D-Ser)才是NMDA受體NR1亞基“甘氨酸位點(diǎn)”的內(nèi)源性配體,D-Ser通過調(diào)節(jié)NMDA受體的激活參與機(jī)體多種生理及病理過程,其中包括痛覺信息的調(diào)制過程。針對中樞神經(jīng)系統(tǒng)D-Ser功能的研究近年已成為神經(jīng)科學(xué)領(lǐng)域研究的熱點(diǎn)之一。電針(electroacupuncture,EA)是將傳統(tǒng)針灸與電療相結(jié)合,進(jìn)而產(chǎn)生臨床鎮(zhèn)痛作用,但長時(shí)間或反復(fù)多次給予電針刺激,電針的鎮(zhèn)痛效應(yīng)會逐漸減低以致消失,表現(xiàn)為電針耐受(electroacupuncture tolerance,EA tolerance),限制其在臨床中的運(yùn)用。中腦導(dǎo)水管周圍灰質(zhì)(periaqueductal gray,PAG)是機(jī)體內(nèi)源性鎮(zhèn)痛系統(tǒng)的關(guān)鍵部位,特別是其腹外側(cè)區(qū)(ventrolateral periaqueductal gray,vl PAG),在疼痛調(diào)制和嗎啡耐受的形成、維持機(jī)制中均有重要作用。大量研究顯示,嗎啡耐受和電針耐受之間存在交叉耐受,但在vl PAG中D-Ser是否可以通過調(diào)節(jié)NMDA受體功能參與電針耐受的形成和維持機(jī)制,這一點(diǎn)未見文獻(xiàn)報(bào)道。本研究旨在明確在vl PAG中D-Ser是否介入大鼠電針耐受的形成和維持機(jī)制。目的:觀察大鼠中腦導(dǎo)水管周圍灰質(zhì)腹外側(cè)區(qū)(vl PAG)中D-Ser在大鼠電針耐受形成和維持中的作用并探討其初步的中樞神經(jīng)化學(xué)機(jī)制。方法:SD大鼠外周穴位給予多次電針刺激后建立大鼠電針耐受模型;(1)觀察電針耐受大鼠機(jī)械痛閾(MWT)、熱痛閾(TWL)變化百分?jǐn)?shù)的改變;(2)ELISA法檢測大鼠在電針耐受形成前后vl PAG中D-Ser水平變化;(3)免疫組化、免疫印跡法檢測大鼠電針形成前后vl PAG中SR的表達(dá)部位及蛋白表達(dá)量的變化情況;(4)免疫組化法檢測大鼠電針耐受形成前后vl PAG中星形膠質(zhì)細(xì)胞活化的情況;(5)電針耐受大鼠vl PAG微量注射不同劑量的星形膠質(zhì)細(xì)胞抑制劑-氟代檸檬酸(Fc)后再行電針刺激,觀察大鼠MWT、TWL變化百分?jǐn)?shù)變化并檢測D-Ser水平變化情況。結(jié)果:在各觀察時(shí)間點(diǎn),假電針組大鼠MWT、TWL變化百分?jǐn)?shù)與正常組大鼠相比較,差異無統(tǒng)計(jì)學(xué)意義(P0.05);電針組大鼠MWT、TWL變化百分?jǐn)?shù)與正常組比較顯著升高(P0.001),但隨著電針刺激次數(shù)的增多,MWT、TWL變化百分?jǐn)?shù)逐漸下降,6次電針后MWT、TWL趨近于正常組痛閾變化百分?jǐn)?shù)值,P0.05,提示:大鼠電針耐受形成。同一時(shí)間點(diǎn),電針耐受大鼠vl PAG中D-Ser水平升高、SR陽性細(xì)胞數(shù)和SR蛋白含量表達(dá)上調(diào)(P0.001),且vl PAG中星形膠質(zhì)細(xì)胞活化表達(dá)量增多,與正常組、假電針組比較,差異具有統(tǒng)計(jì)學(xué)意義(P0.001);電針耐受大鼠vl PAG中微量注射不同劑量的Fc后再給予電針刺激,星型膠質(zhì)細(xì)胞活化受抑制,vl PAG中D-Ser水平下降,大鼠MWT、TWL變化百分?jǐn)?shù)升高,差異具有統(tǒng)計(jì)學(xué)意義(P0.001),提示大鼠電針耐受緩解。結(jié)論:vl PAG中星形膠質(zhì)細(xì)胞活化引起D-Ser釋放增加參與大鼠電針耐受機(jī)制。
[Abstract]:The NMDA receptor (N- methyl -D- aspartic acid receptor, N-methyl-D-aspartate receptor) is a subtype of the ionotropic glutamate receptor, which plays an important physiological and pathological function in the central nervous system and a variety of nervous system diseases. The "glycine acid site (glycine site)" exists on the NR1 subunit of the.NMDA receptor NR1, which is binding to glycine Then, glutamic acid (glutamic acid) can effectively open the ion channel coupled with NMDA receptor. Years of studies have shown that D- serine (D-serine, D-Ser) is the endogenous ligand of the NMDA receptor NR1 subunit "glycine site". D-Ser participates in various physiological and pathological processes by regulating activation of NMDA receptors, including modulation of pain information. The study of the D-Ser function of the central nervous system (CNS) has become one of the hot spots in the field of neuroscience in recent years. Electroacupuncture (EA) combines traditional acupuncture and electrotherapy with electrotherapy to produce clinical analgesic effect. However, electroacupuncture has been given for a long time or repeatedly, and the analgesic effect of electroacupuncture will gradually decrease and disappear. Electroacupuncture tolerance (EA tolerance), which restricts its application in clinical practice. The periaqueductal gray (PAG) around the mesencephalic aqueduct is the key part of the body's endogenous analgesic system, especially in the ventral lateral region (ventrolateral periaqueductal gray, VL PAG), in the form of pain modulation and morphine tolerance There is an important role in the maintenance mechanism. A large number of studies have shown that there is a cross tolerance between morphine tolerance and electroacupuncture tolerance, but whether D-Ser can be involved in the formation and maintenance of electroacupuncture tolerance by regulating NMDA receptor function in VL PAG is not reported in the literature. This study aims to determine whether D-Ser is involved in rat electricity in VL PAG. The formation and maintenance mechanism of needle tolerance. Objective: To observe the role of D-Ser in the formation and maintenance of electroacupuncture tolerance in rat mesencephalic periaqueductal gray matter (VL PAG) and to explore its primary central neurochemical mechanism. Methods: the rat electroacupuncture tolerance model was established after multiple electroacupuncture stimulation in the peripheral acupoints of SD rats; (1) observation of electricity. The needle tolerance of mechanical pain threshold (MWT) and thermal pain threshold (TWL) change percentage of rats; (2) ELISA method was used to detect the change of D-Ser level in VL PAG in rats before and after the formation of electroacupuncture tolerance; (3) immunoblotting and immunoblotting were used to detect the expression of SR in VL PAG before and after the formation of electroacupuncture in rats; (4) immuno histochemistry was used to detect large amounts. The activation of astrocytes in VL PAG before and after formation of rat Electroacupuncture; (5) electroacupuncture tolerance rats VL PAG microinjection of different doses of astrocyte inhibitor - fluorocitric acid (Fc) after electroacupuncture stimulation, observe the change of MWT and TWL changes in rats and examine the change of D-Ser level. Results: at each observation time point, false There was no significant difference in the change percentage of MWT and TWL in the electroacupuncture group with the normal group (P0.05). The percentage of MWT in the electroacupuncture group was significantly higher than that in the normal group (P0.001), but with the increase of the number of stimulation of the electroacupuncture, the percentage of MWT and TWL decreased gradually, and MWT after 6 times electroacupuncture, TWL reached a hundred of the normal group pain threshold. P0.05, suggested that the electroacupuncture tolerance of rats was formed. At the same time point, the D-Ser level in the electroacupuncture tolerance rats increased in the VL PAG, the number of SR positive cells and the expression of SR protein up up (P0.001), and the activation expression of astrocytes in VL PAG increased, and the difference was statistically significant compared with the normal group and the false electroacupuncture group (P0.001); Electroacupuncture tolerance was large. Rat VL PAG was injected with different doses of Fc and stimulated by electroacupuncture, the activation of astrocytes was inhibited, D-Ser level in VL PAG decreased, the percentage of MWT and TWL in rats increased, the difference was statistically significant (P0.001), suggesting that the rat electroacupuncture tolerance remission. Conclusion: astrocyte activation in VL PAG leads to increased participation of astrocyte activation in D-Ser release. The mechanism of electroacupuncture tolerance in rats.
【學(xué)位授予單位】：遵義醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R245

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