【摘要】：目的： 研究GABAA受體γ2亞基和α2亞基在神經(jīng)病理性痛(Chronic Constriction Injury, CCI)大鼠DRG神經(jīng)元上的表達(dá)，以及巴氯芬干預(yù)后在CCI模型大鼠背根神經(jīng)節(jié)(Dorsal RootGganglion, DRG)神經(jīng)元上GABAA受體的功能和GABAA受體γ2亞基表達(dá)的變化。 方法： (1)制備SD大鼠CCI模型，其中部分模型鼠以灌胃方式給予巴氯芬干預(yù)；(2)熱板實(shí)驗(yàn)檢測(cè)給予巴氯芬干預(yù)前后CCI模型鼠熱刺激縮足反射潛伏期(Thermal WithdrawalLatency, TWL)；(3)膜片鉗技術(shù)觀察CCI模型組及巴氯芬干預(yù)組，DRG神經(jīng)元上GABAA受體介導(dǎo)的內(nèi)向電流的變化；(4)應(yīng)用Western Blot技術(shù)檢測(cè)CCI組及巴氯芬組GABAA受體γ2亞基表達(dá)變化；(5)應(yīng)用免疫熒光化學(xué)技術(shù)檢測(cè)CCI術(shù)后GABAA受體α2亞基的在DRG神經(jīng)元上的表達(dá)分布情況。 結(jié)果： (1) CCI模型大鼠的TWL比正常組明顯縮短，，給予巴氯芬干預(yù)后大鼠TWL逐漸延長(zhǎng)，至一周趨近于正常(p 0.05, n=10/group)；(2)膜片鉗實(shí)驗(yàn)發(fā)現(xiàn)CCI手術(shù)后，手術(shù)側(cè)組GABAA受體介導(dǎo)的內(nèi)向電流較正常組明顯減小，對(duì)側(cè)組GABAA受體介導(dǎo)的內(nèi)向電流較正常組明顯增強(qiáng)；巴氯芬抑制DRG神經(jīng)元GABAA受體介導(dǎo)的內(nèi)向電流(p 0.05, n=6)；(3) WB檢測(cè)發(fā)現(xiàn)CCI手術(shù)側(cè)和手術(shù)對(duì)側(cè)DRG神經(jīng)元上GABAA受體γ2亞基的表達(dá)量較對(duì)照組明顯下調(diào)，但是磷酸化GABAA受體γ2亞基表達(dá)量明顯上調(diào)(p 0.05, n=6)；(4)WB檢測(cè)發(fā)現(xiàn)巴氯芬干預(yù)組的GABAA受體γ2亞基表達(dá)較CCI組進(jìn)一步下調(diào)，磷酸化的GABAA受體γ2亞基表達(dá)較CCI組進(jìn)一步上調(diào)；(5)免疫熒光顯示CCI術(shù)側(cè)組GABAA受體α2亞基表達(dá)量較正常組下調(diào)，對(duì)側(cè)組表達(dá)量上調(diào)(p 0.05, n=6)。 結(jié)論： 神經(jīng)病理性痛狀態(tài)下，GABAA受體γ2亞基參與痛覺的形成過程，巴氯芬作為GABAB受體的激動(dòng)劑，通過增加GABAA受體γ2亞基的磷酸化水平抑制GABAA受體的功能。
[Abstract]:Objective: to study the expression of GABAA receptor 緯 2 subunit and 偽 2 subunit in DRG neurons of (Chronic Constriction Injury, CCI) rats with neuropathic pain and (Dorsal RootGganglion, in dorsal root ganglion of CCI model rats after the intervention of baclofen. The function of GABAA receptor and the expression of GABAA receptor 緯 2 subunit in DRG neurons. Methods: (1) the CCI model of SD rats was established, and some of them were treated with baclofen by gavage; (2) the latent period of thermal stimulation of paw reflex was detected by hot plate test in CCI model rats before and after the treatment with baclofen. (3) the changes of inward currents mediated by GABAA receptor in DRG neurons were observed by patch clamp technique in CCI model group and baclofen intervention group, (4) the expression of GABAA receptor 緯 2 subunit in CCI group and baclofen group were detected by Western Blot technique. (5) Immunofluorescence technique was used to detect the expression of GABAA receptor 偽 2 subunit in DRG neurons after CCI. Results: (1) the TWL of the CCI model rats was shorter than that of the normal group. The TWL of the rats treated with baclofen was prolonged gradually and reached to the normal level in one week (p 0.05, n=10/group). (2) after CCI operation, the inward current mediated by GABAA receptor in the operation side group was significantly lower than that in the normal group, and the inward current mediated by the GABAA receptor in the contralateral group was significantly higher than that in the normal group. Baclofen inhibited inward currents mediated by GABAA receptor in DRG neurons (p0.05, nong6). (3) WB showed that the expression of GABAA receptor 緯 2 subunit was significantly down-regulated in the DRG neurons of the operative and contralateral sides of CCI compared with the control group, but the expression of phosphorylated GABAA receptor 緯 2 subunit was significantly up-regulated (p 0.05, nong 6). (4) the expression of GABAA receptor 緯 2 subunit was further down-regulated and phosphorylated GABAA receptor 緯 2 subunit expression was further up-regulated in baclofen intervention group than in CCI group. (5) Immunofluorescence showed that the expression of GABAA receptor 偽 2 subunit was down-regulated in CCI side group and up-regulated in contralateral group (p 0.05, nong 6). Conclusion: in neuropathic pain state, GABAA receptor 緯 2 subunit is involved in the formation of pain. As an agonist of GABAB receptor, baclofen inhibits the function of GABAA receptor by increasing the phosphorylation level of GABAA receptor 緯 2 subunit.
【學(xué)位授予單位】：石河子大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R741

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