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TRPV1下調(diào)對(duì)神經(jīng)病理性疼痛的保護(hù)作用及其作用機(jī)制研究

發(fā)布時(shí)間:2018-06-15 06:45

  本文選題:神經(jīng)病理性疼痛 + 辣椒素受體; 參考:《福建醫(yī)科大學(xué)》2014年碩士論文


【摘要】:目的:研究辣椒素受體(TRPV1)在大鼠創(chuàng)傷性神經(jīng)病理痛中的表達(dá)變化與作用;探討TRPV1拮抗劑是否有助于減輕疼痛。TRPV1的下調(diào)是否通過再生基因(PAP-I)起作用; 方法:將75只SD雄性大鼠(180g-220g)隨機(jī)分為假手術(shù)組、試驗(yàn)組A與實(shí)驗(yàn)組B,A、B兩組根據(jù)術(shù)后時(shí)間點(diǎn)再細(xì)分為7組(術(shù)前1d,1d,3d,5d,7d,14d,21d,n=5)。建立坐骨神經(jīng)慢性壓迫性損傷模型(CCI)[1]。B組在術(shù)后每天用TRPV1特異性拮抗劑SB705498(30mg/kg)灌胃給藥。A、B兩組在各實(shí)驗(yàn)預(yù)期時(shí)間點(diǎn)用Von frey針絲刺激大鼠術(shù)側(cè)趾蹼進(jìn)行痛閾值檢測(cè),隨后處死大鼠取L4-L5段脊髓的背根神經(jīng)節(jié)分別用免疫組化,RT-PCR,Western-blot等方法測(cè)量TRPV1及PAP-I的表達(dá)水平,記錄并分析兩者與神經(jīng)行為改變之間的相關(guān)性。 結(jié)果: CCI模型可明顯致大鼠機(jī)械痛敏,PAP-I在A、B兩組表達(dá)無統(tǒng)計(jì)學(xué)意義(P>0.05),術(shù)后第1d兩組即有表達(dá),在術(shù)后5d達(dá)到峰值,持續(xù)14d逐漸恢復(fù)到正常水平。假手術(shù)組TRPV1表達(dá)與A組術(shù)前無明顯差異(P>0.05),術(shù)后有統(tǒng)計(jì)學(xué)差異(P<0.05),A組TRPV1在術(shù)后開始表達(dá)并在第7d達(dá)到高峰,在3w后表達(dá)恢復(fù)到正常水平,其表達(dá)情況與痛閾值成正相關(guān)(r=0.79);B組給予其特異性拮抗劑后TRPV1表達(dá)較A組明顯降低(P<0.05),大鼠神經(jīng)痛的癥狀得到顯著改善。 結(jié)論:TRPV1參與神經(jīng)病理性疼痛的形成,應(yīng)用TRPV1特異性拮抗劑SB705498有助于改善神經(jīng)痛的癥狀。PAP-I在神經(jīng)病理性疼痛的發(fā)生發(fā)展過程中表達(dá)上升,,表達(dá)越程度越高,疼痛越明顯。阻斷TRPV1并不會(huì)對(duì)PAP-I表達(dá)造成影響。
[Abstract]:Objective: to investigate the expression and role of capsaicin receptor TRPV1 in traumatic neuropathic pain in rats, and to explore whether the down-regulation of TRPV1 may play a role in alleviating the pain by regeneration gene PAP-I. Methods: 75 Sprague-Dawley male rats were randomly divided into sham-operation group (n = 75). Group A and group B were subdivided into 7 groups according to the postoperative time points. To establish the model of chronic compression injury of sciatic nerve (CCI) [1]. Group B was given intragastric administration of TRPV1 specific antagonist SB70549830mg / kg every day after operation. The expression of TRPV1 and PAP-I in dorsal root ganglion (DRG) of L4-L5 spinal cord were measured by immunohistochemical RT-PCR and Western-blot respectively. The correlation between the expression of TRPV1 and PAP-I was recorded and analyzed. Results: the expression of PAP-I in the two groups was not statistically significant (P > 0.05). The expression of PAP-I in the first day after operation reached the peak value on the 5th day after operation, and gradually returned to the normal level on the 14th day. There was no significant difference in the expression of TRPV1 between group A and group A before operation (P > 0.05), but there was significant difference between group A and group A (P < 0.05). The expression of TRPV1 in group A began to express after operation and reached its peak on the 7th day. The expression of TRPV1 returned to normal level after 3 weeks. The expression of TRPV1 was positively correlated with the pain threshold. The expression of TRPV1 in group B was significantly lower than that in group A (P < 0.05), and the symptoms of neuralgia were significantly improved. ConclusionTwo one TRPV1 is involved in the formation of neuropathic pain. The application of TRPV1 specific antagonist SB705498 can improve the symptoms of neuralgia. The expression of PAP-I in the process of neuropathic pain is increased. The higher the expression, the more obvious the pain. Blocking TRPV1 did not affect the expression of PAP-I.
【學(xué)位授予單位】:福建醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2014
【分類號(hào)】:R741


本文編號(hào):2021085

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