坐骨神經(jīng)周圍注射可樂定對CCI大鼠促炎性細胞因子表達的影響

1、坐骨神經(jīng)周圍注射可樂定對CCI大鼠促炎性細胞因子表達的影響         11-01-16 16:10:00     作者：劉永峰楊承祥     編輯：studa20【摘要】  目的：觀察損傷坐骨神經(jīng)周圍注射可樂定對慢性坐骨神經(jīng)結(jié)扎模型(chronic constriction injury，CCI)大鼠促炎性細胞因子表達的影響，探討2-腎上腺素受體激動劑是否對已經(jīng)形成的神經(jīng)病理性疼痛產(chǎn)生作用。方法：雄性SD大鼠32只，隨機

2、分為4組，每組8只。Sham組：只分離皮膚、肌肉，不結(jié)扎坐骨神經(jīng);Sal組：形成CCI后注射生理鹽水組;Clo組：形成CCI后注射可樂定組;Clo+Yo組：形成CCI后注射可樂定和育亨賓組。在注射藥物3 d后急性處死動物，取患側(cè)脊髓L4、L5、L6背根神經(jīng)節(jié)采取全自動化學(xué)發(fā)光法檢測TNF-和IL-6濃度。結(jié)果：術(shù)后從7 d開始CCI大鼠脊髓背根神經(jīng)節(jié)TNF-和IL-6濃度有明顯增高。損傷坐骨神經(jīng)周圍注射可樂定能明顯抑制CCI引起的脊髓背根神經(jīng)節(jié)TNF-和IL-6的表達(P<0.01)。結(jié)論：損傷的坐骨神經(jīng)周圍注射可樂定可以降低促炎性細胞因子的表達。 【關(guān)鍵詞】  可樂定;外周注

3、射;CCI大鼠;神經(jīng)病理性疼痛;TNF-;IL-6AbstractObjictive: To assess the effect of perineural clonidine on the expression of TNF- and IL-6 in the rats with chronic constriction injury(CCI) in the sciatic nerve. Methods：Thirty-two male SD rats were randomly divided into four groups(18 for each):sham group, Sal grou

4、p (CCI+ saline), Clo group(CCI+clonidine) and Clo+Yo group(CCI+clonidine+ yohimbin). The rats were killed 3 days after the injection of medicine mentioned above and spinal cord DRG of L4,L5,L6 were taken for determining the concentration of TNF- and IL-6 of DRG in the rats with automatic luminescent

5、 technique. Results: The rats of CCI group demonstrated steady mechanical and heat hyperaglsia from the seventh day after the operation. There was a remarkable increase in the concentration of TNF-a and IL-6 in DRG from the 7th day after the operation. Perineural injection of clonidine could suppres

6、s the expression of TNF- and IL-6 caused by CCI in the DRG of CCI rats(P<0.01). Conclusion: Perineural injection of clonidine modulates proinflammatory cytokines expression in CCI rats.Key wordsClonidine; Perineural inject; CCI; Neuropathic pain; TNF-; IL-6神經(jīng)病理性疼痛(neuropathic pain)是指由于神經(jīng)系統(tǒng)受到損傷或產(chǎn)生

7、病變而導(dǎo)致的疼痛。病理生理學(xué)特點主要表現(xiàn)為痛覺的高反應(yīng)性,如痛覺過敏( hyperalgesia)、痛覺超敏(allodynia)及自發(fā)疼痛( spontaneous pain)等。神經(jīng)病理性疼痛不同于由于組織損傷而導(dǎo)致的急性疼痛,通常呈慢性，可持續(xù)數(shù)天或數(shù)月,是目前臨床治療的難點之一?？蓸范? clonidine)是2-腎上腺素受體激動劑,臨床上常用來治療高血壓。近年來發(fā)現(xiàn)它具有很好的緩解神經(jīng)病理性疼痛的作用，多用于鞘內(nèi)、靜脈注射或伍用其他藥物治療慢性疼痛。本實驗擬在經(jīng)典的神經(jīng)病理性疼痛模型CCI上，通過在結(jié)扎坐骨神經(jīng)產(chǎn)生痛敏后，在損傷神經(jīng)周圍注射可樂定，探索外周注射可樂定是否對已經(jīng)形成的疼

8、痛產(chǎn)生影響,并通過檢測促炎性細胞因子變化探索其可能參與的作用機制。1材料與方法1.1材料健康成年雄性Sprague-Dawley大鼠,體重(200±20) g，由廣東醫(yī)學(xué)實驗動物中心提供。動物置于(20±1) 和24 h晝夜循環(huán)的環(huán)境中，能夠自由地獲取水和食物。所有動物適應(yīng)環(huán)境3 d后投入實驗。鹽酸可樂定注射液(035K0846)、鹽酸育亨賓注射液(015K1444)以及TNF-、IL-6試劑盒均購自美國Sigma公司。1.2方法2結(jié)果2.1動物模型行為表現(xiàn)實驗期間，所有大鼠均保持良好狀態(tài)，無明顯傷口感染現(xiàn)象。Sham組大鼠活動如常。結(jié)扎坐骨神經(jīng)大鼠左側(cè)(結(jié)扎側(cè))出現(xiàn)舔爪、跛行，安靜時患足常保持防御姿勢?；紓?cè)足趾并攏并呈輕度外翻狀。注射可樂定后，舔爪、跛行等行為減輕。2.2促炎性細胞因子變化3討論3.1神經(jīng)病理性疼痛模型對神經(jīng)病理性疼痛發(fā)病機制的研究大多來源于動物模型。Bennett和Xie等開發(fā)出的CCI模型與