鞘内注射甘珀酸对佐剂性关节炎大鼠的抗伤害作用研究.docVIP

鞘内注射甘珀酸对佐剂性关节炎大鼠的抗伤害作用研究 苏州大学附属第一医院麻醉科 215006 侯永恒，杨建平，张慧娟，成浩，王丽娜 研究鞘内注射缝隙连接阻滞剂－甘珀酸（CBX）对佐剂性关节炎大鼠的抗伤害作用。　对所有大鼠L4-5鞘内置管，5～7后保留无障碍者。 行为学研究：成年雄性大鼠40只随机平分为五组，在大鼠左后肢踝关节外侧皮下注射完全弗氏佐剂（CFA）50μl建立佐剂性关节炎模型，分别以CBX 0（NS对照）、25、50和100μg的剂量在致炎后0.5h、1d、3d、5d、7d、10d、14d鞘内注射，每次给药后2h测定双侧PWTL。 形态学研究：15只雄性大鼠随机分为3组，每组5只。NS对照组大鼠左后肢踝关节外侧皮下注射NS 50μl，其它组注射CFA50μl，3d后NS对照组和CFA模型组鞘内注射NS 20μl；CBX处理组鞘内注射注射CBX100μg（20μl）。鞘内给药后2h，取脊髓腰膨大行c-免疫组织化学染色分析并FLIN计数。　1、单侧踝关节外侧皮下注射CFA可以在致炎后2h～7d诱导出双侧的热痛觉过敏，呈现明显的域外痛和镜像痛现象。鞘内注射CBX可以在炎性痛的不同阶段逆转这种痛阈改变（P0.05或0.01）。2、单侧踝关节外侧皮下CFA致炎后的第3天腰段脊髓双侧背角c- 蛋白表达显著增加，表现为致炎后FLI神经元数量增加和体积增大。而这种改变可以被鞘内注射甘珀酸逆转，与CFA组比较差异具有显著统计学意义（P0.01）。　结果证实甘珀酸，作为一种缝隙连接阻滞剂，对大鼠佐剂性关节炎诱导的病理性疼痛（包括域外痛和镜像痛）具有显著的抗伤害作用，提示缝隙连接可能参与炎性疼痛的中枢敏感化过程。 【关键词】 佐剂性关节炎; 炎性痛；缝隙连接; 甘珀酸；脊髓背角；c-蛋白 Antinociceptive Effects of Intrathecal Carbenoxolone on Adjuvant Arthritis Rats Objective To investigate the antinociceptive effects of intrathecal carbenoxolone (CBX), a gap junction blocker, on adjuvant arthritis rats. Methods Chronic lumbar intrathecal catheters were implanted and then confirmed in all rats. 1) Animal behavior research：40 rats were randomly divided into 4 groups. Adjuvant arthritis model was produced by inoculation of complete Freud’s adjuvant (CFA) at outer side of left ankle joint. Four doses of CBX (0, 25, 50, 100μg) were respectively administered in 4 groups at 0.5h, 1d, 3d, 5d, 7d, 10d, 14d post-CFA. Bilateral PWTL was measured at 2h after each drug delivery. 2) Morphological study: 15 male rats were randomly divided into 3 groups (n=5). NS control group rats were given hypodermic injection of NS 50μl at outer side of left ankle joint, whereas others were given CFA 50 μl inoculation. 3d later, NS control group and CFA group rats were given intrathecal injection of NS 20 μl, and CBX group CBX 100μg (20 μl). 2 h after every drug delivery, spinal intumescentia lumbalis were taken to conduct c-fos immunohistochemistry staining analysis and FLIN counting. Results 1) CBX could reverse periphery CFA-induced ther