一种新型N-型电压敏感性钙通道拮抗剂虎纹蜘蛛毒素-I对大鼠内脏痛模型镇痛作用的研究  

Analgesic effect of huwentoxin-I, a new N-type voltage-sensitive calcium channel blocker, on acute visceral pain in rats

作　　者：陈嘉勤[1] 陈威华[1] 邓梅春[2] 黎冠[2] 康园[1] 丁振华[3] 梁宋平[2] 

机构地区：[1]湖南师范大学体育学院,湖南长沙410081 [2]湖南师范大学生命科学院,湖南长沙410081 [3]南方医科大学热卫系,广东广州510515

出　　处：《第一军医大学学报》2005年第1期10-14,共5页Journal of First Military Medical University

基　　金：国家自然科学基金(39370152);国家"863"计划资助项目(103-13-01-06)~~

摘　　要：目的研究一种新型N-型电压敏感性钙通道拮抗剂虎纹蜘蛛毒素-Ⅰ(HWAP-I)经蛛网膜下腔用药对福尔马林诱导的大鼠急性炎性内脏疼痛的抑制作用.方法福尔马林快速注入SD大鼠乙状结肠壁粘膜下层作为疼痛模型,以数种可评估的反映内脏疼痛的固定性行为作为疼痛评分指标(疼痛分数).此前30 min经留置的导管注射各待测试剂于蛛网膜下腔内,以观察其对该模型疼痛行为的作用.结果以生理盐水阴性对照组和美国同类镇痛新药SNX-111(0.2,0.5和0.75μg/kg·b.w.)和盐酸吗啡(0.05,0.1和0.2μg/kg·b.w.)两个阳性对照组比较,HWAP-I(0.1～1.0μg/kg·b.w.)均能以剂量依赖方式明显抑制福尔马林结肠壁粘膜下注射所诱导的大鼠急性伤害性行为反应.HWAP-I和SNX-111在0.2μg/kg·b.w.时即有稳定和明显的疼痛抑制作用.虽然在同等剂量时SNX-111镇痛效果略大于HWAP-I,但在≥0.5μg/kg·b.w.的较高剂量时SNX-111会引起大鼠产生明显的运动能力障碍,而HWAP-I在此剂量范围内则未见明显的这类毒副作用.盐酸吗啡镇痛作用起效快于HWAP-I和SNX-111,但维持时间较后二者短.结论作为一种新型的多肽类N-型电压敏感性钙通道拮抗剂,HWAP-I和其类似物SNX-111经蛛网膜下腔用药后,对结肠壁粘膜下注射福尔马林引起的大鼠急性炎性内脏疼痛具有和盐酸吗啡类似的、剂量依赖性抑制作用,且维持时间更长.Objective To study the antinociceptive effect of intrathecally administered huwentoxin-I (HWTX-I or HWAP-I) on visceral pain in rats with acute colon inflammation. Methods Nociceptive behaviors was induced by formalin injected into the submucosa of the sigmoid colon in rats and the typical behavioral patterns induced served as the indexes for visceral nociception scoring. HWAP-I (0.1-1.0 μg/kg·b.w.), SNX-111 (0.2, 0.5 and 0.75 μg/kg·b.w.) and morphine hydrochloride (0.05, 0.1 and 0.2 μg/kg·b.w.) were administered subarachnoidally 30 min before formalin injection. Results Similar to SNX-111 and hydrochloride morphine, HWAP-I administered subarachnoidally significantly reduced nociceptive responses in a dose-dependent manner in the rat model of visceral pain (P<0.05). Both HWAP-I and SNX-111produced pain suppression effect at the dosage of 0.2 μg/kg·b.w., and in spite of the stronger antinociceptive effect of SNX-111 than HWAP-I at the same doses, SNX-111 caused obvious motor dysfunction in the rats at the doses higher than 0.5 μg/kg·b.w., which was not observed with HWAP-1 at such doses. The antinociceptive effect of morphine hydrochloride was initiated faster but lasted for a shorter period of time than the effects of HWAP-I and SNX-111. Conclusion As a potent blocker of neuronal N-type voltage-sensitive calcium channel, HWAP-I induces remarkably dose-dependent inhibitory effect similar to SNX-111 and morphine on visceral pain induced by sigmoid colon submucosal injection of formalin in conscious rats.

关 键 词：虎纹毒素-Ⅰ(HWTX—Ⅰ or HWAP—Ⅰ) N-型电压敏感性钙通道 钙通道拮抗剂 内脏痛 镇痛 

分 类 号：R96[医药卫生—药理学]