虎纹蜘蛛毒素-Ⅰ对大鼠急性内脏疼痛的抑制性效应及与ω-芋螺毒素的比较研究(英文)  

Huwentoxin-I: Antinociceptive Effects and Its Comparison with ω-Conotoxin-MVIIA on Acute Visceral Pain in Rats

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

机构地区：[1]湖南师范大学生命科学学院,长沙410081

出　　处：《中国生物化学与分子生物学报》2005年第1期24-29,共6页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家"8 63"计划课题资助项目 (No .2 0 0 1AA2 15 2 41)~~

摘　　要：研究一种新型的N型电压敏感性钙通道阻断剂虎纹蜘蛛毒素 Ⅰ (HWTX Ⅰ ) ,硬脊膜外腔用药对福尔马林结肠壁粘膜下注射诱导的大鼠急性炎性内脏疼痛的抑制性效应 .5 %福尔马林溶液15 0 μl快速注入SD大鼠乙状结肠壁粘膜下层 ,可产生几种可评估的反映内脏疼痛的固定性行为 .在此伤害性刺激反应前 30min ,经留置的导管向大鼠硬脊膜外腔分别注入各待测药品和试剂 ,观察其对该模型疼痛行为的影响 .与生理盐水阴性对照组 ,美国同类镇痛新药ω 芋螺毒素 (ω CTX MVIIA)和吗啡两个阳性对照组比较 ,HWTX Ⅰ五个剂量组 ,进行大鼠硬脊膜外腔注药 ,均能以剂量依赖方式明显抑制福尔马林结肠壁注射诱导的伤害性行为反应 .HWTX Ⅰ和ω CTX MVIIA在 2 0μg kg体重剂量时 ,其抑制效果是稳定和明显的 ;在 5 0 70 μg kg体重剂量下 ,抑制效果更为显著 .HWTX Ⅰ量 效实验发现 ,在等剂量下 ,ω CTX MVIIA镇痛效果略高于HWTX Ⅰ .但在 5 0～ 75 μg kg较高剂量下 ,ω CTX MVIIA可能引起大鼠产生明显的运动能力障碍 ,而HWTX Ⅰ在该剂量范围内则未见类似的毒副作用 .盐酸吗啡镇痛作用起效快于HWTX Ⅰ和ω CTX MVIIA ,但维持时间较后二者短 .实验结果表明 :同为多肽类N型电压敏感性钙通道拮抗剂 ,HWTX Ⅰ和ω CTX MVIIA大鼠硬脊?The antinociceptive effect of epidural administration of huwentoxin I was elucidated in a tonic visceral pain rat model produced by acute colon inflammation. The nociceptive behaviors were induced by perendoscopically injecting dilute formalin (50 μl) into the depth of the colonic wall in rats. Both ω conotoxin MVIIA and morphine hydrochloride were given epidurally as positive control while saline as negative control. Similar to ω conotoxin MVIIA and hydrochloride morphine, the epidural administration of HWTX Ⅰ significantly reduced the nociceptive responses in a dose dependent manner in tonic visceral pain rat model ( P <0 05). The suppression effects of both huwentoxin Ⅰ and ω conotoxin MVIIA at 20 μg/kg were kept steady compared with the saline group and reached their maximum effects at the doses of 50～75 μg/kg within 1 hour when the nociception had been observed. It was also found that at the same doses, huwentoxin Ⅰ was less effective in antinociception than ω conotoxin MVIIA. However, ω conotoxin MVIIA, but not huwentoxin Ⅰ, caused an obvious motor dysfunction at these doses. The action of morphine hydrochloride was initiated faster, but lasted for a shorter time than that of huwentoxin Ⅰ and ω conotoxin MVIIA. Thus, huwentoxin Ⅰ, a potent blocker of neuronal N type voltage sensitive calcium channels, induced a remarkable dose dependent restrain effect similar to ω conotoxin MVIIA and morphine on the tonic visceral pain produced by colonic wall injection of formalin in conscious rats.

关 键 词：虎纹蜘蛛毒素-Ⅰ ω-芋螺毒素(ω-CTX—MVIIA) N-型电压敏感性钙通道 内脏痛 抗伤害作用 大鼠模型 

分 类 号：R996[医药卫生—毒理学] R97[医药卫生—药学]