CAJ | 학술논문

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150μl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30 min,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,HWTK-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20μg/kg体重剂量时,其抑制效果是稳定和明显的;在50,70μg/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50～75μg/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大鼠硬脊膜外腔用药,对结肠壁注射福尔马林引起的大鼠急性炎性内脏疼痛模型呈现出和盐酸吗啡类似的剂量依赖性抑制效应,且前二者维持时间较后者更长.
연구일충신형적N형전압민감성개통도조단제호문지주독소-Ⅰ(HWTX-Ⅰ),경척막외강용약대복이마림결장벽점막하주사유도적대서급성염성내장동통적억제성효응.5%복이마림용액150μl쾌속주입SD대서을상결장벽점막하층,가산생궤충가평고적반영내장동통적고정성행위.재차상해성자격반응전30 min,경류치적도관향대서경척막외강분별주입각대측약품화시제,관찰기대해모형동통행위적영향.여생리염수음성대조조,미국동류진통신약ω-우라독소(ω-CTX-MVIIA)화마배량개양성대조조비교,HWTK-Ⅰ오개제량조,진행대서경척막외강주약,균능이제량의뢰방식명현억제복이마림결장벽주사유도적상해성행위반응.HWTX-Ⅰ화ω-CTX-MVIIA재20μg/kg체중제량시,기억제효과시은정화명현적;재50,70μg/kg체중제량하,억제효과경위현저.HWTX-Ⅰ량-효실험발현,재등제량하,ω-CTX-MVIIA진통효과략고우HWTX-Ⅰ.단재50～75μg/kg교고제량하,ω-CTX-MVIIA가능인기대서산생명현적운동능력장애,이HWTX-Ⅰ재해제량범위내칙미견유사적독부작용.염산마배진통작용기효쾌우HWTX-Ⅰ화ω-CTX-MVIIA,단유지시간교후이자단.실험결과표명:동위다태류N형전압민감성개통도길항제,HWTX-Ⅰ화ω-CTX-MVIIA대서경척막외강용약,대결장벽주사복이마림인기적대서급성염성내장동통모형정현출화염산마배유사적제량의뢰성억제효응,차전이자유지시간교후자경장.
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-conotoxinMVIIA 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 huwentoxinⅠ , 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, huwentoxinⅠ , a potent blocker of neuronal N-type voltage-sensitive calcium channels, induced a remarkable dosedependent restrain effect similar to ω-conotoxin-MVIIA and morphine on the tonic visceral pain produced by colonic wall injection of formalin in conscious rats.