CCK反义RNA及CCK受体拮抗剂L365，260使电针镇痛无效的大鼠转为有效  

ANTISENSE CCK RNA AND CCK_B RECEPTOR ANTAGONIST L365, 260 CHANGED NONRESPONDER RAT TO RESPONDER FOR ELECTROACUPUNCTURE ANALGESIA

作　　者：汤乃梅[1] 董宏伟[1] 张立新[1] 王晓民[1] 崔肇春 韩济生[1] 

机构地区：[1]北京医科大学神经科学研究中心,美国国立精神卫生研究院,大连医科大学生化教研室

出　　处：《中国疼痛医学杂志》1996年第2期103-108,共6页Chinese Journal of Pain Medicine

基　　金：国家自然科学基金;美国NIDA基金;香港北美医学基金

摘　　要：大鼠对电针刺激产生的镇痛反应，其程度随个体而异。多数为有效或强效者（ｒｅｓｐｏｎｄｅｒ），少数为弱效或无效者（ｎｏｎ－ｒｅｓｐｏｎｄｅｒ）。现有证据表明脑内八肽胆囊收缩素（ＣＣＫ－８）是一种强效的抗阿片物质，对电针镇痛起拮抗作用。本文发现侧脑室注射反义ＣＣＫ表达载体削弱脑内ＣＣＫ基因表达，可使大鼠对电针的反应由无效者变为有效者。皮下注射ＣＣＫＢ受体拮抗剂Ｌ３６５，２６０也有同样效果。这些结果说明，有可能通过抑制中枢ＣＣＫ的表达或阻断ＣＣＫ受体的功能，提高个体的电针镇痛效果。Wistar rats were given electrical stimulation via fine stainless steel needles inserted into the hind leg points, and tail flick latency was measured as endpoint of nociception.Most of the rats show an analgesic effect in response to electroacupuncture(EA) stimulation, designated as responders, as contrast to the non-responders which show no singnificant increase in pain threshold under the same stimulation. Previous studies have shown that cholecystokinin octapeptide(CCK-8) in the central nervus system is a potent anti-opioid substance which plays an antagonistic role on EA-induced analgesia. In this study we found that intracerebroventricular(icv) injection of antisense CCK vector encapsulated with lipofection to non-responder rat resulted in a potentiation of EA analgesia, i. e., changing non-responder into responder. This effect lasted for one week, and disappeared in 9 days.Control rats receiving empty plasmid pSV2-EP and lipofectin depicted a temporal augmentation of EA analgesia, which vanished after 4 days. The difference between pSV2-CCKAS+lipofectin group and pSV2-EP+lipofectin group was statistically very significant (P<0. 05 in day 4, P<0. 01 in day 6). Conversion from non-responder to responder could also be made possible by subcutaneous injection of CCKB receptor antagonist L365, 260. The results suggest that it is feasible to increase the efficacy of EA analgesia by suppressing CCK gene expression in CNS or by blockade of CCK receptor, thus changing non-responder into responder.

关 键 词：CCK-8 L365 260 反义核糖核酸 电针镇痛 

分 类 号：R441.1[医药卫生—诊断学]