吗啡对小鼠血清IL-6和NK细胞活性的影响

Effects of morphine on serum IL-6 concentration, NK cell activity and cAMP content of spleen cell in mice

目的 探讨不同剂量吗啡对小鼠血清IL 6、NK细胞活性的影响。方法 选择BABL/C小鼠 ,随机分组。第一部分为 6组 ,其中 4组分别注射不同剂量的吗啡 ,另 2组为完全空白对照组 ,生理盐水对照组。第二部分将小鼠分为 5组 ,1～ 4组先注射不同剂量纳洛酮 ,15min后每组半数小鼠注射吗啡 (30mg/kg) ,余下的半数小鼠注射生理盐水。第 5组是小鼠先注射吗啡 (30mg/kg) ,15min后注射纳洛酮 (1mg/kg)。检测血清IL 6、NK细胞活性、脾细胞cAMP含量。 结果 第一部分 :与对照组相比 :①腹腔注射吗啡 10 0mg/kg使IL 6明显增加 ;② 3mg/kg吗啡即可使小鼠的NK细胞活性明显降低 ;③腹腔注射吗啡 30mg/kg、10 0mg/kg使小鼠cAMP明显降低。第二部分 :①注射纳洛酮和吗啡与同浓度纳洛酮加生理盐水组相比 ,IL 6含量没有明显改变 ;②纳洛酮 0 1mg/kg不能拮抗吗啡NK细胞活性的抑制 ;而纳洛酮 1 0mg/kg ,10mg/kg能增加NK细胞的活性 ,但与对照组相比没有明显差别 ;③纳洛酮 1 0mg/kg ,10mg/kg可拮抗吗啡对cAMP的抑制作用 ;④不同注射顺序吗啡和纳洛酮的对IL 6和cAMP无影响 ,但先注射吗啡 ,后注射纳洛酮对NK活性的抑制较轻。结论 吗啡对小鼠的免疫功能有调节作用 ,大剂量使IL 6含量明显增加 ,纳洛酮没有明显的拮抗作用 ;

Objective The study consisted of two parts In the first part the effects of different doses of morphine on cell mediated immune response (CMIR) were examined In the second part the effects of naloxone on CMIR and morphine induced alteration in CMIR were investigated Methods BABL/C mice were used for the study In the first part 36 mice were divided into 6 groups of 6 mice each: group 1 served as blank control, group 2 received normal saline, group 3 6 received morphine 3mg/kg, 10mg/kg, 30mg/kg and 100mg/kg intraperitoneally (ip) every day for three days In the second part 46 mice were divided into 5 groups: group 1 (n=10) received naloxone 0 mg/kg ip, group 2 (n=10) 0 1mg/kg, group 3 (n=10) 1 0mg and group 4 (n=10) 10mg/kg ip every day for three days 15min after naloxone injection half number of mice received morphine 30mg/kg and the other half normal saline In group 5 (n=6) the sequence of naloxone and morphine injection was reversed, morphine 30mg/kg was injected ip first and 15min later naloxone 1 0mg/kg was given ip 60min after last injection blood samples were taken from orbit for determination of serum IL 6 and NK cell activity, then the animals were sacrificed and spleen was removed and spleen cells were harvested for determination of cAMP content Results In the first part of the study ① intraperitoneal morphine 100mg/kg significantly increased serum IL 6 level (P<0 01) which was not affected by smaller doses ② morphine 3mg/kg reduced NK activity significantly and there was a linear negative correlation between doses of morphine and NK activity (r= 0 741) ③ Intraperitoneal morphine 30 mg/kg and 100 mg/kg significantly reduced cAMP content of spleen cell In the second part ① there was no significant difference in serum IL 6 level between naloxone+NS and naloxone+morphine ② Naloxone 0 1 mg/kg did not antagonize inhibition of NK activity by morphine but naloxone 1 0 mg/kg and 10 mg/kg did ③ Naloxone 1 0 mg/kg and 10 mg/kg antagonized the effect of morphine on cAMP content of spleen cell ④ Serum IL 6 concentration and cAMP content of spleen cell were not affected differently by the inverse order of naloxone and morphine injection Conclusions Morphine can modulate cell mediated immune function Some are enhanced and others inhibited Caution should be exercised when opioid like morphine, pethidine and fentanyl are used especially in immune function compromised patients