左旋精氨酸及左旋精氨酸脱羧酶抗血清对吗啡镇痛及耐受的影响

EFFECTS OF L-ARGININE AND ANTI-L-ARGBSINE DECARBOXYLASE ANTIBODY ON MORPHINE ANALGESIA AND TOLERANCE

目的:分析左旋精氨酸及左旋精氨酸脱羧酶(L-ADC)对吗啡镇痛及其所致耐受的影响。方法:用家兔制备L-ADC多克隆抗体;以小鼠热辐射甩尾法和小鼠55℃热板测痛模型分析此抗体及左旋精氨酸对吗啡镇痛和耐受的影响。结果:在热辐射甩尾和热板测痛模型中,0.5-50mg·kg^(-1)的左旋精氨酸(sc)不影响吗啡镇痛和耐受(P>0.05)。L-ADC抗血清(脑室注射,1:1000-1:10稀释)能对抗吗啡镇痛作用,在热辐射甩尾和热板测痛模型中,它能使吗啡可能最大镇痛百分率分别从94.3％和80.6％下降到57.7％和42.9％(P<0.01)。吗啡连续处理小鼠3d后形成耐受:在热辐射甩尾和热板测痛模型中,吗啡的可能最大镇痛百分率分别从90.3％和80.3％下降到47.2％和40.5％;L-ADC抗血清能进一步加重吗啡所致耐受,其可能最大镇痛百分率进一步下降至19.8％和27.7％(P<0.01)。结论:L-ADC可能参与调节了吗啡镇痛及耐受形成过程;而左旋精氨酸不影响吗啡镇痛和耐受。

Objective: To analyse the effects of L-arginine and L-arginine decarboxylase (L-ADC) on morpinne analgesia and tolerance. Methods: Rabbit was used to prepare anti-L-arginine decarboxylase (anti-L-ADC) antibody. Then the effects of tins antibody (icv) and L-arginine (sc) on morpinne analgesia and tolerance were evaluated by heat radiation tail flick assay and 55C hot plate test in mice. Results: in the heat radiation tail flick assay and 55t hot plate test, subcuteneous injection of 0.5-50 mg kg-1 L-arginine didn't influence morpinne analgesia and tolerance (n = 10, P , 0.05). Anti-L-ADC antibody could antagonize morpinne analgesia; the possible maximum analgesia percent (PMAP) of morpinne reduced from 94.3% and 80.6% to 57.7% and 42.9% in the two models respectively after icv pre-treatment with the antibody (n = 10, P < 0.05). After the mice were treated with morpinne for 3 consecutive days, the PMAP of morpinne decreased from 90.3% and 80.3% to 47.2% and 40.5%, indicating the development of tolerance; co-administration of anti-L-ADC antibody with morpinne could further lower the PMAP of morpinne to 19.8% and 27.7% (n = 10, P <0.01). Conclusion : L-arginine decarboxylase might participate in morpinne analgesia and the developing process of tolerance to morpinne. L-arginine does not influence morpinne analgesia and tolerance.