比较盐酸羟考酮和吗啡对肝癌模型大鼠术后镇痛效应和免疫细胞的影响

Comparison of the effects of oxycodone hydrochloride and morphine on postoperative analgesia and immune cell in rats with liver cancer

目的比较盐酸羟考酮和吗啡对肝癌大鼠的术后镇痛效果及免疫细胞功能的影响。方法给予大鼠50 mg·kg^(-1)0.19%的二乙基亚硝胺(DENA)腹腔注射,每周2次,连续给药16周,直至肝癌模型构建成功。将18只模型大鼠随机分为阴性对照组(NC)、盐酸羟考酮组(OH组)及吗啡组(MO组),每组6只,进行腹腔探查术后,分别埋入装有生理盐水、盐酸羟考酮和吗啡的Alezt微量泵进行镇痛,分别于术后第1、3、7天进行糖水偏好实验、旷场实验(OFT),7天后心脏采血,流式细胞术检测外周血中NK细胞及Treg细胞百分比。结果与NC组相比,OH组和MO组大鼠糖水偏好率均显著升高(P<0.05);旷场试验中,OH组和MO组大鼠移动距离(P<0.05)及中央格持续时间明显增加(P<0.05);OH组大鼠糖水偏好率、旷场移动距离及中央格持续时间与MO组比较,差异均无统计学意义(P>0.05);OH组和MO组大鼠外周血Treg细胞比例均显著低于NC组(P<0.05),且OH组表现出比MO组更低的Treg细胞比例(P<0.05);OH组NK细胞比例显著高于NC组(P<0.05),而MO组NK细胞比例显著低于NC组(P<0.05)。结论盐酸羟考酮和吗啡在术后镇痛方面表现出类似效果,而盐酸羟考酮可显著抑制Treg细胞、增加NK细胞,从而增强机体抗肿瘤免疫功能,是更理想的围术期镇痛药物。

Objective To compare the effects of oxycodone hydrochloride and morphine on postoperative analgesia and immune cell function in rats with liver cancer.Methods The liver cancer model was successfully established by intraperitoneal injection of 0.19%diethylnitrosamine(DENA)at a dose of 50 mg·kg^(-1) and twice a week.18 rats were randomly divided into negative control group(NC),oxycodone hydrochloride group(OH)and morphine group(MO).After abdominal exploration,the rats were implanted with Alezt micro-pump containing normal saline,oxycodone hydrochloride and morphine for analgesia,respectively.On the 1st,3rd and 7th day after operation,the sucrose preference test and the open field test were performed.After 7 days,blood samples were collected from the heart.The proportion of NK cells and Treg cells in peripheral blood were detected by flow cytometry.Results Compared with NC group,the sucrose preference rate was significantly increased in OH group and MO group(P<0.05).Besides,the movement distance(P<0.05)and the time spent in central area(P<0.05)in OH group and MO group were significantly increased as compared with NC group.However,there were no significant differences between OH group and MO group in sucrose preference rate,movement distance and time spent in central area(P>0.05).Moreover,the proportion of Treg cells in OH group and MO group was significantly lower than that in the NC group(P<0.05),and OH group had a significantly lower proportion of Treg cells than MO group(P<0.05).The proportion of NK cells in OH group was significantly higher than that in NC group(P<0.05).On the contrary,the proportion of NK cells in MO group was significantly lower than that in NC group(P<0.05).Conclusion Oxycodone hydrochloride and morphine showed similar effects in postoperative analgesia.However,oxycodone hydrochloride could significantly improve the anti-tumor immune system by decreasing the proportion of Treg cells and increasing the proportion of NK cells.Oxycodone hydrochloride might be a more ideal analgesic drug than morphine during perioperative period.