术后盐酸氢吗啡酮和吗啡镇痛对肝癌大鼠肝叶切除术后外周血Tregs及NK细胞的影响

THE EFFECT OF POSTOPERATIVE HYDROMORPHONE AND MORPHINE ANALGESIA ON PERIPHERAL BLOOD TREGS AND NK CELLS IN RAT HEPATOCELLULAR CARCINOMA SURGICAL MODEL

摘要:

目的：检测肝癌大鼠肝叶切除术后盐酸氢吗啡酮或吗啡镇痛对其外周血调节性T细胞(regulatory T cells, Tregs)、自然杀伤细胞(natural killer cells, NK)水平的影响。 方法：45只SD大鼠经二乙基亚硝胺(Diethyl Nitrosamine, DENA)诱导出肝癌后随机分成生理盐水组（NS组）、吗啡组（M组）和氢吗啡酮组（H组），（n=15/组）。3组大鼠行肝叶切除手术后分别经腹腔微量给药渗透压泵给予生理盐水、吗啡、盐酸氢吗啡酮镇痛，持续三天。用vonfrey检测腹部切口旁机械性痛觉阈值（Mechanical pain threshold，MPT）变化。用流式细胞技术检测其循环中Tregs及NK细胞占外周血单个核细胞百分比（Peripheral blood mononuclear cells，PBMCs）。用HE染色明确肝癌情况。结果：和NS组相比，H组和M组在术后1、3、7天的MPT评分更高（P＜0.05）； 但H组和M组之间无显著差别（P＞0.05）。与术前相比，三组大鼠术后第3、7天的Treg细胞百分比均升高（P＜0.05），NK细胞百分比均降低（P＜0.05)。和NS组相比，H组和M组在术后3、7天时Treg细胞百分比更低（P＜0.05），而NK细胞占比更高（P＜0.05）。在术后第7天时，和M组比，H组Treg细胞百分比更低（P＜0.05），NK细胞占比更高（P＜0.05）。结论：术后盐酸氢吗啡酮和吗啡镇痛都可减少外周血Treg细胞占PBMCs的百分比并增加NK细胞占PBMCs的百分比，而且盐酸氢吗啡酮的作用更强。

Abstract:

Objective: Our present study aims to detect the effects of hydromorphone or morphine analgesia on the levels of Tregs and NK cells in the peripheral blood of HCC rats after hepatectomy. Methods: 45 SD rats were induced by Diethyl Nitrosamine (DENA) to become liver cancer rats, then they were randomly divided into three groups: normal saline group (group NS), morphine group (group M) and hydromorphone group (group H)（n=15/group）. After liver lobectomy, rats were given normal saline, morphine, and hydromorphone by osmotic pump for 3 days. Changes in the Mechanical pain threshold (MPT) near the abdominal incision were detected by vonfrey. Flow cytometry (FCM) was used to detect the percentage of Tregs and NK in peripheral blood mononuclear cells (PBMCs). Modeling was successful when Hepatocellular carcinoma cells was observed by HE staining. Results: Compared with group NS, the MPT of group M and group H was significantly higher at 1, 3 and 7 days after surgery (P<0.05), but no statistical difference was found between group M and group H (P >0.05). The percentage of Treg cells was increased (P < 0.05) and the percentage of NK cells was decreased (P < 0.05) at 3 days and 7 days after surgery compared with that before surgery. Compared with group NS, the Tregs of group M and group H were lower and the NK cells were higher at 3 and 7 days after surgery (P<0.05). Tregs of group H were significantly lower and the NK cells were higher than those of group M at 7 days after surgery (P<0.05). Conclusion: Both hydromorphone and morphine for postoperative analgesia can down-regulate the percentage of Treg cells and up-regulate the percentage of NK cells in peripheral blood after surgery, and the effect of morphine hydrochloride is stronger.