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右美托咪定减轻荷瘤小鼠围手术期应激的促肿瘤活性:一种心理生理干预的替代方法。

Dexmedetomidine alleviates the pro-tumor activity of perioperative stress in tumor-bearing mice: an alternative approach of psycho-physiological intervention.

作者信息

Xu Shanqing, Tang Yongzhong, Tong Jianbin

机构信息

Department of Anaesthesiology, Third Xiangya Hospital, Central South University, Changsha, China.

Hunan Province Key Laboratory of Brain Homeostasis, Third Xiangya Hospital, Central South University, Changsha, China.

出版信息

World J Surg Oncol. 2025 Mar 28;23(1):103. doi: 10.1186/s12957-025-03665-w.

Abstract

BACKGROUND

The immediate perioperative period (IPP) usually is highly stressful and has significant effects on the postoperative recurrence/metastasis of tumors. Effective methods for limiting the impact of the IPP on postoperative recurrence/metastasis of tumors remain scarce. We aimed to determine the effects of dexmedetomidine (DEX) treatment during the IPP on postoperative recurrence/metastasis of tumors and the stress response.

MATERIALS AND METHODS

The clinical perioperative setting was mimicked via tumor resection and perioperative restraint stress in tumor-bearing mice with or without DEX during the IPP. The stress response was assessed using stress hormone and interleukin (IL)-6 levels in peripheral blood. Tumor cell growth was measured via in vivo bioluminescent imaging, cell viability assay, wound-healing assay, and Western blotting.

RESULTS

In tumor-bearing mice, DEX during the IPP limited the growth of implanted tumor cells and stress response in a dose-dependent manner. The serum from mice without DEX promoted cultured tumor cell growth, which was alleviated by beta-adrenergic receptor blocker propranolol or IL-6 antibody. Relative to the serum from mice without DEX, the serum from mice with DEX had lower stress hormone and IL-6 levels, as well as weaker effects on tumor growth promotion. Dexmedetomidine supplementation during culture had no significant effects on tumor cells.

CONCLUSIONS

Dexmedetomidine alleviates the pro-tumor activity of perioperative stress in abdominal tumors.

摘要

背景

围手术期即刻(IPP)通常压力极大,对肿瘤术后复发/转移有显著影响。限制IPP对肿瘤术后复发/转移影响的有效方法仍然匮乏。我们旨在确定IPP期间右美托咪定(DEX)治疗对肿瘤术后复发/转移及应激反应的影响。

材料与方法

通过对荷瘤小鼠在IPP期间进行肿瘤切除和围手术期束缚应激,模拟临床围手术期情况,部分小鼠给予DEX,部分不给予。使用外周血中的应激激素和白细胞介素(IL)-6水平评估应激反应。通过体内生物发光成像、细胞活力测定、伤口愈合测定和蛋白质免疫印迹法测量肿瘤细胞生长。

结果

在荷瘤小鼠中,IPP期间的DEX以剂量依赖的方式限制植入肿瘤细胞的生长和应激反应。未给予DEX的小鼠血清可促进培养的肿瘤细胞生长,β-肾上腺素能受体阻滞剂普萘洛尔或IL-6抗体可减轻这种促进作用。相对于未给予DEX的小鼠血清,给予DEX的小鼠血清中应激激素和IL-6水平较低,对肿瘤生长促进的作用也较弱。培养期间补充右美托咪定对肿瘤细胞无显著影响。

结论

右美托咪定可减轻腹部肿瘤围手术期应激的促肿瘤活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1470/11951540/f5be6195b54a/12957_2025_3665_Fig1_HTML.jpg

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