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长期术前血糖控制可恢复糖尿病小鼠围手术期中性粒细胞吞噬活性。

Long-term preoperative glycemic control restored the perioperative neutrophilic phagocytosis activity in diabetic mice.

机构信息

Division of Anesthesiology, Department of Surgery Related, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.

出版信息

BMC Endocr Disord. 2020 Sep 29;20(1):146. doi: 10.1186/s12902-020-00629-x.

Abstract

BACKGROUND

The risk of surgical site infection has been reported to be higher in patients with poorly controlled diabetes. Since chronic hyperglycemia impairs neutrophil functions, preoperative glycemic control may restore neutrophil function. However, long-term insulin therapy may lead to a delay in surgery, which may be a problem, especially in cancer surgery. It is therefore unfortunate that there have been few studies in which the optimal duration of perioperative glycemic control for diabetes with chronic hyperglycemia was investigated. Therefore, we investigated the effects of preoperative long-term insulin therapy and short-term insulin therapy on perioperative neutrophil functions in diabetic mice with chronic hyperglycemia.

METHODS

Five-week-old male C57BL/6 J mice were divided into four groups (No insulin (Diabetes Mellitus: DM), Short-term insulin (DM), Long-term insulin (DM), and Non-diabetic groups). Diabetes was established by administrating repeated low-dose streptozotocin. The Short-term insulin (DM) group received insulin therapy for 6 h before the operation and the Long-term insulin (DM) group received insulin therapy for 5 days before the operation. The No insulin (DM) group and the Non-diabetic group did not receive insulin therapy. At 14 weeks of age, abdominal surgery with intestinal manipulation was performed in all four groups. We carried out a phagocytosis assay with fluorescent microspheres and a reactive oxygen species (ROS) production assay with DCFH-DA (2',7'-dichlorodihydrofluorescein diacetate) before and 24 h after the operation using FACSVerse™ with BD FACSuite™ software.

RESULTS

Blood glucose was lowered by insulin therapy in the Short-term insulin (DM) and Long-term insulin (DM) groups before the operation. Neutrophilic phagocytosis activities before and after the operation were significantly restored in the Long-term insulin (DM) group compared with those in the No insulin (DM) group (before: p = 0.0008, after: p = 0.0005). However, they were not significantly restored in the Short-term insulin (DM) group. Neutrophilic ROS production activities before and after the operation were not restored in either the Short-term insulin (DM) group or Long-term insulin (DM) group.

CONCLUSIONS

Preoperative and postoperative phagocytosis activities are restored by insulin therapy for 5 days before the operation but not by insulin therapy for 6 h before the operation.

摘要

背景

有报道称,血糖控制不佳的患者发生手术部位感染的风险更高。由于慢性高血糖会损害中性粒细胞的功能,因此术前血糖控制可能会恢复中性粒细胞的功能。然而,长期的胰岛素治疗可能会导致手术延迟,这可能是一个问题,尤其是在癌症手术中。不幸的是,很少有研究探讨慢性高血糖糖尿病患者围手术期血糖控制的最佳时间。因此,我们研究了术前长期胰岛素治疗和短期胰岛素治疗对慢性高血糖糖尿病小鼠围手术期中性粒细胞功能的影响。

方法

将 5 周龄雄性 C57BL/6J 小鼠分为四组(无胰岛素组(糖尿病:DM)、短期胰岛素组(DM)、长期胰岛素组(DM)和非糖尿病组)。通过给予重复的小剂量链脲佐菌素建立糖尿病。短期胰岛素组(DM)在术前 6 小时接受胰岛素治疗,长期胰岛素组(DM)在术前 5 天接受胰岛素治疗。无胰岛素组(DM)和非糖尿病组未接受胰岛素治疗。在 4 组中,所有 4 组在 14 周龄时进行腹部手术伴肠操作。我们使用 FACSVerse™和 BD FACSuite™软件进行荧光微球吞噬试验和 DCFH-DA(2',7'-二氯二氢荧光素二乙酸酯)活性氧(ROS)产生试验,分别在术前和术后 24 小时进行。

结果

短期胰岛素(DM)组和长期胰岛素(DM)组在术前通过胰岛素治疗降低了血糖。与无胰岛素(DM)组相比,长期胰岛素(DM)组在术前和术后的中性粒细胞吞噬活性明显恢复(术前:p=0.0008,术后:p=0.0005)。然而,短期胰岛素(DM)组的恢复并不显著。短期胰岛素(DM)组和长期胰岛素(DM)组的中性粒细胞 ROS 产生活性在术前和术后均未恢复。

结论

术前和术后的吞噬活性通过术前 5 天的胰岛素治疗恢复,但术前 6 小时的胰岛素治疗则不能恢复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30e2/7525964/f16769d23ace/12902_2020_629_Fig1_HTML.jpg

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