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circRNA_102911/miR-129-5p/SOX6轴参与老年肝内胆管结石患者腹腔镜左肝切除术中T淋巴细胞免疫功能。

The circRNA_102911/miR-129-5p/SOX6 axis is involved with T lymphocyte immune function in elderly patients with laparoscopic left hepatectomy for hepatolithiasis.

作者信息

Zhao Hongqiang, Shao Xiaoyu, Liu Haorun, Liu Qi, Lu Jiangyang, Li Weimin

机构信息

Translational Medicine Research Center, Fourth Medical Center and Medical Innovation Research Division of the Chinese PLA General Hospital, Beijing 100048, P.R. China.

Department of Pathology, Fourth Medical Center of The Chinese PLA General Hospital, Beijing 100048, P.R. China.

出版信息

Exp Ther Med. 2021 Feb;21(2):150. doi: 10.3892/etm.2020.9582. Epub 2020 Dec 17.

Abstract

The aim of the present study was to investigate the impact of laparoscopic left hepatectomy (LLH) for hepatolithiasis on the T lymphocyte immune changes of elderly patients and to analyze underlying mechanisms of action behind these changes. A total of 164 patients who underwent LLH due to left-sided hepatolithiasis were recruited. In terms of T lymphocyte immune changes, it was found that firstly, the basic quantity of peripheral lymphocytes in the elderly group was significantly lower than that in a younger preoperative group. Secondly, after surgical trauma, the immune function of T lymphocytes had a significant decline and lasted longer when compared with younger patients, which was reflected by the perioperative changes in the T lymphocyte proliferative ability, levels of IL-2 secreted by T lymphocytes and the percentage of CD3/CD4 T lymphocytes in the peripheral blood. Circular RNA (circRNA) 102911 (102911) was upregulated and microRNA (miR)-129-5p was downregulated in CD3/CD4 T lymphocytes from elderly patients with LLH for hepatolithiasis. Furthermore, the overexpression of 102911 inhibited the proliferation of CD3/CD4 T lymphocytes as well as promoting cell apoptosis, with the opposite effects being observed on knockdown of 102911. miR-129-5p is involved in the proliferation and apoptosis of CD3/CD4 T lymphocytes and may be a promising target of 102911. Moreover, SOX6 is a downstream molecule of miR-129-5p. Immune function and number of T lymphocytes decreased significantly after surgical trauma compared to younger patients, and this decline lasted longer in older patients treated with LLH for hepatolithiasis. The 102911/miR-129-5p/SOX6 axis was found to be involved in T lymphocytes immune function, which provided a novel insight for the treatment of elderly patients with hepatolithiasis.

摘要

本研究旨在探讨腹腔镜左半肝切除术(LLH)治疗肝内胆管结石对老年患者T淋巴细胞免疫变化的影响,并分析这些变化背后的潜在作用机制。共招募了164例因左侧肝内胆管结石接受LLH的患者。在T淋巴细胞免疫变化方面,发现:首先,老年组外周淋巴细胞的基础数量显著低于术前较年轻组。其次,手术创伤后,与年轻患者相比,T淋巴细胞的免疫功能显著下降且持续时间更长,这通过T淋巴细胞增殖能力、T淋巴细胞分泌的IL-2水平以及外周血中CD3/CD4 T淋巴细胞百分比的围手术期变化得以体现。肝内胆管结石老年LLH患者的CD3/CD4 T淋巴细胞中,环状RNA(circRNA)102911(102911)上调,微小RNA(miR)-129-5p下调。此外,102911的过表达抑制了CD3/CD4 T淋巴细胞的增殖并促进细胞凋亡,而敲低102911则产生相反的效果。miR-129-5p参与CD3/CD4 T淋巴细胞的增殖和凋亡,可能是102911的一个有前景的靶点。此外,SOX6是miR-129-5p的下游分子。与年轻患者相比,手术创伤后老年患者的免疫功能和T淋巴细胞数量显著下降,且这种下降在接受LLH治疗肝内胆管结石的老年患者中持续时间更长。发现102911/miR-129-5p/SOX6轴参与T淋巴细胞免疫功能,这为肝内胆管结石老年患者的治疗提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f9/7792479/7409f152084f/etm-21-02-09582-g00.jpg

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