Li Ying, Du Hui-Bo, Jiang Li-Na, Wang Chen, Yin Meng, Zhang Li-Min, Zhang Hong, Zhao Zhen-Ao, Liu Zhan-Kuang, Niu Chun-Yu, Zhao Zi-Gang
Institute of Microcirculation, Hebei North University, Zhangjiakou, Hebei, People's Republic of China.
Affiliated First Hospital, Hebei North University, Zhangjiakou, Hebei, People's Republic of China.
Inflammation. 2021 Dec;44(6):2543-2553. doi: 10.1007/s10753-021-01523-x. Epub 2021 Sep 17.
Severe hemorrhagic shock leads to excessive inflammation and immune dysfunction, which results in high mortality related to mesenteric lymph return. A recent study showed that stellate ganglion block (SGB) increased the survival rate in rats suffering hemorrhagic shock. However, whether SGB ameliorates immune dysfunction induced by hemorrhagic shock remains unknown. The aim of the present study was to verify the favorable effects of SGB on the proliferation and function of splenic CD4 + T cells isolated from rats that underwent hemorrhagic shock and to investigate the mechanism related to the SGB interaction with autophagy and posthemorrhagic shock mesenteric lymph (PHSML). Male rats underwent SGB or sham SGB and conscious acute hemorrhage followed by resuscitation and multiple treatments. After 3 h of resuscitation, splenic CD4 + T cells were isolated to measure proliferation and cytokine production following stimulation with ConA in vitro. CD4 + T cells isolated from normal rats were treated with PHSML drained from SBG-treated rats, and proliferation, cytokine production, and autophagy biomarkers were detected. Hemorrhagic shock reduced CD4 + T cell proliferation and production of interleukin (IL)-2, IL-4, and tumor necrosis factor-α-induced protein 8-like 2 (TIPE2). SGB or administration of the autophagy inhibitor 3-methyladenine (3-MA) normalized these indicators. In contrast, administration of rapamycin (RAPA) autophagy agonist or intravenous injection of PHSML inhibited the beneficial effects of SGB on CD4 + T cells from hemorrhagic shocked rats. Furthermore, PHSML incubation decreased proliferation and cytokine production, increased LC3 II/I and Beclin-1 expression, and reduced p-PI3K and p-Akt expression in normal CD4 + T cells. These adverse effects of PHSML were also abolished by 3-MA administration, as well as incubation with PHSML obtained from SGB-treated rats. SGB improves splenic CD4 + T cell function following hemorrhagic shock, which is related to the inhibition of PHSML-mediated autophagy.
严重失血性休克会导致过度炎症反应和免疫功能障碍，这会导致与肠系膜淋巴回流相关的高死亡率。最近一项研究表明，星状神经节阻滞（SGB）可提高失血性休克大鼠的存活率。然而，SGB是否能改善失血性休克诱导的免疫功能障碍仍不清楚。本研究的目的是验证SGB对从经历失血性休克的大鼠分离的脾CD4 + T细胞增殖和功能的有益作用，并研究与SGB与自噬和失血性休克后肠系膜淋巴（PHSML）相互作用相关的机制。雄性大鼠接受SGB或假SGB处理，然后进行清醒急性出血，随后进行复苏和多次治疗。复苏3小时后，分离脾CD4 + T细胞以测量体外经刀豆蛋白A刺激后的增殖和细胞因子产生。用从接受SGB治疗的大鼠引流的PHSML处理从正常大鼠分离的CD4 + T细胞，并检测增殖、细胞因子产生和自噬生物标志物。失血性休克降低了CD4 + T细胞增殖以及白细胞介素（IL）-2、IL-4和肿瘤坏死因子-α诱导蛋白8样2（TIPE2）的产生。SGB或自噬抑制剂3-甲基腺嘌呤（3-MA）给药可使这些指标恢复正常。相反，雷帕霉素（RAPA）自噬激动剂给药或静脉注射PHSML会抑制SGB对失血性休克大鼠CD4 + T细胞的有益作用。此外，PHSML孵育降低了正常CD4 + T细胞的增殖和细胞因子产生，增加了LC3 II/I和Beclin-1表达，并降低了p-PI3K和p-Akt表达。3-MA给药以及与从接受SGB治疗的大鼠获得的PHSML孵育也消除了PHSML的这些不良反应。SGB可改善失血性休克后脾CD4 + T细胞功能，这与抑制PHSML介导 的自噬有关。
