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Stellate Ganglion Block Improves the Proliferation and Function of Splenic CD4 + T Cells Through Inhibition of Posthemorrhagic Shock Mesenteric Lymph–Mediated Autophagy

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Abstract—

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.

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The data generated for this study are available on request to the corresponding author.

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Funding

This study was supported by the National Natural Science Foundation of China (No. 81770492).

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Author notes

  1. Ying Li and Hui-Bo Du contributed equally to this work.

Authors and Affiliations

  1. Institute of Microcirculation, Hebei North University, Zhangjiakou, Hebei, People’s Republic of China

    Ying Li, Hui-Bo Du, Li-Na Jiang, Chen Wang, Meng Yin, Li-Min Zhang, Hong Zhang, Zhen-Ao Zhao & Zi-Gang Zhao

  2. Affiliated First Hospital, Hebei North University, Zhangjiakou, Hebei, People’s Republic of China

    Ying Li, Meng Yin & Zhan-Kuang Liu

  3. Hebei Key Laboratory of Critical Disease Mechanism and Intervention, Shijiazhuang and Zhangjiakou, Diamond South Road 11, Zhangjiakou, Hebei, People’s Republic of China

    Hui-Bo Du, Li-Na Jiang, Li-Min Zhang, Zhen-Ao Zhao, Chun-Yu Niu & Zi-Gang Zhao

  4. Basic Medical College, Hebei Medical University, ZhongShan East Road 361, Shijiazhuang, 050017, Hebei, People’s Republic of China

    Chun-Yu Niu

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  1. Ying Li
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Contributions

Y.L., H.D., L.J., C.W., M.Y., L.Z., H.Z., Z.Z., and Z.L. performed majority of the animal experiment and laboratory work; Y.L. acquired and analyzed the data; C.N. and Z.Z. were involved in the conception and design of the study and data interpretation and critically revised the manuscript.

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Correspondence to Chun-Yu Niu or Zi-Gang Zhao.

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All the protocols were approved by the Animal Care Committee of Hebei North University (Zhangjiakou, China).

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Li, Y., Du, HB., Jiang, LN. et al. Stellate Ganglion Block Improves the Proliferation and Function of Splenic CD4 + T Cells Through Inhibition of Posthemorrhagic Shock Mesenteric Lymph–Mediated Autophagy. Inflammation 44, 2543–2553 (2021). https://doi.org/10.1007/s10753-021-01523-x

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