Stellate Ganglion Blockade repairs Intestinal Mucosal Barrier through suppression of Endoplasmic Reticulum Stress following Hemorrhagic Shock

Abstract

Background: Hemorrhagic shock-induced ischemia and hypoxia elicit endoplasmic reticulum stress (ERS) that leads to cell apoptosis, tissue structural damage and organ dysfunction and failure. Stellate ganglion blockade (SGB) has been demonstrated to improve intestinal barrier dysfunction induced by hemorrhagic shock. The present study sought to investigate whether the beneficial effect of SGB on the intestinal mucosal barrier function is via suppression of ERS. Materials and methods: A conscious rat model of hemorrhagic shock (40 ±2 mmHg for 1 hour, followed by resuscitation) was established. The parameters reflecting intestinal morphology and intestinal mucosal barrier function including wet-dry ratio (W/D), intestinal permeability, D-lactic acid (D-LA) and intestinal fatty acid binding protein (I-FABP) in plasma, and expressions of ATF6α, PERK, and IRE1α in intestinal tissues were then observed. Furthermore, the effects of either SGB or ERS inhibitor, 4-phenylbutyric acid (4-PBA), on these parameters in rats with hemorrhagic shock were assessed. The effect of ERS agonist tunicamycin (TM) on the rats subjected with both SGB and hemorrhagic shock was also determined. Results: Either SGB or administration of ERS inhibitor, 4-PBA, alleviated hemorrhagic shock-induced adverse effects such as intestinal mucosal barrier dysfunction and excessive autophagy, which were characterized by damaged intestinal tissue, enhanced intestinal permeability and D-LA and I-FABP levels in plasma, and increased expressions of ATF6α, PERK, IRE1α in intestinal tissue. In contrast, administration of ERS agonist, TM, suppressed the beneficial effects of SGB on intestinal tissue and function during hemorrhagic shock. Conclusion: The SGB repairs intestinal mucosal barrier through suppression of ERS following hemorrhagic shock.

SGB Postconditioning Improves Intestinal Barrier Function by Inhibiting Autophagy in Conscious Rats Following Hemorrhagic Shock and Resuscitation

“…Since intestinal mucosal barrier dysfunction is closely related to increased intestinal permeability [25] , we also tested the plasma concentration of FD4 and the distribution of FD4 in intestinal mucosa and submucosal tissues, and the results showed that SGB postconditioning signi cantly reduced intestinal mucosal permeability after hemorrhagic shock. These pieces of evidence demonstrated that SGB post-processing relieved intestinal barrier dysfunction after the hemorrhagic shock to a certain extent, which is consistent with the role of SGB pre-treatment [15,16] .…”

“…We rst veri ed the effect and mechanism of SGB post-processing on the intestinal injury following hemorrhagic shock. In combination with previous studies on SGB pre-treatment results [15,16] , SGB pre-treatment or posttreatment effectively reduces the intestinal barrier damage after hemorrhagic shock. Still, neither affects blood pressure during acute bleeding.…”

“…According to the conventional method in our laboratory [15,16] , the left side stellate ganglion was blocked by injecting 0.5% ropivacaine hydrochloride (AstraZeneca AB, Sweden). After the rat spontaneously waked up, the appearance of ptosis is the sign of the success of SGB.…”

“…It also regulates immune response and suppresses acute post-traumatic in ammation [13,14] . Studies have shown that SGB pretreatment signi cantly reduces the intestinal barrier damage after hemorrhagic shock, which is related to the inhibition of endoplasmic reticulum stress [15,16] . However, it is not clear whether SGB post-processing can also reduce intestinal barrier damage after hemorrhagic shock, which is pivotal to expand the clinical application of SGB.…”

Autophagy Is Involved in Stellate Ganglion Block Reversing Posthemorrhagic Shock Mesenteric Lymph-Mediated Vascular Hyporeactivity

“…Also, a lymph sample was used for subsequent animal experiments and cytology experiments. Part II: The rats were randomly divided into seven groups, namely, Sham, Sham+SGB, Shock, Shock + SGB, Shock plus 3-methyladenine (3-MA) intraperitoneal injection (30 mg/kg) (Zhang et al, 2015 ) (Shock + 3-MA), Shock + SGB plus rapamycin (Rapa) intraperitoneal injection (10 mg/kg) (James et al, 2016 ) (Shock + SGB + Rapa), and Shock + SGB plus intravenous infusion of PHSML (1 ml/kg) (Yin et al, 2020 ) (Shock + SGB + PHSML), 6 rats in each group. The experimental procedures are shown in Table 1 .…”