Estrogen Alleviates Posthemorrhagic Shock Mesenteric Lymph-Mediated Lung Injury Through Autophagy Inhibition

Abstract

Background: Hemorrhagic shock–induced acute lung injury (ALI) is commonly associated with the posthemorrhagic shock mesenteric lymph (PHSML) return. Whether excessive autophagy is involved in PHSML-mediated ALI remains unclear. The relationship between estrogen treatment and PHSML or autophagy needs to verify. The current study will clarify the role of estrogen in reducing PHSML-mediated ALI through inhibition of autophagy. Methods: First, a hemorrhagic shock model in conscious rats was used to observe the effects of 17β-estradiol (E2) on intestinal blood flow, pulmonary function, intestinal and pulmonary morphology, and expression of autophagy marker proteins. Meanwhile, the effect of PHSML and autophagy agonist during E2 treatment was also investigated. Secondly, rat primary pulmonary microvascular endothelial cells were used to observe the effect of PHSML, PHSML plus E2, and E2-PHSML (PHSML obtained from rats treated by E2) on the cell viability. Results: Hemorrhagic shock induced intestinal and pulmonary tissue damage and increased wet/dry ratio, reduced intestinal blood flow, along with pulmonary dysfunction characterized by increased functional residual capacity and lung resistance and decreased inspiratory capacity and peak expiratory flow. Hemorrhagic shock also enhanced the autophagy levels in intestinal and pulmonary tissue, which was characterized by increased expressions of LC3 II/I and Beclin-1 and decreased expression of p62. E2 treatment significantly attenuated these adverse changes after hemorrhagic shock, which was reversed by PHSML or rapamycin administration. Importantly, PHSML incubation decreased the viability of pulmonary microvascular endothelial cells, while E2 coincubation or E2-treated lymph counteracted the adverse roles of PHSML. Conclusions: The role of estrogen reducing PHSML-mediated ALI is associated with the inhibition of autophagy.

STELLATE GANGLION BLOCK REVERSES PHSML-INDUCED VASCULAR HYPOREACTIVITY THROUGH INHIBITING AUTOPHAGY-MEDIATED PHENOTYPIC TRANSFORMATION OF VSMCs

“…Imaging was performed using an ImageQuant LAS 4000 apparatus (GE Co., Boston, MA). The protein expression level was normalized to the internal reference β-actin using Quantity One software (version 4.6.2; Bio-Rad Co., Hercules, CA) (20).…”

“…Under inhalation anesthesia with 2% isoflurane (Shenzhen Ruiwald Life Technology Co., Ltd., Shenzhen, China) by the inhalation anesthesia machine for small animals (MATRX VMR; Midmark Corporation, Dayton, OH), before the surgical and hemorrhage procedures, either the authentic or sham SGB procedures were performed according to previous reports, with minor alterations (12,(15)(16)(17). After hemorrhagic shock (40 mm Hg for 90 min, followed by resuscitation with shed whole blood and equal Ringer's solution), the PHSML and PHSML-SGB were harvested from rats under anesthetic conditions (18)(19)(20).…”

“…The surgical protocol for establishing a hemorrhagic shock model in conscious rats was performed in accordance with the most recent methodologies developed in our laboratory (20). In this model, the total volume of the hemorrhage was 40% of the effective circulating blood volume (body weight  6.12%) (24), and acute hemorrhage was completed within 10 min.…”

Capsaicin Attenuates LPS-Induced Acute Lung Injury by Inhibiting Inflammation and Autophagy Through Regulation of the TRPV1/AKT Pathway

“…23,24 Studies have shown that inhibiting LPS-induced excessive autophagy in alveolar epithelial cells can mitigate inflammatory injury. 25,26 Moreover, excessive autophagy activation has been implicated in the development of ALI, [27][28][29][30] and the effective inhibition of autophagy is a potential therapeutic approach. Thus, modulating autophagy from inducing death to supporting survival could prove effective in the treatment of LPS-induced ALI.…”

Analysis and Identification of Ferroptosis-Related Gene Signature for Acute Lung Injury

“…Acute lung injury (ALI) is a life-threatening pathological respiratory process caused by infection, trauma, radiation, ischemia reperfusion (IR), and other factors (1)(2)(3). Acute lung injury is characterized by increased permeability of the alveolar-capillary membrane, edema, low pulmonary compliance, high pulmonary dead space, diffuse alveolar injury, and even acute hypoxic respiratory failure (4)(5)(6). The basic pathological changes in ALI are injury to alveolar epithelial cells, pulmonary microvascular endothelial cells (7), and alveolar macrophages (8), and its severe clinical manifestation is acute respiratory distress syndrome (ARDS) (9).…”