Effect of miR-21-3p on lung injury in rats with traumatic hemorrhagic shock resuscitated with sodium bicarbonate Ringer’s solution

Abstract

Background: Restricted fluid resuscitation is the most important early method for treating traumatic hemorrhagic shock (THS). This study sought to explore whether micro ribonucleic acid (miR)-21-3p affected resuscitated THS rats by regulating the glycocalyx and inflammation. Methods: MiRNAs extracted from the lung tissues were analyzed by miRNA microarray assays. A rat model of THS was induced by hemorrhage from a left femur fracture. The pathological change in the lung tissues and glycocalyx structure was observed by hematoxylin and eosin staining and a transmission electron microscope examination. The miR-21-3p expression in the lung tissues and serum was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The levels of glycocalyx-related factors and inflammation-related factors were determined by enzyme linked immunosorbent assays. The expression of glycocalyx-related proteins, cell junction-related proteins, and the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (Akt)/nuclear factor kappa B (NF-κB) signaling pathway-related proteins was analyzed by Western blot.Results: After RT-qPCR verification, the variation trend of miR-21-3p was in line with expected trends.The mean arterial pressure (MAP) and heart rate (HR) were decreased, and the lung injury and damage to the glycocalyx were all aggravated in the THS rats resuscitated with sodium bicarbonate Ringer's solution (BRS) or sodium lactate Ringer's solution (LRS). The expression of miR-21-3p was decreased in the THS rats resuscitated with BRS and increased in the THS rats resuscitated with LRS, and the upregulation of miR-21-3p further decreased the MAP and HR, and increased the levels of syndecan-1 (SDC-1), heparanase-1 (HPA1), interleukin (IL)-6, IL-1β, and tumor necrosis factor alpha (TNF-α) in the serum of the THS rats resuscitated with BRS. The upregulation of miR-21-3p also increased the expression of SDC-1, HPA1, β-catenin, matrix metallopeptidase (MMP)2, and MMP9, but decreased the expression of E-cadherin (E-cad) and activated the PI3K/Akt/NF-κB signaling pathway in the THS rats resuscitated with BRS and transfected with miR-21-3p compared to that of the THS rats resuscitated with BRS and transfected with miR-negative control (NC).Conclusions: miR-21-3p promoted inflammation and glycocalyx damage by activating the PI3K/Akt/NF-κB signaling pathway, thereby aggravating the lung injury in the THS rats resuscitated with BRS.

Effect of Mir-21-3p on Intestinal Injury in Rats With Traumatic Hemorrhagic Shock Resuscitated With the Sodium Bicarbonate Ringer's Solution

“…Studies have shown that it has good effects on the supplement of circulating blood volume and the correction of metabolic acidosis (3,4). Evidence sug-gests that BRS has more advantages on effectiveness and safety than LRS in treating THS (5,6).…”

“…Our previous microRNA microarray showed that miR-21-3p was aberrantly expressed in THS rats and THS/R rats, and miR-21-3p promoted glycocalyx damage, thereby aggravating the lung injury in the THS rats resuscitated with BRS (6). MiR-21-3p has been reported to increase the intestinal epithelial tight junction permeability and promote intestinal barrier dysfunction (11)(12)(13).…”