Xuan-Fei-Hua-Zhuo Decoction Against LPS-Induced Acute Lung Injury by Regulating the Permeability and Microtubule Stabilization of Pulmonary Microvascular Endothelial Cells in Mice.

Abstract

Acute lung injury (ALI) is an acute bilateral pulmonary infiltration disease, which may finally cause impairment and even loss of lung function. This study aimed to investigate the therapeutic potential and the mechanism of the Xuanfei Huazhuo decoction (XFHZ) against ALI in mice. The ALI mice stimulated by lipopolysaccharide (LPS) were subjected to the treatment of saline, 0.06, 0.11, and 0.22 mg/kg of XFHZ, and 10 mg/kg of fasudil, respectively, for seven consecutive days. It was found that XFHZ significantly attenuated LPS-induced pathological injury and mitochondrial dysfunction of vascular endothelial cells in the lung and suppressed LPS-mediated lung pulmonary edema (lung wet/dry weight ratio), the elevation of vascular permeability (increased total protein and albumin content in bronchoalveolar lavage fluid) and neutrophil infiltration. Microtubule stabilization, a process that could be regulated by GEF-H1, MYPT-1, Tau, and MAP-4, is critical for maintaining the endothelial cell barrier, of which disruption is a pathological hallmark of ALI. XFHZ reduced the expression of GEF-H1 and MYPT-1 at mRNA and protein levels and decreased Tau and MAP-4 protein expression in LPS-induced ALI. XFHZ also suppressed the increase of monomeric tubulin and the decrease of polymeric tubulin in injured lung induced by LPS. This study demonstrated that XFHZ can improve LPS-induced ALI by promoting microtubule stabilization, providing a theoretical basis for the clinical treatment of patients with ALI induced by different factors, including SARS-CoV-2 infection.