Maimendong Decoction Improves Pulmonary Function in Rats With Idiopathic Pulmonary Fibrosis by Inhibiting Endoplasmic Reticulum Stress in AECIIs.

Lan Zhang,Yanan Nan,Liming Di,Shuangshuang He,Yu Li,Mengmeng Shen,Yadong Li

doi:10.3389/fphar.2020.01262

Abstract

This study was designed to investigate the mechanism by which MMDD improves lung function, and observe the effect of MMDD on endoplasmic reticulum stress(ERS) in alveolar type II epithelial cells (AECIIs) of pulmonary fibrosis rats. pulmonary fibrosis animal model was established by intratracheal injection of BLM at a dose of 6mg/kg body weight. Overall, Thirty male SPF Sprague-Dawley rats were randomly divided into control group, BLM group and BLM+MMDD group. BLM+MMDD group rats were fed 24 g/kg over three weeks for twice a day on the fourteenth day after model establishment. MMDD improves pulmonary function of fibrotic rats and reduces the occurrence of endoplasmic reticulum stress in AECIIs. MMDD could significantly improve the forced vital capacity (FVC) of bleomycin-induced pulmonary fibrosis in rats. MMDD reduced the expression of GRP78 and CHOP in AECIIs, increased the secretion of surfactant protein C (SPC) by AECIIs. Moreover, the apoptosis of the fibrosis zone in the lung tissue was remarkably mitigated by administration of MMDD. The finding of this study revealed that MMDD can improve lung function in rats with pulmonary fibrosis by reducing the occurrence of ERS and cell apoptosis of AECIIs. It may provide a new method for the treatment of pulmonary fibrosis.

Highlights

IPF is a chronic progressive fibrotic interstitial pneumonia
When compared with BLM group, the expression of GRP78 and CHOP could be inhibited in groups that were treated with MMDD by immunohistochemistry testing
Compared with the BLM group, surfactant protein C (SPC) retained in AECIIs of BLM + MMDD group was decreased, and SPC secreted to the alveolar surface was increased

Summary

Introduction

IPF is a chronic progressive fibrotic interstitial pneumonia. The lesions caused by IPF are localized in the lungs and occur in middle-aged and elderly men. IPF is a terminal lung disease with pathological manifestations of alveolar structural and its epithelial damage or collapse, and activation and proliferation of lung fibroblasts, Maimendong Decoction Improves Pulmonary Function and excessive accumulation of extracellular matrix, causing an increased pulmonary interstitial and decreased lung function (Longo et al, 2018). Many studies have shown that endoplasmic reticulum stress (ERS) plays an important role in the development of IPF (Korfei et al, 2008; Hsu et al, 2017). These studies have demonstrated that IPF is more sensitive to ERS. ERS can damage AECIIs, and it is more prone to abnormal AECIIs epithelial repairing and processing, which accelerates the development of pulmonary fibrosis (Korfei et al, 2008)

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