The Role of Oxymatrine in Amelioration of Acute Lung Injury Subjected to Myocardial I/R by Inhibiting Endoplasmic Reticulum Stress in Diabetic Rats.

ABSTRACT: Background: Oxymatrine (OMT) is the primary pharmacological component of Sophora flavescens Aiton., which has been shown to possess potent antifibrotic, antioxidant, and anti-inflammatory activities. The aim of the present study was to clarify the protective mechanism of OMT on acute lung injury (ALI) subjected to myocardial ischemia/reperfusion (I/R).

Methods: A myocardial I/R-induced ALI model was achieved in diabetic rats by occluding the left anterior descending coronary artery for 1?h, followed by reperfusion for 1?h. The levels of inflammatory factors (tumor necrosis factor-?, interleukin- (IL-) 6, and IL-17) in bronchoalveolar lavage fluid were assessed using commercially available kits. The index of myocardial injury, including the detection of cardiac troponin I (cTnI), cardiac troponin T (cTnT), lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB), was also determined using commercially available kits. Hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to identify histological changes. The expression levels of endoplasmic reticulum chaperone BiP (GRP78), DNA damage-inducible transcript 3 protein (CHOP), eukaryotic translation initiation factor 2-alpha kinase 3 (PERK), inositol dependent enzyme 1? (IRE1?), ATF6, caspase-3, -9, and-12, Bcl-2, and Bax were determined by Western blotting. The mRNA expression levels of GRP78 and CHOP were detected by reverse transcription-quantitative PCR.

Results: Myocardial I/R increased the levels of cTnI, cTnT, LDH, and CK-MB in diabetic rats. Damaged and irregularly arranged myocardial cells were also observed, as well as more serious ALI with higher lung injury scores and WET/DRY ratios and lower PaO₂. Moreover, the expression of key proteins of endoplasmic reticulum stress (ERS) was increased by I/R injury, including phosphorylated- (p-) PERK, p-IRE1?, and ATF6, as well as decreased levels of apoptosis. These effects were all significantly reversed by OMT treatment.

Conclusions: OMT protects against ALI subjected to myocardial I/R by inhibiting ERS in diabetic rats.

SUBMITTER: Huang Y 

PROVIDER: S-EPMC7714565 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature