Pneumonia is a common infectious disease with high morbidity and mortality. It is caused by a variety of pathogenic microorganisms that infect the lung parenchyma. Anti-infective drugs are one of the preferred choices for the treatment of pneumonia. Pachymic acid (PA) is a lanolin triterpene compound from Poria cocos, which has antiemetic, anti-inflammatory, and anticancer properties. Although PA inhibits inflammatory response in a variety of diseases, its role in pneumonia is not clear. In this study, we established that PA improved histopathological changes in the lungs of rats with pneumonia. PA inhibited the expression of inflammatory cytokines in the serum of rats having pneumonia. In addition, PA inhibited the apoptosis of cells from rat lung tissues. Mechanically, PA inhibited inflammation and cell apoptosis via NF-κB and MAPK pathways. Therefore, PA could serve as a promising drug for treating pneumonia.
Objectives-In animal models with constrictive pericarditis (CP), detecting the function of cardiac systole by conventional noninvasive ultrasound is a challenge. We aimed to detect cardiac dysfunction in rat models with CP in the early stage by layered speckle tracking. Methods-We compared a rat CP model (n = 23, injected with a solution of 1-mg/mL lipopolysaccharides [0.5 mL] and a 10% talc suspension [0.5 mL]) with a control group (n = 20, no injection). After 8 weeks, conventional echocardiography and layered speckle tracking were used to assess the left ventricular structures and functions in the groups. Results-The global circumferential strain (CS) and longitudinal strain (LS) were decreased in the CP group (P < .05). The CS of the epicardial and middle layers in the CP group was decreased (P < .05), but the endocardial layer was not statistically different. The LS of the epicardial layer was decreased (P < .05), but the middle and endocardial layers were not statistically different. The global free-wall and septal-wall CS of the CP group was decreased (P < .05), mainly due to the decrease of CS of the epicardial and middle layers. The global free-wall LS of the CP group was decreased (P < .05), mainly due to the decrease of LS of the epicardial and middle layers. There were no significant differences between the groups in global LS of the septal wall. Conclusions-In the early stage of CP, subepicardial myocardial damage precedes that of the subendocardial myocardium, and free-wall damage precedes that of the septal wall.
Background: Myocardial fibrosis (MF) is thought to be associated with constrictive pericarditis (CP). miR-146a has been reported to be related to the survival of myocardial fibroblasts and related signal transduction pathways. The aim of this study was to investigate the expression of miR-146a in CP with MF and the activation of the Toll-like receptor 4 (TLR-4) signaling pathway, to understand the molecular mechanism of MF involvement in CP.Methods: Thirty rats with different disease duration were randomly divided into three groups: an 8-week model group (CP-8W group), a 16-week model group (CP-16W group) model, and a normal control group (N group). After the CP model was established in the rats, the myocardial tissues were collected. The expression of miR-146a, the key factors of TLR-4 signaling pathway, including IL-1 receptor-associated kinase 1 (IRAK1), tumor necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor-κB (NF-κB) and p-NF-κB, and the MF indicator α-SMA in myocardial tissue were detected. After treatment with lipopolysaccharide (LPS), primary cultured rat cardiac fibroblasts (CFs) were transfected with miR-146a. RT-PCR and western blot were used to detect the expression of downstream effectors to further verify the function of miRNA-146a in regulating MF via the TLR-4 signaling pathway.Results: miR-146a was increased in the CP-8W group but not in the CP-16W group. IRAK1 and TRAF6 in the CP-16W group were found to be higher than in the N group and CP-8W group. α-SMA in the model groups was higher than in the N group. Compared with the CP-8W group, α-SMA in the CP-16W model group was further increased. In the experiments using CFs, the expression of IRAK1, TRAF6, p-NF-κB and α-SMA increased in the LPS-treated group compared with the N group. After transfection of CFs with the miR-146a mimics, the expression of IRAK1, TRAF6, p-NF-κB and α-SMA decreased compared with the LPS-treated group. Following transfection of CFs with miR-146a inhibitors, the expression of IRAK1, TRAF6, p-NF-κB and α-SMA increased compared with the LPS-treated group.
Conclusions:The expression of miR-146a demonstrated a dynamic change in the CP model; it was increased at the early time point (CP-8W) and then decreased at the 16W time point. miR-146a suppressed MF by inhibiting the target genes TRAF6 and IRAK1 via the TLR-4 signaling pathway.
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