Yu-pu Hong

Macrophage migration inhibitory factor antagonist (S,R)3‑(4‑hydroxyphenyl)‑4,5‑dihydro‑5‑isoxazole acetic acid methyl ester attenuates inflammation and lung injury in rats with acute pancreatitis in pregnancy

Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine involved in many acute and chronic inflammatory diseases. However, its role in acute lung injury associated with acute pancreatitis in pregnancy (APIP) has not yet been elucidated. The present study was undertaken to clarify the effect and potential mechanism of MIF antagonist (S,R)3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) in the development of acute lung injury in rats with APIP. Eighteen late-gestation SD rats were randomly assigned to three groups: Sham operation (SO) group, APIP group, and ISO-1 group. All the rats were sacrificed 6 h after modeling. The severity of pancreatitis was evaluated by serum amylase (AMY), lipase (LIPA), tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 and assessing the histopathological score. Lung injury was determined by performing histology and inflammatory cell infiltration investigations. Western blot analysis was used to detect the protein expression of MIF, phosphorylated and total P38 and nuclear factor-κB (NF-κB) protein in lungs. The results showed that MIF was upregulated in the lung of APIP rats. Compared with APIP group, the intervention of ISO-1 alleviated the pathological injury of the pancreas and lungs, decreased serum AMY and LIPA, attenuated serum concentrations of TNF-α, IL-1β, and IL-6, reduced the number of MPO-positive cells in the lung and inhibited the activation of P38MAPK and NF-κB. These results suggest that MIF is activated in lung injury induced by APIP. Furhtermore, the present findings indicate that the MIF antagonist ISO-1 has a protective effect on lung injury and inflammation, which may be associated with deactivating the P38MAPK and NF-κB signaling pathway.

Fetal liver injury ameliorated by migration inhibitory factor inhibition in a rat model of acute pancreatitis in pregnancy

This study was designed to investigate and assess fetal liver injury in a rat model of acute pancreatitis in pregnancy (APIP) as well as its possible mechanisms and potential therapeutic targets.

A preliminary study on fetal lung injury in a rat model of acute pancreatitis in pregnancy

Acute pancreatitis in pregnancy (APIP), which was thought to be rare, is becoming more frequent. In addition, high perinatal mortality among fetuses has been reported. Our research aimed to investigate and assess fetal lung injury in a rat model of APIP and its possible mechanisms. The APIP model was induced by sodium taurocholate in Sprague-Dawley rats during the third trimester. Sham-operated (SO) rats in late gestation were used as controls, and dynamic observation and detection in the SO and acute pancreatitis (AP) groups were performed at 3 time-points. Histological changes in the fetal lungs, as well as the maternal pancreas and placenta were assessed. The levels of serum amylase, lipase, TNF-α and IL-1β were detected in maternal rats, and the expression of surfactant proteins A, B, C and D as well as their mRNA were determined. In this study, fetal lung injury as well as maternal pancreas and placenta injuries occurred in a time-dependent manner. The levels of serum amylase, lipase and TNF-α were markedly increased in maternal rats, and the levels of surfactant proteins A, B, C and D in fetal lungs were significantly decreased in the fetal lungs of the AP group. Ultrastructure injuries and the dysregulated synthesis and secretion of pulmonary surfactant proteins were observed in the AP group. Our research suggests that fetal lung injury is involved in the rat model of APIP and that the dysregulated synthesis and secretion of pulmonary surfactant proteins play a critical role in fetal lung injury during APIP.

4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis

Endoplasmic reticulum (ER) stress is a particular process with an imbalance of homeostasis, which plays an important role in pancreatitis, but little is known about how ER stress is implicated in severe acute pancreatitis (SAP) induced pancreatic beta-cell injury. To investigate the effect of 4-phenylbutyric acid (4-PBA) on the beta-cell injury following SAP and the underlying mechanism, twenty-four Sprague-Dawley rats were randomly divided into sham-operation (SO) group, SAP model group, and 4-PBA treatment group. SAP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. 4-PBA or normal saline was injected intraperitoneally for 3 days in respective group before successful modeling. Results showed that 4-PBA attenuated the following: (1) pancreas and islet pathological injuries, (2) serum TNF-α and IL-1β, (3) serum insulin and glucose, (4) beta-cell ultrastructural changes, (5) ER stress markers (BiP, ORP150, and CHOP), Caspase-3, and insulin expression in islet. These results suggested that 4-PBA mitigates pancreatic beta-cell injury and endocrine disorder in SAP, presumably because of its role in inhibiting excessive endoplasmic reticulum stress. This may serve as a new therapeutic target for reducing pancreatic beta-cell injury and endocrine disorder in SAP upon 4-PBA treatment.

Magnesium isoglycyrrhizinate alleviates liver injury in obese rats with acute necrotizing pancreatitis

OBJECTIVE For patients with acute necrotizing pancreatitis (ANP), a high body mass index (BMI) increases the likelihood of acute hepatic injury (AHI). In the current study, we explored whether magnesium isoglycyrrhizinate (MgIg) could alleviate ANP-induced liver injury in obese rats. METHODS Sprague-Dawley (SD) rats were selected for the present study, and the ANP model was established by retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct. Thirty-six SD rats were randomly assigned to six groups: the normal (N), standard rat chow (SRC) normal (SN), SRC ANP (S-ANP), high-fat diet (HFD) normal (H-N), HFD ANP (H-ANP), and MgIg pretreatment HFD ANP (H-ANPT) groups. The rats in the H-ANPT group were treated with MgIg (30 mg/kg) intragastrically for 7 days before the ANP model was established. The rats were sacrificed 12 h after ANP was established, and the blood and pancreatic and liver tissues were collected. Differences in the physiology, pathology and cellular and molecular responses of the rats in each group were examined. RESULT Analyses of serum amylase lipase, alanine aminotransferase and aspartate aminotransferase indicated that obesity aggravated ANP-induced hepatic injury and that MgIg improved liver function. The superoxide dismutase, malondialdehyde, M1 macrophage, M2 macrophage, neutrophil, NF-κB, IL-1β and caspase-3 levels in liver tissue showed that MgIg attenuated H-ANP-induced hepatic injury by inhibiting oxidative stress and inflammation. CONCLUSION Obesity aggravated ANP-induced liver injury via oxidative stress and inflammatory reactions. MgIg alleviated oxidative stress and decreased the inflammatory reaction, protecting the liver against the AHI induced by ANP in obese rats.

Corrigendum to “4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis”

[This corrects the article DOI: 10.1155/2016/4592346.].

Serum thyroid hormones levels are significantly decreased in pregnant rats with acute pancreatitis

Acute pancreatitis in pregnancy (APIP), which was thought to be a rare but severe disease, with a high perinatal mortality among maternal-fetuses. Our research aimed to study and assess thyroid injury in a rat model of APIP and its possible mechanisms. The APIP model was established by retrograde injection with sodium taurocholate. Sham-operated (SO) and APIP groups were performed at 3 time-points. Histological changes in the maternal thyroid and pancreas were assessed. The activities of serum amylase, lipase and levels of FT3, FT4, MDA, TNF-α and IL-1β were detected in maternal rats, and the expression of MIF, ICAM-1 and CD68 in the maternal thyroids were determined. In this study, maternal thyroid injury as well as pancreas injury occurred in a time-dependent manner. The activities of serum amylase, lipase and levels of MDA, TNF-α and IL-1β were markedly increased in acute pancreatitis rats, the levels of serum FT3 and FT4 were obviously decreased in APIP groups, and the expressions of MIF, ICAM-1 and CD68 were significantly increased in the thyroid of the APIP group. Ultrastructural thyroid injuries were observed in the APIP group. Our research suggests that thyroid injury is involved in the rat experimental model of APIP. The degree of thyroid dysfunction is associated with APIP, which may affect the prognosis of acute pancreatitis.

Inhibition of endoplasmic reticulum stress by 4-phenylbutyric acid prevents vital organ injury in rat acute pancreatitis

This study was conducted to investigate the effect of 4-phenylbutyric acid (4-PBA) on vital organ injury following sodium taurocholate-induced acute pancreatitis (AP) in rats and the pertinent mechanism. The serum biochemical indicators and key inflammatory cytokines, histopathological damage and apoptosis of vital organs in rat AP, were evaluated in the presence or absence of 4-PBA. Moreover, mRNA and protein levels of endoplasmic reticulum stress (ERS) markers were assessed. 4-PBA significantly attenuated the structural and functional damage of vital organs, including serum pancreatic enzymes, hepatic enzymes, creatinine, and urea. The morphological changes and infiltration of neutrophils and macrophages were reduced as well. These effects were accompanied by decreased serum levels of proinflammatory TNF-α and IL-1β. Furthermore, 4-PBA diminished the expression of ERS markers (glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein, protein kinase R-like ER kinase, activated transcription factor 6, and type-1 inositol requiring enzyme) in vital organs of AP rats. 4-PBA also reduced AP-induced apoptosis in lung, liver, and kidney tissues as shown by TUNEL assay. The present study demonstrated that 4-PBA protected pancreas, lung, liver, and kidney from injury in rat AP by regulating ERS and mitigating inflammatory response to restrain cell death and further suggested that 4-PBA may have potential therapeutic implications in the disease. NEW & NOTEWORTHY In this study, we suggest that endoplasmic reticulum stress (ERS) is an important player in the development of acute pancreatitis-induced multiorgan injury, providing additional evidence for the proinflammatory role of ERS. Because 4-phenylbutyric acid has been suggested to inhibit ERS in many pathological conditions, it is possible that this effect can be involved in alleviating inflammatory response and cell death to ameliorate vital organ damage following acute pancreatitis induced by sodium taurocholate in rats.