Objective To investigate the protective effect of 4-phenylbutyric acid (PBA) on liver injury induced by severe acute pancreatitis (SAP) in rats and its possible mechanism. Methods Twenty-four SPF adult male Sprague Dawley rats were randomly divided into three groups: shame operation group (SO group,n=8), SAP group (n=8), and PBA group (n=8). SAP model was induced by retrograde injection of 5% sodium taurocholate (1 mL/kg) in biliopancreatic duct in SAP group and PBA group. PBA solution (50 mg/kg) was administeredvia intraperitoneal injection for 3 days prior to establishing models in PBA group. Rats were injected equivalent saline solution instead of PBA solution in SAP group and SO group. All rats were sacrificed at 12 h after modeling. Blood samples were collected by inferior vena cava puncture, and serum levels of amylase (AMY), alanine aminotransferase (ALT), and aspartate transaminase (AST) were measured using a fully automatic chemistry analyzer. The head of pancreas and right lobe of hepatic tissues were harvested and pathological examination was observed under the light microscope. Expressions of glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP) and Caspase-3 in hepatic tissues were evaluated by immunohistochemistry assay. Results Compared with SO group, the serum levels of AMY, ALT and AST were significantly increased in SAP group (P＜0.05). The serum levels of ALT and AST in PBA group were significantly lower than those in SAP group (P＜0.05). There was no difference of the serum levels of AMY between in PBA group and SAP group (P＞0.05). Compared with SO group, the damages of the pancreas and liver tissues and the expressions of GRP78, CHOP and Caspase-3 in hepatic tissues were significantly increased in SAP group (P＜0.05). And the above indices in PBA group were significantly decreased when compared with SAP group. Conclusions PBA can alleviate severe acute pancreatitis-induced liver injury, and the mechanism may be associated with inhibition of endoplasmic reticulum stress (ERS) and reduction of hepatocyte apoptosis.
Objective To explore the effects of 4-phenylbutyric acid (4-PBA) on idiopathic pulmonary fibrosis (IPF) using a murine model of bleomycin (BLM)-induced pulmonary fibrosis. Methods Pulmonary fibrosis was induced in C57BL/6 mice by intratracheal injection of BLM. A total of 120 mice were randomly allocated into three groups: BLM group, BLM+4-PBA group, and control group. Pathology of lung tissue was analyzed to evaluate the degree of pulmonary fibrosis, and the survival of the mice was noted. The expression levels of the endoplasmic reticulum stress markers, activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP), were analyzed in lung tissues from mice. Results BLM induced significant collagen deposition in the lungs of the mice, which was alleviated by 4-PBA. 4-PBA also dramatically improved the pulmonary function and increased the survival rate in the BLM+4-PBA group compared with that in the BLM group. Both the mRNA and protein expression levels of ATF6 and CHOP were significantly reduced in mouse lung tissue after 2 weeks of 4-PBA treatment. Conclusions 4-PBA treatment could alleviate BLM-induced pulmonary fibrosis in mice via the attenuation of endoplasmic reticulum stress.