Protective effect of urolithin A pretreatment in a rat model of hepatic ischemia-reperfusion injury

• Main Author: MI Kai
• Format: Article
• Language: zho
• Published: Editorial Department of Journal of Clinical Hepatology 2020-08-01
• Series: Linchuang Gandanbing Zazhi
• Online Access: http://www.lcgdbzz.org/qk_content.asp?id=10964
• ISSN: 1001-5256; 1001-5256

ObjectiveTo investigate the protective effect of urolithin A (Uro-A) against hepatic ischemia-reperfusion injury (HIRI) in rats. MethodsA total of 40 Sprague-Dawley rats were randomly divided into sham-operation group, model group, low-dose Uro-A (1 mg/kg) group, and high-dose Uro-A (3 mg/kg) group, with 10 rats in each group. Before modeling, the rats in the low- and high-dose Uro-A groups were given the drug by gavage once a day for 5 consecutive days. The model was established after anesthesia, and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were measured at 6 hours after the recovery of blood flow. ELISA was used to measure the content of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the liver, and liver pathological injury and hepatocyte apoptosis were evaluated. Western blot was used to measure the expression of the endoplasmic reticulum chaperone glucose-regulated protein 78 (GRP78), the downstream transcription factor CHOP, and the apoptosis protein caspase-12 in the liver. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group, the high-dose Uro-A group had significantly lower levels of ALT, AST, LDH, MDA, CAT, IL-1β, IL-6, TNF-α, CHOP, GRP78, and caspase-12 and apoptosis rate and a significantly higher content of SOD (all P＜0.05). The model group had severe damage of liver structure, with a positive rate of 90%, while the high-dose Uro-A group had intact liver structure without obvious tissue proliferation or inflammatory cell proliferation, with a negative rate of 80%. Compared with the high-dose Uro-A group, the low-dose Uro-A group had significant increases in the levels of ALT, AST, and LDH and apoptosis rate (all P＜0.05). ConclusionUro-A pretreatment can alleviate liver ischemia-reperfusion injury in rats and reduce oxidative damage and the release of inflammatory factors, possibly by inhibiting the endoplasmic reticulum stress pathways and reducing hepatocyte apoptosis.