基础医学与临床2024,Vol.44Issue(9):1249-1255,7.DOI:10.16352/j.issn.1001-6325.2024.09.1249
牛磺熊去氧胆酸减轻重症急性胰腺炎诱导的模型大鼠肝损伤
Tauroursodeoxycholic acid attenuates severe acute pancreatitis-induced liver injury in rat models
摘要
Abstract
Objective To investigate the effect and mechanism of tauroursodeoxycholic acid(TUDCA)on severe acute pancreatitis(SAP)-induced liver injury in rat model.Methods Thirty SD rats were randomly divided into three groups(10 in each):shame operation group(SO group),severe acute pancreatitis group(SAP group)and tauroursodeoxycholic acid group(TUDCA group).The SAP model was established by retrogradely injecting 5%sodi-um taurocholate(STC)solution(1 mL/kg)into pancreaticobiliary duct.The TUDCA group rats were intraperi-toneally injected with TUDCA(400 mg/kg·d-1)for three days continuously fore establishing models and the SAP and SO group rats were intraperitoneally injected with the same volume of saline.Rats were sacrificed 12 hrs after modeling,and then peripheral blood and part of pancreatic and liver tissues were collected.The level of amylase(AMY),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)was detected by automatic bio-chemical analyzer.The expression of interleukin-6(IL-6)was detected by enzyme-linked immunosorbent assay(ELISA).The histo-pathological profile of pancreas and liver was examined by hematoxylin-eosin(HE)staining microscopy and liver apoptosis was observed by in situ terminal deoxynucleotide transferase labeling(TUNEL).The expression level of glucose-regulating protein 78(GRP78),protein kinase R-like endoplasmic reticulum kinase(PERK),C/EBP homologous protein(CHOP),nuclear factor-κB p65(NF-κB p65)and caspase-3 protein was determined by Western blot.Results Compared with SO group,the expression level of AMY,AST,ALT and IL-6 was increased in SAP group(P<0.05);pancreas and liver necrosis and hepatocyte apoptosis were found to be more significant and the level of GRP78,PERK,CHOP,NF-κB p65 and caspase-3 protein increased(P<0.05).Com-pared with SAP group,the expression of AMY,AST,ALT and IL-6 was reduced in TUDCA group and pancreas and liver necrosis and hepatocyte apoptosis were less severe.The level of GRP78,PERK,CHOP,NF-κB p65 and caspase-3 protein significantly decreased(P<0.05).Conclusions TUDCA may have a protective mechanism to al-leviate pancreatitis-induced severe and acute liver injury in rats by reducing the occurrence of endoplasmic reticulum stree(ERS),alleviating the inflammation and apoptosis as well as inhibiting PERK signaling pathway.关键词
牛磺熊去氧胆酸/内质网应激/重症急性胰腺炎Key words
tauroursodeoxycholic acid/endoplasmic reticulum stress/severe acute pancreatitis分类
医药卫生引用本文复制引用
殷强,汪磊,李童浩..牛磺熊去氧胆酸减轻重症急性胰腺炎诱导的模型大鼠肝损伤[J].基础医学与临床,2024,44(9):1249-1255,7.基金项目
孝感市自然科学基金(XGKJ2022010012) (XGKJ2022010012)