Celecoxib attenuates hepatocyte apoptosis by inhibiting endoplasmic reticulum stress in thioacetamide-induced cirrhotic rats  

作　　者：Wei Su Yang Tai Shi-Hang Tang Yan-Ting Ye Chong Zhao Jin-Hang Gao Bi-Guang Tuo Cheng-Wei Tang 

机构地区：[1]Department of Gastroenterology,West China Hospital,Sichuan University,Chengdu 610041,Sichuan Province,China [2]Department of Gastroenterology,Affiliated Hospital,Zunyi Medical University,Zunyi 563003,Guizhou Province,China [3]Laboratory of Gastroenterology and Hepatology,West China Hospital,Sichuan University,Chengdu 610041,Sichuan Province,China

出　　处：《World Journal of Gastroenterology》2020年第28期4094-4107,共14页世界胃肠病学杂志（英文版）

基　　金：the National Natural Science Fund of China,No.U1702281,No.81670551,and No.81873584.

摘　　要：BACKGROUND Endoplasmic reticulum(ER)stress is an important mechanism in the progression of chronic and acute liver diseases,especially in the progression and recovery of liver fibrosis.Excessive and long-term ER stress induces apoptosis.ER stressinduced apoptosis is considered to be an important pathway in the development of liver fibrosis.Cyclooxygenase-2(COX-2)induction is also closely related to ER stress.In our previous studies,we showed that celecoxib,a COX-2 inhibitor,improves liver fibrosis and portal hypertension.However,the role and mechanism of celecoxib in alleviating liver fibrosis remain unclear.AIM To investigate whether celecoxib alleviates liver fibrosis by inhibiting hepatocyte apoptosis via the ER stress response.METHODS Cirrhosis was induced by intraperitoneal injections of thioacetamide(TAA)for 16 wk(injection dose is 200 mg/kg per 3 d for the first 8 wk and 100 mg/kg per 3 d after 8 wk).Thirty-six male Sprague-Dawley rats were randomly divided into three groups,namely,control group,TAA group,and TAA+celecoxib group.In the last 8 wk,TAA-induced cirrhotic rats received celecoxib(20 mg/kg/day)or the vehicle by gastric gavage.After 16 wk,the rats were sacrificed,and serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and albumin(ALB)were detected.The hepatic fibrosis areas were evaluated by Sirius red staining and the degree of fibrosis was assessed by measuring the level of hydroxyproline.ER stress levels were evaluated by detecting the marker proteins glucose-regulated protein 78(GRP78),CCAAT/enhancer binding protein homologous protein(CHOP),PKR-like ER protein kinase(PERK),activating transcription factor 6(ATF6),and inositol-requiring enzyme 1 alpha(IRE1α).Apoptosis levels were evaluated by detecting caspase-12 and caspase-3.RESULTS The serum ALT and AST levels in the liver were significantly reduced by celecoxib;however,the serum ALB had no significant changes.Celecoxib significantly reduced the degree of liver fibrosis and the levels of hydroxyproline(-38%and-25.7%,respectiv

关 键 词：Liver fibrosis Endoplasmic reticulum stress CELECOXIB CYCLOOXYGENASE-2 CCAAT/enhancer binding protein homologous protein Apoptosis 

分 类 号：R575.2[医药卫生—消化系统]