Objective To investigate the effect and significance of cyclooxygenase-2( COX-2) inhibitors on the expression of the Acsl gene family in the ileum of rats with nonalcoholic fatty liver disease( NAFLD). Methods A total of 45 Sprague-Dawley rats were randomly divided into normal control group( 15 rats given normal diet),NAFLD model group( 15 rats given high-fat diet),and nimesulide group( 15 rats given high-fat diet and nimesulide). All rats were sacrificed after 12 weeks of feeding,and then blood samples were collected from the inferior vena cava to measure total cholesterol( TC) and triglyceride( TG). HE staining and oil red O staining were performed for the liver to evaluate the degree of hepatic steatosis in each group,and quantitative real-time PCR was used to measure the mRNA expression of the Acsl family genes in the ileum. An 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. Results Compared with the normal control group,the NAFLD model group had significant increases in serum TC and TG and marked hepatic steatosis( all P < 0. 05); compared with the NAFLD model group,the nimesulide group had significant reductions in serum TC and TG and degree of hepatic steatosis( all P < 0. 05). Compared with the normal control group,the NAFLD model group had a significant increase in the expression of COX-2 in the ileum( P < 0. 05),and compared with the NAFLD model group,the nimesulide group had a significant reduction in the expression of COX-2 in the ileum( P <0. 05). Compared with the normal control group,the NAFLD model group had significant increases in the mRNA expression of Acsl3 and Acsl5 in the ileum( both P < 0. 05),and compared with the NAFLD model group,the nimesulide group had significant reductions in the mRNA expression of Acsl3 and Acsl5( both P < 0. 05). Conclusion The COX-2 inhibitor nimesulide can regulate the expression of the Acsl gene family in the ileum of rats with NAFLD,suggesting that COX-2 inhibitors may inhibit the progression of NAFLD through the Acsl gene.
[1] YOUNOSSI ZM. Non-alcoholic fatty liver disease-A global public health perspective[J]. J Hepatol,2019,70(3):531-544.
|
[2] CAO MB,DONG L,LU XL,et al. Expression of cyclooxygenase-2 in nonalcoholic fatty liver disease and its significance[J]. J Fourth Milit Med Univ,2008,29(14):1282-1285.(in Chinese)曹名波,董蕾,鲁晓岚,等.环氧合酶-2在非酒精性脂肪肝病中的表达及意义[J].第四军医大学学报,2008,29(14):1282-1285.
|
[3] CUSI K. Role of insulin resistance and lipotoxicity in non-alcoholic steatohepatitis[J]. Clin Liver Dis,2009,13(4):545-563.
|
[4] FOURET G,GAILLET S,LECOMTE J,et al. 20-Week fol owup of hepatic steatosis installation and liver mitochondrial structure and activity and their interrelation in rats fed a high-fat-highfructose diet[J]. Br J Nutr,2018,119(4):368-380.
|
[5] LIU Z,HUANG Y,ZHANG Y,et al. Drosophila Acyl-Co A synthetase long-chain family member 4 regulates axonal transport of synaptic vesicles and is required for synaptic development and transmission[J]. Neurosci,2011,31(6):2052-2063.
|
[6] KRAWCZYK M,BONFRATE L,PORTINCASA P,et al. Nonalcoholic fatty liver disease[J]. Best Pract Res Clin Gastroenterol,2010,24(5):695-708.
|
[7] VELAGAPUDI VR,HEZAVEH R,REIGSTAD CS,et al. The gut microbiota modulates host energy and lipid metabolism in mice[J]. J Lipid Res,2010,51(5):1101-1112.
|
[8] JING XY,YANG XF. The effect of COX-2 on expression of Acsl family related genes in HSC-T6 cells[D]. Hengyang:The University of South China,2014.(in Chinese)靖新艳,阳学风.COX-2对HSC-T6细胞中Acsl家族相关基因表达的影响[D].衡阳:南华大学,2014.
|
[9] BAFFY G. Potential mechanisms linking gut microbiota and portal hypertension[J]. Liver Int,2019,39(4):598-609.
|
[10] LAU E,CARVALHO D,FREITAS P. Gut microbiota:Association with NAFLD and metabolic disturbances[J]. Biomed Res Int,2015,2015:979515.
|
[11] SUO YH,LIU JC. Research advances in the treatment of nonalcoholic fatty liver disease[J]. J Clin Hepatol,2018,34(10):2232-2236.(in Chinese)索宇鸿,刘近春.非酒精性脂肪性肝病的治疗进展[J].临床肝胆病杂志,2018,34(10):2232-2236.
|
[12] COHEN JC,HORTON JD,HOBBS HH. Human fatty liver disease:Old questions and new insights[J]. Science,2011,332(6037):1519-1523.
|
[13] ISMAIL SA,SH ES,ZIADA DH,et al. Cytokeratin-18 in diagnosis of HCC in patients with liver cirrhosis[J]. Asian Pac J Cancer Prev,2017,18(4):1105-1111.
|
[14] BYRNE CD,TARGHER G. NAFLD:A multisystem disease[J]. J Hepatol,2015,62(1 Suppl):s47-s64.
|
[15] LI WY,YUAN CM. Research advances in integrated traditional Chinese and Western medicine therapy for nonalcoholic fatty liver disease[J]. J Clin Hepatol,2020,36(4):919-923.(in Chinese)李文怡,袁成民.非酒精性脂肪性肝病的中西医治疗[J].临床肝胆病杂志,2020,36(4):919-923.
|
[16] TAKAKI A,KAWAI D,YAMAMOTO K. Multiple hits,including oxidative stress,as pathogenesis and treatment target in non-alcoholic steatohepatitis(NASH)[J]. Int J Mol Sci,2013,14(10):20704-20728.
|
[17] JASIRWAN C,LESMANA C,HASAN I,et al. The role of gut microbiota in non-alcoholic fatty liver disease:Pathways of mechanisms[J]. Biosci Microbiota Food Health,2019,38(3):81-88.
|
[18] VEENA J,MURAGUNDLA A,SIDGIDDI S,et al. Non-alcoholic fatty liver disease:Need for a balanced nutritional source[J]. Br J Nutr,2014,112(11):1858-1872.
|
[19] MOURIES J,BRESCIA P,SILVESTRI A,et al. Microbiotadriven gut vascular barrier disruption is a prerequisite for nonalcoholic steatohepatitis development[J]. J Hepatol,2019,71(6):1216-1228.
|
[20] SCHNEIDER KM,BIEGHS V,HEYMANN F,et al. CX3CR1 is a gatekeeper for intestinal barrier integrity in mice:Limiting steatohepatitis by maintaining intestinal homeostasis[J]. Hepatology,2015,62(5):1405-1416.
|
[21] PETITO-DA-SILVA TI,SOUZA-MELLO V,BARBOSA-DASILVA S. Empaglifozin mitigates NAFLD in high-fat-fed mice by alleviating insulin resistance,lipogenesis and ER stress[J]. Mol Cel Endocrinol,2019,498:110539.
|
[22] HU J,HONG W,YAO KN,et al. Ursodeoxycholic acid ameliorates hepatic lipid metabolism in LO2 cells by regulating the AKT/m TOR/SREBP-1 signaling pathway[J]. World J Gastroenterol,2019,25(12):1492-1501.
|
[23] ZHANG C,Mc FARLANE C,LOKIREDDY S,et al. Inhibition of myostatin protects against diet-induced obesityby enhancing fatty acid oxidation and promoting a brown adipose phenotype in mice[J]. Diabetologia,2012,55(1):183-193.
|
[24] TAI FWD. NSAIDs and the small bowel[J]. Current opinion in gastroenterology,2018,12(2):431-455.
|
[25] TTHˇS,JONECOVZ,C`URGALI K,et al. Quercetin attenuates the ischemia reperfusion induced COX-2 and MPO expression in the small intestine mucosa[J]. Biomed Pharmacother,2017,95:346-354.
|
[26] NEESS D,BEK S,ENGELSBY H,et al. Long-chain acylCo A esters in metabolism and signaling:Role of acyl-Co A binding proteins[J]. Prog Lipid Res,2015,59:1-25.
|
[27] POPPELREUTHER M,RUDOLPH B,DU C,et al. The N-terminal region of acyl-Co A synthetase 3 is essential for both the localization on lipid droplets and the function in fatty acid uptake[J]. J Lipid Res,2012,53(5):888-900.
|
[28] BAUER PV,DUCA FA,WAISE T,et al. Lactobacillus gasseri in the upper small intestine impacts an ACSL3-dependent fatty acid-sensing pathway regulating whole-body glucose homeostasis[J]. Cell Metab,2018,27(3):572-587. e6.
|
[29] REINARTZ A,EHLING J,LEUE A,et al. Lipid-induced upregulation of human acyl-Co A synthetase 5 promotes hepatocellular apoptosis[J]. Biochim Biophys Acta,2010,1801(9):1025-1035.
|
[30] TSUJIMOTO S,KISHINA M,KODA M,et al. Nimesulide,a cyclooxygenase-2 selective inhibitor,suppresses obesityrelated non-alcoholic fatty liver disease and hepatic insulin resistance through the regulation of peroxisome proliferator-activated receptorγ[J]. Int J Mol Med,2016,38(3):721-728.
|