lncRNA-uc007gqg. 1在非酒精性脂肪肝中的表达规律
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摘要
目的:通过高脂饮食诱发肝脂肪变研究其与lncRNA-uc007gqg. 1及GRP94、Caspase-3表达水平的相关性。方法:将80只8周龄新西兰雄性大耳白兔随机分为2组,对照组40只给予标准饮食,实验组40只给予高脂高胆固醇饮食喂养制非酒精性脂肪肝(NAFLD)模型。随机各取10只分别在造模第1、4、6、8 w检测两组兔的血生化指标;收集肝脏组织观察病理表现;分别以实时定量PCR和Westernblotting检测肝脏组织lncRNA-uc007gqg. 1和GRP94、Caspase-3蛋白的表达水平。结果:与对照组相比,实验组ALT、AST、TC、LDL、HDL水平在造模4 w时出现明显增高;ALB、TB、CRP水平在造模6 w时明显增高;GGT、TG、ALT与AST比值水平在造模6、8 w时明显升高(P<0.01);肝细胞脂肪样变明显增加;肝组织lncRNA-uc007gqg. 1基因表达水平和GRP94、Caspase-3蛋白表达量逐渐增加(P<0.05)。结论:肝组织lncRNA-uc007gqg. 1表达水平升高与脂肪肝病变密切相关,可能参与NAFLD疾病进展,提示lncRNA-uc007gqg. 1可能是防治该疾病的一个新靶点。
Objective:To investigate the relationship between high-fat diet-induced hepatic steatosis and the expression of GRP94, Caspase-3 and lncRNA-uc007 gqg. 1. Methods: Eighty 8-week-old New Zealand male white rabbits were randomly divided into control group(n=40) and experimental group(n=40). The blood biochemical indexes of 10 rabbits in each group were measured at the 1 st, 4 th, 6 th and 8 th week of the model, respectively. The pathological features of liver tissue were collected and the expression levels of lncRNA-uc007 gqg. 1 and GRP94,Caspase-3 protein in liver tissue were detected by real-time quantitative PCR and Westernblotting, respectively. Results: Compared with the control group, the levels of ALT,AST,TC,LDL,HDL and ALB,TB and CRP in the experimental group were significantly higher than those in the control group at the 4 th weeks and 6 th weeks, respectively. GGT,TG and the ratio of ALT to AST increased significantly at 6 weeks, and increased significantly at 8 weeks(P<0.01). The expression of lncRNA-uc007 gqg. 1 and GRP94,Caspase-3 protein increased gradually in liver tissue(all P<0.05). Conclusion: Uc007 gqg. 1 may be involved in the progression of NAFLD, suggests that uc007 gqg. may be a new target for the prevention and treatment of NAFLD.
Objective:To investigate the relationship between high-fat diet-induced hepatic steatosis and the expression of GRP94, Caspase-3 and lncRNA-uc007 gqg. 1. Methods: Eighty 8-week-old New Zealand male white rabbits were randomly divided into control group(n=40) and experimental group(n=40). The blood biochemical indexes of 10 rabbits in each group were measured at the 1 st, 4 th, 6 th and 8 th week of the model, respectively. The pathological features of liver tissue were collected and the expression levels of lncRNA-uc007 gqg. 1 and GRP94,Caspase-3 protein in liver tissue were detected by real-time quantitative PCR and Westernblotting, respectively. Results: Compared with the control group, the levels of ALT,AST,TC,LDL,HDL and ALB,TB and CRP in the experimental group were significantly higher than those in the control group at the 4 th weeks and 6 th weeks, respectively. GGT,TG and the ratio of ALT to AST increased significantly at 6 weeks, and increased significantly at 8 weeks(P<0.01). The expression of lncRNA-uc007 gqg. 1 and GRP94,Caspase-3 protein increased gradually in liver tissue(all P<0.05). Conclusion: Uc007 gqg. 1 may be involved in the progression of NAFLD, suggests that uc007 gqg. may be a new target for the prevention and treatment of NAFLD.
引文
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[2] YOUNOSSI Z M,STEPANOVA M,RAFIQ N,et al.Nonalcoholic steatofibrosis independently predicts mortality in nonalcoholic fatty liver disease[J].Hepatol Commun,2017,1(5):421- 428.
[3] RUFINATSCHA K,RESS C,FOLIE S,et al.Metabolic effects of reduced growth hormone action in fatty liver disease[J].Hepatol Int,2018,12(5):474- 481.
[4] ZHU X P,XIAO Z H,XU Y M,et al.Differential impacts of soybean and fish oils on hepatocyte lipid droplet accumulation and endoplasmic reticulum stress in primary rabbit hepatocytes[J].Gastroenterol Res Pract,2016,2016(6):9717014.
[5] YOUNOSSI Z M,BLISSETT D,BLISSETT R,et al.The economic and clinical burden of nonalcoholic fatty liver disease in the united states and europe[J].Hepatology,2016,64(5):1577- 1586.
[6] LEBEAUPIN C,VALLéE D,HAZARI Y,et al. Endoplasmic reticulum stress signalling and the pathogenesis of non- alcoholic fatty liver disease[J].J Hepatol,2018,69(4):927- 947.
[7] CHEN T,ZHU H,WANG Y,et al.Apoptosis of bone marrow mesenchymal stromal/stem cells via the mapk and endoplasmic reticulum stress signaling pathways[J].Am J Transl Res,2018,10(8):2555- 2566.
[8] ALBHAISI S,ISSA D,ALKHOURI N,et al.Non- alcoholic fatty liver disease:a pandemic disease with multisystem burden.Hepatobiliary Surg Nutr,2018,7(5):389- 391.
[9] JOO I,LEE J M,YOON J H,et al.Nonalcoholic fatty liver disease:intravoxel incoherent motion diffusion- weighted mr imaging- an experimental study in a rabbit model[J].Radiology,2014,270(1):131- 40.
[10] 中华医学会肝脏病学分会脂肪肝和酒精性肝病学组.非酒精性脂肪性肝病诊断标准[J].中华肝脏病杂志,2003,11(2):71.
[11] RAO R V,NIAZI K,MOLLAHAN P,et al.Coupling endoplasmic reticulum stress to the cell- death program:a novel hsp90- independent role for the small chaperone protein p23[J].Cell Death Differ,2007,14(6):1172- 1180.
[12] KOBAYASHI M,SUZUKI M,OHNO T,et al.Detection of differentially expressed candidate genes for a fatty liver qtl on mouse chromosome 12[J].BMC Genet,2016,17(1):1- 10.
[13] WANG C Y,JéGU T,CHU H P,et al.Smchd1 merges chromosome compartments and assists formation of super- structures on the inactive x[J].Cell,2018,174(2):406- 421.
[14] PARAFATI M,KIRBY R J,KHORASANIZADEH S,et al.A nonalcoholic fatty liver disease model in human induced pluripotent stem cell- derived hepatocytes,created by endoplasmic reticulum stress- induced steatosis[J].Dis Model Mech,2018,11(9):dmm033530.
[15] PARAFATI M,RHO H S,KIM A,et al.Fxr inhibits endoplasmic reticulum stress- induced nlrp3 inflammasome in hepatocytes and ameliorates liver injury[J].Cell Rep,2018,24(11):2985- 2999.
[16] WANG D,LAO L,PANG X,et al.Asiatic acid from potentilla chinensis alleviates non- alcoholic fatty liver by regulating endoplasmic reticulum stress and lipid metabolism[J].Int Immunopharmacol,2018,65:256- 267.
[17] LIU C,FU Q,MU R,et al.Dexmedetomidine alleviates cerebral ischemia- reperfusion injury by inhibiting endoplasmic reticulum stress dependent apoptosis through the perk- chop- caspase- 11 pathway[J].Brain Res,2018,1701:246- 254.