利拉鲁肽对高脂喂养肥胖大鼠胰腺中核转录因子κB和蛋白酪氨酸磷酸酶1B的影响
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摘要
目的研究利拉鲁肽对高脂喂养肥胖大鼠胰腺中核转录因子κB(NF-κB)和蛋白酪氨酸磷酸酶1B(PTP-1B)表达的影响。方法用高脂饮食诱导建立大鼠肥胖模型,并随机分组对照组和实验组,每组7只;另取7只正常大鼠作为空白组。实验组予以皮下注射利拉鲁肽注射液0.6 mg·kg~(-1)·d~(-1),对照组和空白组均予以皮下注射同体积0.9%NaCl约2 mL。3组大鼠均干预2周。比较3组大鼠胰腺中NF-κB活性和PTP-1B蛋白表达量。结果干预2周后,实验组、对照组和空白组的NF-κB积分灰度值分别为69.2,150.5和70.4,PTP-1B蛋白表达量分别为(1.53±0.34),(1.79±0.12)和(1.32±0.34),实验组和空白组的上述指标比较,差异均无统计学意义(均P>0.05),对照组的上述指标与实验组、空白组比较,差异均有统计学意义(均P<0.05)。结论利拉鲁肽注射液可阻断高脂饮食对胰腺组织NF-κB的活化作用,同时可降低PTP-1B蛋白的表达。
Objective To observe the impact of liraglutide on expression of nuclear factor-kappa B( NF-κB) and protein tyrosine phosphatase-1 B( PTP-1 B) in pancreas of the obese rats induced by high fat diet.Methods Obese rats model induced by high-fat-diet were randomly divided into control group( n = 7 cases) and test group( n = 7 cases).Another 7 normal rats were assigned to blank group. After modeling,test group received subcutaneous injection of liraglutide 0. 6 mg·kg~(-1)·d~(-1) for 2 weeks. Control and blank groups took 2 mL subcutaneous injection of 0. 9% NaCl. We observed the expression and activity of NF-κB and PTP-1 B in pancreas in three groups. Results After 2 weeks exposure,the activity of NF-κB in test,control and blank groups were 69. 2,150. 5 and 70. 4,the expression of PTP-1 B in test,control and blank groups were( 1. 53 ± 0. 34),( 1. 79 ± 0. 12) and( 1. 32 ± 0. 34). The differences were statistically significant between blank group and test or blank groups( all P < 0. 05),and the differences were not significant between test group and blank group( all P > 0. 05). Conclusion Liraglutide injection can block the activation of NF-κB induced by high fat diet in pancreatic tissue thus reducing the expression of PTP-1 B,whichimplied that liraglutide might has been closely involved in the signal transduction pathway of NF-κB.
Objective To observe the impact of liraglutide on expression of nuclear factor-kappa B( NF-κB) and protein tyrosine phosphatase-1 B( PTP-1 B) in pancreas of the obese rats induced by high fat diet.Methods Obese rats model induced by high-fat-diet were randomly divided into control group( n = 7 cases) and test group( n = 7 cases).Another 7 normal rats were assigned to blank group. After modeling,test group received subcutaneous injection of liraglutide 0. 6 mg·kg~(-1)·d~(-1) for 2 weeks. Control and blank groups took 2 mL subcutaneous injection of 0. 9% NaCl. We observed the expression and activity of NF-κB and PTP-1 B in pancreas in three groups. Results After 2 weeks exposure,the activity of NF-κB in test,control and blank groups were 69. 2,150. 5 and 70. 4,the expression of PTP-1 B in test,control and blank groups were( 1. 53 ± 0. 34),( 1. 79 ± 0. 12) and( 1. 32 ± 0. 34). The differences were statistically significant between blank group and test or blank groups( all P < 0. 05),and the differences were not significant between test group and blank group( all P > 0. 05). Conclusion Liraglutide injection can block the activation of NF-κB induced by high fat diet in pancreatic tissue thus reducing the expression of PTP-1 B,whichimplied that liraglutide might has been closely involved in the signal transduction pathway of NF-κB.
引文
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[7]PANZHINSKIY E,REN J,NAIR S.Protein tyrosine phosphatase 1B and insulin resistance:role of endoplasmic reticulum stress/reactive oxygen species/nuclear factor kappa B axis[J].PLo S One,2013,8(10):77228.
[2]STORLIEN L H,JAMES D E,BURLEIGH K M E T A L,et al.Fat feeding causes widespread in vivo insulin resistance,decrease energy expenditure and obesity in the rat[J].Am J Physiol,1986,251(5 Pt 1):E576-E583.
[3]李晨钟,张素华,舒昌达,等.用高脂饮食复制胰岛素抵抗大鼠模型[J].基础医学及临床,2000,20(3):93-95.
[4]张丽娟,邹大进,顾萍,等.高脂饮食诱导的肥胖大鼠胰腺蛋白酪氨酸磷酸酶1B表达增高[J].中华内分泌代谢杂志,2007,23(5):437-441.
[5]MULLER J M,RUPEC R A,BAEUERLE P A.Study of gene regulation by NF-kappa B and AP-1 in response to reactive oxygen intermediates[J].Methods,1997,11(3):301-312.
[6]HO E,CHEN GM,BRAY T M.Supplementation of N-acetylcysteine inhibits NF-κB activation and protects against alloxaninduced diabetes in CD-1 mice[J].FASEB J,1999,13(13):1845-1854.
[7]PANZHINSKIY E,REN J,NAIR S.Protein tyrosine phosphatase 1B and insulin resistance:role of endoplasmic reticulum stress/reactive oxygen species/nuclear factor kappa B axis[J].PLo S One,2013,8(10):77228.