慢病毒介导脯氨酰寡肽酶过表达抑制硫代乙酰胺诱导的大鼠肝纤维化*

doi:10.3969/j.issn.1672-5069.2015.02.015

Abstract

Abstract: Objective To investigate the effects of lentivirus-mediated prolyl oligopeptidase overexpression on thioacetamide （TAA）-induced liver fibrosis in rats. Methods 40 male Sprague-Dawley （SD） rats were randomly divided into four groups. Thioacetamide（TAA,5%） was injected intraperitoneally to induce liver fibrosis in rats. After 1-week TAA/saline treatment,rats were given normal saline（normal control group and TAA model group）,empty virus（TAA plus empty vector group）,or lentivirus containing POP gene（lentivirus-POP）（TAA plus lentivirus-POP group）;Rats were sacrificed 4 weeks after initial TAA/saline treatment; Pathological changes of the liver were examed by HE staining and Masson staining;Hydroxyproline content in liver tissues were detected by chemical colorimetric;Real-time PCR and Western blot were used to determinate POP mRNA expression and POP protein content in liver,respectively. Results Relative level of POP protein in model group was（0.123±0.04）,significantly decreased compared with normal control[（0.189±0.052）,P<0.05];POP protein level in rats received lentivirus-POP was（0.304±0.044）,significantly higher than that of other groups（P<0.01）;the changes in POP mRNA expression was similar with POP protein content. The fibrosis grade in TAA model group and empty virus group were mostly of S2,and the semi-quantitative analysis of the fibrotic tissue by Masson staining were （15.2±1.69） and （15.3±4.62）,respectively,which were significantly higher than those of the normal controls and TAA plus lentivirus-POP group[（1.75土0.63） and（7.75±2.71）,P<0.05];Hydroxyproline content in model group and empty virus group were[（504.47±111.15） μg/g wet liver weight] and[（498.32±90.87） μg/g wet liver weight],respectively, significantly higher than that of the normal controls[（298.20±47.47） μg/g wet liver weight,P<0.05],while hydroxyproline content in TAA plus lentivirus-POP group was[（383.52±43.49） μg/g TAA wet liver weight],significantly lower than those of model group and empty virus group（P<0.05）. Conclusions POP expression decreases in fibrotic liver induced by TAA;POP can be successfully overexpressed in rat liver by lentivirus containing POP genes,attenuates TAA-induced liver fibrosis and decreases hydroxyproline content in the rat liver.

Key words: Liver fibrosis, Prolyl oligopeptidase, Lentivirus, Overexpression, Thioacetamide

Wang Jing, Zhou Da, Ding Yongnian, et al.. Lentivirus-mediated prolyl oligopeptidase overexpression attenuates thioacetamide -induced hepatic fibrosis in rats[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2015, 18(2): 168-172.

References

[1] Wells RG.Liver fibrosis:challenges of the new era.Gastroenterology,2009,136:387-388.
[2] Friedman S L. Evolving challenges in hepatic fibrosis. Nat Rev Gastroenterol Hepatol,2010,7（8）:425-436.
[3] Thompson A J,Patel K. Antifibrotic therapies: will we ever get there. Curr Gastroenterol Rep,2010,12（1）:23-29.
[4] Kim K H,Kim N D,Seong B L. Discovery and development of anti-HBV agents and their resistance. Molecules,2010,15（9）: 5878-5908.
[5] Mason A L,Zhang G. Linking human beta retrovirus infection with primary biliary cirrhosis. Gastroenterol Clin Biol,2010,34（6-7）:359-366.
[6] Schuppan D,Gorrell M D,Klein T,et al. The challenge of developing novel pharmacological therapies for non-alcoholic steatohepatitis. Liver Int,2010,30（6）:795-808.
[7] D'agostino G,Kim J D,Liu Z W,et al. Prolyl endopeptidase-deficient mice have reduced synaptic spine density in the CA1 region of the hippocampus,impaired LTP,and spatial learning and memory. Cereb Cortex,2013,23（8）:2007-2014.
[8] Goossens F,De Meester I,Vanhoof G,et al. Distribution of prolyl oligopeptidase in human peripheral tissues and body fluids. Eur J Clin Chem Clin Biochem,1996,34（1）:17-22.
[9] Chen Y W,Liu B W,Zhang Y J,et al. Preservation of basal AcSDKP attenuates carbon tetrachloride-induced fibrosis in the rat liver. J Hepatol,2010,53（3）:528-536.
[10] Suzuki Y,Katagiri F,Sato F,et al. Significant decrease in plasma N-acetyl-seryl-aspartyl-lysyl-proline level in patients with end stage renal disease after kidney transplantation. Biol Pharm Bull,2014,37（6）:1075-1079.
[11] 中华医学会传染病与寄生虫病学分会、肝病学分会联合修订. 病毒性肝炎防治方案. 中华内科杂志,2001,40（1）:62-688.
[12] 中华肝脏病学会肝纤维化学组.肝纤维化诊断及疗效评估共识.中华肝脏病杂志,2002,10:327-328.
[13] Friedman S L. Liver fibrosis-from bench to bedside. J Hepatol,2003,38 Suppl 1:S38-53.
[14] Thompson AJ,Patel K. Antifibrotic therapies:will we ever get there Curr Gastroenterol Rep,2010,12（1）:23-29.
[15] Schuppan D,Gorrell MD,Klein T,et al. The challenge of developing novel pharmacological therapies for non-alcoholic steatohepatitis. Liver Int,2010,30（6）:795-808.
[16] Miranda-Mendez A,Lugo-Baruqui A,Armendariz-Borunda J. Molecular basis and current treatment for alcoholic liver disease. Int J Environ Res Public Health,2010,7（5）:1872-1888.
[17] Matsubara S,Takahashi T,Kimura A P. Localization and subcellular distribution of prolyl oligopeptidase in the mouse placenta. J Mol Histol,2011,42（3）:251-264.
[18] Matsuda T,Sakaguchi M,Tanaka S,et al. Prolyl oligopeptidase is a glyceraldehyde-3-phosphate dehydrogenase-binding protein that regulates genotoxic stress-induced cell death. Int J Biochem Cell Biol,2013,45（4）:850-857.
[19] Wynn T A,Barron L. Macrophages:master regulators of inflammation and fibrosis. Semin Liver Dis,2010,30（3）:245-257.
[20] Yamakawa N,Shimeno H,Soeda S,et al. Regulation of prolyl oligopeptidase activity in regenerating rat liver. Biochim Biophys Acta,1994,1199（3）:279-284.
[21] Matsubara Y,Ono T,Tsubuki S,et al. Transient up-regulation of a prolyl endopeptidase activity in the microsomal fraction of rat liver during postnatal development. Eur J Biochem,1998,252（1）:178-183.
[22] Agirregoitia N,Casis L,Gil J,et al. Ontogeny of prolyl endopeptidase and pyroglutamyl peptidase I in rat tissues. Regul Pept,2007,139（1-3）:52-58.
[23] Myohanen T T,Venalainen J I,Garcia-Horsman J A, et al. Distribution of prolyl oligopeptidase in the mouse whole-body sections and peripheral tissues. Histochem Cell Biol,2008,130（5）:993-1003.
[24] Yang L,Magness ST,Bataller R,et al. NF-kappaB activation in Kupffer cells after partial hepatectomy. Am J Physiol Gastrointest Liver Physiol,2005,289（3）:G530-538.
[25] Myohanen TT,Venalainen JI,Garcia-Horsman JA,et al. Distribution of prolyl oligopeptidase in the mouse whole-body sections and peripheral tissues. Histochem Cell Biol,2008,130（5）:993-1003.
[26] Rath NC,Kannan L,Liyanage R,et al. Thymosin beta in macrophage. J Endocrinol Reprod,2007,11（2）:55-61.
[27] Barrett AJ,Rawlings ND. Oligopeptidases,and the emergence of the prolyl oligopeptidase family. Biol Chem Hoppe Seyler,1992,373（7）:353-360.

Lentivirus-mediated prolyl oligopeptidase overexpression attenuates thioacetamide -induced hepatic fibrosis in rats

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