促肝细胞生长素对急性肝功能衰竭大鼠肝组织Ki-67表达的影响
王晓东, 朱碧红,潘陈为, 陈永平,温州医学院附属第一医院感染科 浙江省温州市 325027
通讯作者:陈永平,325027, 浙江省温州市府学巷2号,温州医学院附属第一医院. beerfoam@sina.com
电话:0577-88078232
收稿日期:2005-01-10 接受日期:2005-02-02
摘要
目的:观察促肝细胞生长素(hepatocytegrowth-promoting factors，pHGF)对急性肝功能衰竭大鼠肝组织Ki-67表达的影响，探讨肝细胞再生的规律.
, 百拇医药
方法:SD大鼠随机分为正常对照组、D-氨基半乳糖(D-Galactosamine，D-GalN)组和D-GalN+pHGF组，以D-GalN1.2 g/kg腹腔注射制备大鼠急性肝功能衰竭模型，2h后D-GalN+pHGF组大鼠每24h腹腔注射pHGF2 mg/kg，并分别于第1、3、5、7、9、11、13、15d处死各组大鼠6只.如果该时间点前每组有濒死大鼠则提前处死，使每组各时间点处死大鼠总数为6只.采用S-P免疫组织化学法检测肝组织中Ki-67的表达.
结果:D-GalN组大鼠肝组织Ki-67标记指数(Ki-67labeling index，Ki-67-LI)在模型建立成功后第5d达峰值，以后急剧下降，在第15d时达到正常对照组水平，但D-GalN+pHGF组大鼠Ki-67-LI峰值于第3d出现，比D-GalN组早，持续时间长，且各时间点的Ki-67-LI均明显高于D-GalN组，在第15d时仍未降至正常对照组水平，与之相比，明显升高(P<0.01).D-GalN组及D-GalN+pHGF组肝细胞数量逐渐增多，但除第1d外，D-GalN+pHGF组各时间点肝细胞数量明显高于D-GalN组(P<0.01).
, 百拇医药
结论:急性肝功能衰竭时，残存的肝细胞仍有再生能力，但其再生过程受到抑制.pHGF可以提高急性肝功能衰竭大鼠肝组织Ki-67的表达，从而促进肝细胞的再生，但其再生程度同样受到一定程度的抑制.
王晓东,朱碧红,潘陈为,陈永平.促肝细胞生长素对急性肝功能衰竭大鼠肝组织Ki-67表达的影响.世界华人消化杂志 2005;13(6):784-786
ScholzenT, Gerdes J. The Ki-67 protein from the known and the unknown. J Cell Physiol 2000;182:311-322
2 Wu Y, Luo H,Kannaan N, Wu J. The proteasomecontrols the expression of a proliferation associated nuclear
, 百拇医药
antigen Ki-67. J Cell Biochem 2000;76:596-604
3 MacCallum DE,Hall PA. The location of pKi67 in the outer dense fibrillary compartmentof the nucleolus points to a role
in ribosome biogenesis during the celldivision cycle. J Pathol 2000;190:537-544
4 MacCallum DE,Hall PA. Biochemical characterization of pKi67 with the identification ofa mitotic-specific form
, 百拇医药 associated with hyperphosphorylation andaltered DNA binding. Exp Cell Res 1999;252:186-198
5 MacCallum DE,Hall PA. The biochemical characterization of the DNA binding activity ofpKi67. J Pathol 2000;191:286-298
6 Huuhtanen RL,Blomqvist CP, Wiklund TA, Bohling TO, Virolainen MJ, Tukiainen EJ,Tribukait B, Andersson LC.
Comparison of the Ki-67 score and S-phasefraction as prognostic variables in soft-tissue sarcoma. Br J
, http://www.100md.com
Cancer 1999;79:945-951
7 AlexandrakisMG, Passam FH, Kyriakou DS, Dambaki K, Niniraki M, Stathopoulos E. Ki-67proliferation index:
correlation with prognostic parameters andoutcome in multiple myeloma. Am J Clin Oncol 2004;27:8-13
8 Wolfsberger S,Fischer I, Hoftberger R, Birner P, Slavc I, Dieckmann K, Czech T, Budka H,Hainfellner J.
Ki-67 immunolabeling index is an accuratepredictor of outcome in patients with intracranial ependymoma. AmJ
, 百拇医药
Surg Pathol 2004;28:914-920
9 Korabiowska M,Brinck U, Middel P, Brinkmann U, Berger H, Radzun HJ, Ruschenburg I,Droese M. Proliferative activity
in the progression of pigmented skinlesions, diagnostic and prognostic significance. Anticancer Res 2000;20:1781-1785
10 Wong NA, MayerNJ, Mackell S, Gilmour HM, Harrison DJ. Immunohistochemi-cal assessment ofKi-67 and p53
, 百拇医药
expression assists the diagnosis andgrading of ulcerative colitis-related dysplasia. Histopathology 2000;37:108-114
11 范荣山, 石理兰, 冯国和, 赵桂珍, 刘沛. 实验性暴发性肝衰竭大鼠肝脏NK细胞与肝再生的关系.
中国医科大学学报 2003;32:321-323
12 Nomura K, Miyagawa S, Ayukawa K, Soeda J, Taniguchi S, Kawasaki S. Inhibition of urokinase-type plasminogen
activator delays expression of c-jun, activated transforming growth factor beta 1, and matrix metalloproteinase 2
, 百拇医药
during post-hepatectomy liver regeneration in mice. J Hepatol 2002;36:637-644
13 Nozato E, Shiraishi M, Nishimaki T. Up-regulation of hepatocyte growth factor caused by an over-expression
of transforming growth factor beta, in the rat model of fulminant hepatic failure. J Surg Res 2003;115:226-234
14 Enami Y, Kato H, Murakami M, Fujioka T, Aoki T, Niiya T, Murai N, Ohtsuka K, Kusano M. Anti-transforming
, http://www.100md.com
growth factor-beta1 antibody transiently enhances DNA synthesis during liver regeneration after partial hepatectomy
in rats. J Hepatobiliary Pancreat Surg 2001;8:250-258
15 Polimeno L, Capuano F, Marangi LC, Margiotta M, Lisowsky T, Ierardi E, Francavilla R, Francavilla A. The augmenter
of liver regeneration induces mitochondrial gene expression in rat liver and enhances oxidative phosphorylation capacity
of liver mitochondria. Dig Liver Dis 2000;32:510-517
16 Kaido T, Oe H, Imamura M. Interleukin-6 augments hepatocyte growth factor- induced liver regeneration; involvement
of STAT3 activation. Hepatogastroenterology 2004;51:1667-1 670
编辑 张海宁, 百拇医药( 王晓东, 朱碧红, 潘陈为, 陈永平)
通讯作者:陈永平,325027, 浙江省温州市府学巷2号,温州医学院附属第一医院. beerfoam@sina.com
电话:0577-88078232
收稿日期:2005-01-10 接受日期:2005-02-02
摘要
目的:观察促肝细胞生长素(hepatocytegrowth-promoting factors，pHGF)对急性肝功能衰竭大鼠肝组织Ki-67表达的影响，探讨肝细胞再生的规律.
, 百拇医药
方法:SD大鼠随机分为正常对照组、D-氨基半乳糖(D-Galactosamine，D-GalN)组和D-GalN+pHGF组，以D-GalN1.2 g/kg腹腔注射制备大鼠急性肝功能衰竭模型，2h后D-GalN+pHGF组大鼠每24h腹腔注射pHGF2 mg/kg，并分别于第1、3、5、7、9、11、13、15d处死各组大鼠6只.如果该时间点前每组有濒死大鼠则提前处死，使每组各时间点处死大鼠总数为6只.采用S-P免疫组织化学法检测肝组织中Ki-67的表达.
结果:D-GalN组大鼠肝组织Ki-67标记指数(Ki-67labeling index，Ki-67-LI)在模型建立成功后第5d达峰值，以后急剧下降，在第15d时达到正常对照组水平，但D-GalN+pHGF组大鼠Ki-67-LI峰值于第3d出现，比D-GalN组早，持续时间长，且各时间点的Ki-67-LI均明显高于D-GalN组，在第15d时仍未降至正常对照组水平，与之相比，明显升高(P<0.01).D-GalN组及D-GalN+pHGF组肝细胞数量逐渐增多，但除第1d外，D-GalN+pHGF组各时间点肝细胞数量明显高于D-GalN组(P<0.01).
, 百拇医药
结论:急性肝功能衰竭时，残存的肝细胞仍有再生能力，但其再生过程受到抑制.pHGF可以提高急性肝功能衰竭大鼠肝组织Ki-67的表达，从而促进肝细胞的再生，但其再生程度同样受到一定程度的抑制.
王晓东,朱碧红,潘陈为,陈永平.促肝细胞生长素对急性肝功能衰竭大鼠肝组织Ki-67表达的影响.世界华人消化杂志 2005;13(6):784-786
ScholzenT, Gerdes J. The Ki-67 protein from the known and the unknown. J Cell Physiol 2000;182:311-322
2 Wu Y, Luo H,Kannaan N, Wu J. The proteasomecontrols the expression of a proliferation associated nuclear
, 百拇医药
antigen Ki-67. J Cell Biochem 2000;76:596-604
3 MacCallum DE,Hall PA. The location of pKi67 in the outer dense fibrillary compartmentof the nucleolus points to a role
in ribosome biogenesis during the celldivision cycle. J Pathol 2000;190:537-544
4 MacCallum DE,Hall PA. Biochemical characterization of pKi67 with the identification ofa mitotic-specific form
, 百拇医药 associated with hyperphosphorylation andaltered DNA binding. Exp Cell Res 1999;252:186-198
5 MacCallum DE,Hall PA. The biochemical characterization of the DNA binding activity ofpKi67. J Pathol 2000;191:286-298
6 Huuhtanen RL,Blomqvist CP, Wiklund TA, Bohling TO, Virolainen MJ, Tukiainen EJ,Tribukait B, Andersson LC.
Comparison of the Ki-67 score and S-phasefraction as prognostic variables in soft-tissue sarcoma. Br J
, http://www.100md.com
Cancer 1999;79:945-951
7 AlexandrakisMG, Passam FH, Kyriakou DS, Dambaki K, Niniraki M, Stathopoulos E. Ki-67proliferation index:
correlation with prognostic parameters andoutcome in multiple myeloma. Am J Clin Oncol 2004;27:8-13
8 Wolfsberger S,Fischer I, Hoftberger R, Birner P, Slavc I, Dieckmann K, Czech T, Budka H,Hainfellner J.
Ki-67 immunolabeling index is an accuratepredictor of outcome in patients with intracranial ependymoma. AmJ
, 百拇医药
Surg Pathol 2004;28:914-920
9 Korabiowska M,Brinck U, Middel P, Brinkmann U, Berger H, Radzun HJ, Ruschenburg I,Droese M. Proliferative activity
in the progression of pigmented skinlesions, diagnostic and prognostic significance. Anticancer Res 2000;20:1781-1785
10 Wong NA, MayerNJ, Mackell S, Gilmour HM, Harrison DJ. Immunohistochemi-cal assessment ofKi-67 and p53
, 百拇医药
expression assists the diagnosis andgrading of ulcerative colitis-related dysplasia. Histopathology 2000;37:108-114
11 范荣山, 石理兰, 冯国和, 赵桂珍, 刘沛. 实验性暴发性肝衰竭大鼠肝脏NK细胞与肝再生的关系.
中国医科大学学报 2003;32:321-323
12 Nomura K, Miyagawa S, Ayukawa K, Soeda J, Taniguchi S, Kawasaki S. Inhibition of urokinase-type plasminogen
activator delays expression of c-jun, activated transforming growth factor beta 1, and matrix metalloproteinase 2
, 百拇医药
during post-hepatectomy liver regeneration in mice. J Hepatol 2002;36:637-644
13 Nozato E, Shiraishi M, Nishimaki T. Up-regulation of hepatocyte growth factor caused by an over-expression
of transforming growth factor beta, in the rat model of fulminant hepatic failure. J Surg Res 2003;115:226-234
14 Enami Y, Kato H, Murakami M, Fujioka T, Aoki T, Niiya T, Murai N, Ohtsuka K, Kusano M. Anti-transforming
, http://www.100md.com
growth factor-beta1 antibody transiently enhances DNA synthesis during liver regeneration after partial hepatectomy
in rats. J Hepatobiliary Pancreat Surg 2001;8:250-258
15 Polimeno L, Capuano F, Marangi LC, Margiotta M, Lisowsky T, Ierardi E, Francavilla R, Francavilla A. The augmenter
of liver regeneration induces mitochondrial gene expression in rat liver and enhances oxidative phosphorylation capacity
of liver mitochondria. Dig Liver Dis 2000;32:510-517
16 Kaido T, Oe H, Imamura M. Interleukin-6 augments hepatocyte growth factor- induced liver regeneration; involvement
of STAT3 activation. Hepatogastroenterology 2004;51:1667-1 670
编辑 张海宁, 百拇医药( 王晓东, 朱碧红, 潘陈为, 陈永平)
