肝硬化时左右半肝形态及肝硬化相关因子表达的研究
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摘要
目的:研究乙型肝炎肝硬化病人左右半肝形态及肝硬化病人肝组织标本的HE染色和肝硬化相关因子基质金属蛋白酶-2、碱性成纤维细胞生长因子-2的表达。
方法:对30例乙肝肝硬化致门脉高压征行脾切除术和乙肝肝硬化失代偿行肝移植手术病人行CT检查,手术中标本摄片,留取形态学资料。同时留取此30例病人肝组织标本,进行HE染色,根据0-4期标准判断肝纤维化程度并行免疫组化染色检测MMP2和bFGF2的表达。
结果:1) 30例肝硬化患者形态学改变的比较发现右半肝萎缩较左半肝萎缩明显增多;2) HE染色亦显示右半肝肝硬化较左半肝肝硬化明显增多;3) MMP2在病例组左半肝的表达明显高于对照组左半肝表达,有统计学差异;在病例组右半肝的表达明显高于对照组右半肝表达,有统计学差异;在病例组右半肝的表达明显高于病例组左半肝的表达,有统计学差异;4) bFGF2在病例组左半肝表达与对照组左半肝表达经检验无统计学差异。在病例组右半肝表达明显高于对照组右半肝表达,有统计学差异。在病例组右半肝表达明显高于病例组左半肝表达,有统计学差异。
结论:1)肝硬化时左右半肝纤维化程度存在明显地差异性;2) MMP2的表达对左右半肝纤维化程度存在明显地差异性起重要作用;3) bFGF2的表达对左右半肝纤维化程度存在明显地差异性可能起一定作用;4)肝硬化时左右半肝纤维化程度存在明显地差异性,为我们今后治疗肝硬化合并肝癌,手术切除肝组织大小及部位提供了新的理论依据。
Objective To investigate the morphous of left and right half-liver cirrhosis and the expression of related factor of hepatic cirrhosis matrix metalloproteinase 2 (MMP-2) and basic fibroblast growth factor 2 (bFGF-2).
Methods 30 specimens of patients with cirrhotic portal hypertension caused by infection of hepatitis B virus (HBV) cirrhosis and liver transplantation for decompensation stage of posthepatitic cirrhosis had CT scan, the samples were observed with morphologic examination and HE staining method according to 0-Ⅳstage. Immunohistochemistry was used to examine the expression of MMP2 and bFGF2 in the tissues.
Results In the 30 cases with liver cirrhosis, Comparison of morphological changes, the right lobe of liver had a more significant sign of atrophy compared with the left lobe of liver. HE staining showed the degree of cirrhosis in the right lobe of liver was more than that he left lobe. The expression of MMP2 and bFGF2 in the patients group was more obvious than that in the control group, and there was a significant difference between them.
Conclusion The difference between the degree of left and right half-liver hepatic fibrosis in hepatic cirrhosis was significant. There is a close relationship between MMP2, bFGF2 and left and right half-liver fibrosis in hepatic cirrhosis. This research provides some new theoretical basis for the location and the size of the surgical excision of hepatocarcinoma with cirrhosis.
方法:对30例乙肝肝硬化致门脉高压征行脾切除术和乙肝肝硬化失代偿行肝移植手术病人行CT检查,手术中标本摄片,留取形态学资料。同时留取此30例病人肝组织标本,进行HE染色,根据0-4期标准判断肝纤维化程度并行免疫组化染色检测MMP2和bFGF2的表达。
结果:1) 30例肝硬化患者形态学改变的比较发现右半肝萎缩较左半肝萎缩明显增多;2) HE染色亦显示右半肝肝硬化较左半肝肝硬化明显增多;3) MMP2在病例组左半肝的表达明显高于对照组左半肝表达,有统计学差异;在病例组右半肝的表达明显高于对照组右半肝表达,有统计学差异;在病例组右半肝的表达明显高于病例组左半肝的表达,有统计学差异;4) bFGF2在病例组左半肝表达与对照组左半肝表达经检验无统计学差异。在病例组右半肝表达明显高于对照组右半肝表达,有统计学差异。在病例组右半肝表达明显高于病例组左半肝表达,有统计学差异。
结论:1)肝硬化时左右半肝纤维化程度存在明显地差异性;2) MMP2的表达对左右半肝纤维化程度存在明显地差异性起重要作用;3) bFGF2的表达对左右半肝纤维化程度存在明显地差异性可能起一定作用;4)肝硬化时左右半肝纤维化程度存在明显地差异性,为我们今后治疗肝硬化合并肝癌,手术切除肝组织大小及部位提供了新的理论依据。
Objective To investigate the morphous of left and right half-liver cirrhosis and the expression of related factor of hepatic cirrhosis matrix metalloproteinase 2 (MMP-2) and basic fibroblast growth factor 2 (bFGF-2).
Methods 30 specimens of patients with cirrhotic portal hypertension caused by infection of hepatitis B virus (HBV) cirrhosis and liver transplantation for decompensation stage of posthepatitic cirrhosis had CT scan, the samples were observed with morphologic examination and HE staining method according to 0-Ⅳstage. Immunohistochemistry was used to examine the expression of MMP2 and bFGF2 in the tissues.
Results In the 30 cases with liver cirrhosis, Comparison of morphological changes, the right lobe of liver had a more significant sign of atrophy compared with the left lobe of liver. HE staining showed the degree of cirrhosis in the right lobe of liver was more than that he left lobe. The expression of MMP2 and bFGF2 in the patients group was more obvious than that in the control group, and there was a significant difference between them.
Conclusion The difference between the degree of left and right half-liver hepatic fibrosis in hepatic cirrhosis was significant. There is a close relationship between MMP2, bFGF2 and left and right half-liver fibrosis in hepatic cirrhosis. This research provides some new theoretical basis for the location and the size of the surgical excision of hepatocarcinoma with cirrhosis.
引文
1.李玉林,唐建武.病理学[M].第6版.北京:人民卫生出版社.2004,205-209.
2.Friedman SL.Molecular regulation of hepatic fibrosis,an integrated cellular response to tissue injury.J Biol Chem 2000;275:2247-2250.
3.CLENDEN INN NJ,APPELT K.Matrix metallop roteinase inhibitors in cancer therapy[M].Totowa:Humana Press Inc,2001:1.
4.孔丽.MMPs/TIMPs与肝脏疾病[J].临床肝胆病杂志,2001,17(4):195.
5.曹名波.基质金属蛋白酶及其抑制物与肝纤维化.国外医学消化系疾病分册,2005,25:114-117.
6.Tetsu W,Maki N.Akiko I,et al.J Hepatology,2001;35:465-73.
7.Watanabe T,Niioka M,Ishikawa A,et al.Dynamic change of cells expressing MMP-2 mRNA and MT1-MMP mRNA in the recovery from liver fibrosis in the rat.J Hepatol,2001,35(4):465-473.
8.El-Gindy I,El Rahman AT,El-Alim MA,et al.Diagnostic potential of serum matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-las non-invasive markers of hepatic fibrosis in patients with HCV related chronic liver disease.Egypt J Immunol,2003,10(1):27-35.
9.Burgess,W.H.,and Maciag,T.(1989).The heparin-binding(fibroblast)growth factor family of proteins.Annu Rev Biochem 58,575-606.
10.R Rifkin,D.B.,and Moscatelli,D.(1989).Recent developments in the cell biology of basic fibroblast growth factor.J Cell Biol 109,1-6.
11.Ornitz,D.M.,and Itoh,N.(2001).Fibroblast growth factors.Genome Biol 2,REVIEWS3005.
12.胡永芳,吴勇杰,刘仲奇,等.碱性成纤维细胞生长因子与炎症的关系.国外医学抗生素分册,2000,21:278-282.
13.Okada-Ban M,Thiery JP,Jouanneau J.Fibroblast growth factor-2.Int J Biochem Cell Biol,2000,32:263-267.
14.许会彬,张代民,曹英林.碱性成纤维细胞生长因子及受体与肿瘤的关系.临床军医杂志,2005,26:98-100.
15.周志钢,何清濂,林子豪,等.碱性成纤维细胞生长因子作用血管内皮细胞后c-myc基因mRNA表达的实验研究.中华整形外科杂志,2000,18:299-301.
16.黄月红,王小众,陈运新,等.白细胞介素-10,血小板衍生生长因子-BB 对肝星状细胞表达表皮生长因子和碱性成纤维细胞生长因子的影响.中华肝脏病杂志,2004,12:562-563.
17.张愚,屈文东,黄华,等.bFGF及TGFβ1在实验性肝硬化中的免疫组化研究.胃肠病学和肝病学杂志,2005,14:40-44.
1.CLENDEN INN NJ,APPELT K.Matrix metallop roteinase inhibitors in cancer therapy[M].Totowa:Humana Press Inc,2001:1.
2.孔丽.MMPs/TIMPs与肝脏疾病[J].临床肝胆病杂志,2001,17(4):195.
3.陈华江.基质金属蛋白酶的结构及其调节机制[J].国外医学肿瘤学分册,2001,28:20,29.
4.VAN KEMPEN LC,RHEE JS,DEHNEK,et al.Ep ithelial carcino2 genesis:dynamicinter p lay between neop lastic cell sandtheirmicro en2 vironment[J].Differentiation,2002,70:610.
5.LYNCH CC,MATR ISIAN LM.Matrix metallop roteinases in tumor hostcell communication[J].Differentiation,2002,70:561.
6.COX G,O'bYRNE KJ.Matrix metallop roteinase and cancer[J].Anticancer Res,2001,21(6B):4207.
7.L IZASA T,FUJ ISAWA T,SUZUKIM.Elevated levels of circulating p lasma matrixmetallop roteinase29 in non2small cell lung cancer pa2 tients[J].Clin Cancer Res,1999,5(1):149.
8.SHAL INSKY Dr.BREKKEN J,ZOU H.Marked antiangio genic and antium or efficacy of AG 3340 in chem.Oresistant human non2small cell lung cancer tumours single agent and combination therapy stud2 ies[J].Clin Cancer Res,1999,5(7):1905.
9.Arthur M J,Iredale J P.J R Coll Physicians Lond,1994;28:200-208.
10.李保森,游绍莉,赵志海,等.世界华人消化杂志,2003;11:483-485.
11.Arthur M J.Semin Liver Dis,1990;10:47-49.
12.Okazaki I,Arai M,Wada N,et al.Nippon Rinsho,1993;51:428-434.
13.Murawaki Y,Koda M,Yamada S,et al.JHepatol,1993;18:328-334
14.Watanabe T,Niioka M,Ishikawa A,et al.Dynamic change of cells expressing MMP-2mRNA and MT1-MMP mRNA in the recovery from liver fibrosis in the rat.J Hepatol,2001,35(4):465-473
15.El-Gindy I,El Rahman AT,El-Alim MA,et al.Diagnostic potential of serum matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-las non-invasive markers of hepatic fibrosis in patients with HCV related chronic liver disease.Egypt J Immunol,2003,10(1):27-35.
16.王宪波,刘平,唐志鹏,等.大鼠肝纤维化形成中基质金属蛋白酶2、9活性变化的病理意义.中华肝脏病杂志,2004,12:267-270.
17.Leroy V,Monier F,Bottari S,et al.Circulating matrix metalloproteinases 1,2,9 and their inhibitors TIMP-1 and TIMP-2 as serum markers of liver fibrosis in patients with chronic hepatitisC:comparison with PⅢNP and hyaluronic acid.Am J Gastroenterol,2004,99(2):271-279.
18.Xu GF,Li PT,Wang XY,et al.Dynamic changes in the expression of matrix metalloproteinases and their inhibitors,TIMPs,during hepatic fibrosis induced by alcohol in rats.World J Gastroenterol,2004,10(24):3621-3627.
19.Stetler2Stevenson WG.Hewitt R,Corco2 ran M.Matrix metalloproteinases and tu2 mor invasion:from correlation and causality to clinic.Sem in Cancer Bio,1996,7:1472 154.
20.Ries C,Petrides PE.Cytokine regulation of matrix metaloproteinase activity and its regulatory dysfunction in disease.Biol Chem,1995,376:3452355.
21.Burgess,W.H.,and Maciag,T.(1989).The heparin-binding(fibroblast) growth factor family of proteins.Annu Rev Biochem 58,575-606.
22.R Rifkin,D.B.,and Moscatelli,D.(1989).Recent developments in the cell biology of basic fibroblast growth factor.J Cell Biol 109,1-6.
23.Itoh N.FGFs as multifunctional signaling molecules:diversity of st ructure and function (J).Seikagaku,2001,73(7):525-535.
24.Ornitz,D.M.,and Itoh,N.(2001).Fibroblast growth factors.Genome Biol 2,REVIEWS3005.
25.胡永芳,吴勇杰,刘仲奇,等.碱性成纤维细胞生长因子与炎症的关系.国外医学抗生素分册,2000,21:278-282.
26.Okada-Ban M,Thiery JP,Jouanneau J.Fibroblast growth factor-2.Int J Biochem Cell Biol,2000,32:263-267.
27.许会彬,张代民,曹英林.碱性成纤维细胞生长因子及受体与肿瘤的关系.临床军医杂志,2005,26:98-100.
28.周志钢,何清濂,林子豪,等.碱性成纤维细胞生长因子作用血管内皮细胞后c-myc基因mRNA表达的实验研究.中华整形外科杂志,2000,18:299-301.
29.韩斌,王广田.血管生成因子bFGF与肝细胞癌.河南外科学杂志,2000,6:162-164.
30.严家春,陈文笔,马勇,等.慢性乙型肝炎肝组织中碱性成纤维细胞生长因子及其mRNA 的表达.中华传染病学杂志,2004,22:314-317.
31.熊盛,林剑,姚汝华,等.碱性成纤维细胞生长因子与肝素结合性质的研究进展.中国病理生理杂志,2002,18:214-217.
32.付小兵,杨银辉,孙同柱,等.抑制或拮抗内源性bFGF活性对肠缺血再灌注所致肠、肝、肾功能的影响.中国危重病急救医学,2000,12:465-468.
33.黄月红,王小众,陈运新,等.白细胞介素-10,血小板衍生生长因子-BB 对肝星状细胞表达表皮生长因子和碱性成纤维细胞生长因子的影响.中华肝脏病杂志,2004,12:562-563.
34.张愚,屈文东,黄华,等.bFGF及TGFβ1在实验性肝硬化中的免疫组化研究,胃肠病学和肝病学杂志,2005,14:40-44.
35.陈佳,罗成群.碱性成纤维细胞生长因子(bFGF)与创伤愈合.中国烧伤创疡杂志,2005,17:74-76.
36.修日东,张学广.碱性成纤维细胞生长因子治疗口腔黏膜溃疡的临床观察.河北医药.2003,25:637.
37.Molteni R,Fumagalli F,Magnaghi Vet al.Modulation of fibro2 blast grOwth factor22 by stress and cofticosteroids:from devel2 opmefital evellts to adult brain p lasticity[J].Brain Res Rev,2001,37(1-3):249 - 258.
2.Friedman SL.Molecular regulation of hepatic fibrosis,an integrated cellular response to tissue injury.J Biol Chem 2000;275:2247-2250.
3.CLENDEN INN NJ,APPELT K.Matrix metallop roteinase inhibitors in cancer therapy[M].Totowa:Humana Press Inc,2001:1.
4.孔丽.MMPs/TIMPs与肝脏疾病[J].临床肝胆病杂志,2001,17(4):195.
5.曹名波.基质金属蛋白酶及其抑制物与肝纤维化.国外医学消化系疾病分册,2005,25:114-117.
6.Tetsu W,Maki N.Akiko I,et al.J Hepatology,2001;35:465-73.
7.Watanabe T,Niioka M,Ishikawa A,et al.Dynamic change of cells expressing MMP-2 mRNA and MT1-MMP mRNA in the recovery from liver fibrosis in the rat.J Hepatol,2001,35(4):465-473.
8.El-Gindy I,El Rahman AT,El-Alim MA,et al.Diagnostic potential of serum matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-las non-invasive markers of hepatic fibrosis in patients with HCV related chronic liver disease.Egypt J Immunol,2003,10(1):27-35.
9.Burgess,W.H.,and Maciag,T.(1989).The heparin-binding(fibroblast)growth factor family of proteins.Annu Rev Biochem 58,575-606.
10.R Rifkin,D.B.,and Moscatelli,D.(1989).Recent developments in the cell biology of basic fibroblast growth factor.J Cell Biol 109,1-6.
11.Ornitz,D.M.,and Itoh,N.(2001).Fibroblast growth factors.Genome Biol 2,REVIEWS3005.
12.胡永芳,吴勇杰,刘仲奇,等.碱性成纤维细胞生长因子与炎症的关系.国外医学抗生素分册,2000,21:278-282.
13.Okada-Ban M,Thiery JP,Jouanneau J.Fibroblast growth factor-2.Int J Biochem Cell Biol,2000,32:263-267.
14.许会彬,张代民,曹英林.碱性成纤维细胞生长因子及受体与肿瘤的关系.临床军医杂志,2005,26:98-100.
15.周志钢,何清濂,林子豪,等.碱性成纤维细胞生长因子作用血管内皮细胞后c-myc基因mRNA表达的实验研究.中华整形外科杂志,2000,18:299-301.
16.黄月红,王小众,陈运新,等.白细胞介素-10,血小板衍生生长因子-BB 对肝星状细胞表达表皮生长因子和碱性成纤维细胞生长因子的影响.中华肝脏病杂志,2004,12:562-563.
17.张愚,屈文东,黄华,等.bFGF及TGFβ1在实验性肝硬化中的免疫组化研究.胃肠病学和肝病学杂志,2005,14:40-44.
1.CLENDEN INN NJ,APPELT K.Matrix metallop roteinase inhibitors in cancer therapy[M].Totowa:Humana Press Inc,2001:1.
2.孔丽.MMPs/TIMPs与肝脏疾病[J].临床肝胆病杂志,2001,17(4):195.
3.陈华江.基质金属蛋白酶的结构及其调节机制[J].国外医学肿瘤学分册,2001,28:20,29.
4.VAN KEMPEN LC,RHEE JS,DEHNEK,et al.Ep ithelial carcino2 genesis:dynamicinter p lay between neop lastic cell sandtheirmicro en2 vironment[J].Differentiation,2002,70:610.
5.LYNCH CC,MATR ISIAN LM.Matrix metallop roteinases in tumor hostcell communication[J].Differentiation,2002,70:561.
6.COX G,O'bYRNE KJ.Matrix metallop roteinase and cancer[J].Anticancer Res,2001,21(6B):4207.
7.L IZASA T,FUJ ISAWA T,SUZUKIM.Elevated levels of circulating p lasma matrixmetallop roteinase29 in non2small cell lung cancer pa2 tients[J].Clin Cancer Res,1999,5(1):149.
8.SHAL INSKY Dr.BREKKEN J,ZOU H.Marked antiangio genic and antium or efficacy of AG 3340 in chem.Oresistant human non2small cell lung cancer tumours single agent and combination therapy stud2 ies[J].Clin Cancer Res,1999,5(7):1905.
9.Arthur M J,Iredale J P.J R Coll Physicians Lond,1994;28:200-208.
10.李保森,游绍莉,赵志海,等.世界华人消化杂志,2003;11:483-485.
11.Arthur M J.Semin Liver Dis,1990;10:47-49.
12.Okazaki I,Arai M,Wada N,et al.Nippon Rinsho,1993;51:428-434.
13.Murawaki Y,Koda M,Yamada S,et al.JHepatol,1993;18:328-334
14.Watanabe T,Niioka M,Ishikawa A,et al.Dynamic change of cells expressing MMP-2mRNA and MT1-MMP mRNA in the recovery from liver fibrosis in the rat.J Hepatol,2001,35(4):465-473
15.El-Gindy I,El Rahman AT,El-Alim MA,et al.Diagnostic potential of serum matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-las non-invasive markers of hepatic fibrosis in patients with HCV related chronic liver disease.Egypt J Immunol,2003,10(1):27-35.
16.王宪波,刘平,唐志鹏,等.大鼠肝纤维化形成中基质金属蛋白酶2、9活性变化的病理意义.中华肝脏病杂志,2004,12:267-270.
17.Leroy V,Monier F,Bottari S,et al.Circulating matrix metalloproteinases 1,2,9 and their inhibitors TIMP-1 and TIMP-2 as serum markers of liver fibrosis in patients with chronic hepatitisC:comparison with PⅢNP and hyaluronic acid.Am J Gastroenterol,2004,99(2):271-279.
18.Xu GF,Li PT,Wang XY,et al.Dynamic changes in the expression of matrix metalloproteinases and their inhibitors,TIMPs,during hepatic fibrosis induced by alcohol in rats.World J Gastroenterol,2004,10(24):3621-3627.
19.Stetler2Stevenson WG.Hewitt R,Corco2 ran M.Matrix metalloproteinases and tu2 mor invasion:from correlation and causality to clinic.Sem in Cancer Bio,1996,7:1472 154.
20.Ries C,Petrides PE.Cytokine regulation of matrix metaloproteinase activity and its regulatory dysfunction in disease.Biol Chem,1995,376:3452355.
21.Burgess,W.H.,and Maciag,T.(1989).The heparin-binding(fibroblast) growth factor family of proteins.Annu Rev Biochem 58,575-606.
22.R Rifkin,D.B.,and Moscatelli,D.(1989).Recent developments in the cell biology of basic fibroblast growth factor.J Cell Biol 109,1-6.
23.Itoh N.FGFs as multifunctional signaling molecules:diversity of st ructure and function (J).Seikagaku,2001,73(7):525-535.
24.Ornitz,D.M.,and Itoh,N.(2001).Fibroblast growth factors.Genome Biol 2,REVIEWS3005.
25.胡永芳,吴勇杰,刘仲奇,等.碱性成纤维细胞生长因子与炎症的关系.国外医学抗生素分册,2000,21:278-282.
26.Okada-Ban M,Thiery JP,Jouanneau J.Fibroblast growth factor-2.Int J Biochem Cell Biol,2000,32:263-267.
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