脾切除对肝纤维化大鼠肝脏PDGF-B的表达及血清PDGF-BB水平的影响
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摘要
目的:血小板衍生生长因子(PDGF)是促进肝纤维化发展的重要因子之一。本课题研究脾切除对肝纤维化大鼠肝脏PDGF-B的表达和血清PDGF-BB水平的影响,从而探讨脾切除在肝纤维化治疗中的作用。
方法:对大鼠皮下注射CCL_4,建立65例肝纤维化大鼠模型。于建模开始,肝纤维化期,及肝硬化期三组切除大鼠脾脏,并设立同期假手术组作为对照组。第一、二组及其对照组于建模后第10周,第三组及其对照组于建模后12周分别取大鼠肝脏和血液标本。用免疫组化SABC方法测定肝脏PDGF-B的表达,HE染色检测肝纤维化,应用双抗体夹心ELISA方法测定血清PDGF-BB水平。
结果:
(1)PDGF-B阳性物质主要位于阳性细胞的胞浆内,呈棕色颗粒。这些细胞分布在汇管区、纤维间隔、炎症区,少数在肝窦内。各切脾组PDGF-B阳性细胞A值(吸光度值)明显低于其对照组。
(2)各切脾组血清中PDGF-BB含量明显低于其对照组。
(3)根据HE染色,建模开始时切脾再行肝纤维化诱导,肝纤维化进程缓慢;建模第5周切脾后,肝脏病理状态比对照组明显缓解;肝硬化期切脾后,肝脏炎性改变和纤维化程度有一定减轻。
结论:
(1)脾脏切除能降低肝纤维化大鼠肝脏PDGF-B以及血清中PDGF-BB的水平,有助于缓解肝纤维化程度。
(2)肝纤维化进程中越早切除脾脏对肝纤维化的延缓作用越大。
Objectives:PDGF is one of important factors which can promote the development of hepatic fibrosis.To discuss the effects of splenectomy on Hepatic fibrosis,we tried to study the effects of splenenctomy on the expression of PDGF-B in the liver and the serum level of PDGF-BB of the rats with Hepatic fibrosis.
Methods:By hypodermic injection CCL_4,we established 65 rat models with hepatic fibrosis,splenectomy were performed in three groups at different phases:before hypodermic injection CCL_4(A group)、five weeks after hypodermic injection CCL_4(B group)、tenth weeks hypodermic injection CCL_4(C group).The control groups were established at the same time.then took samples of the livers and serum of the rats in different phases.The expressions of PDGF in the liver were detected by immunohistochemistry technique and the degree of hepatic fibrosis were detected by HE staining.The serum levels of PDGF-BB were analyzed by ELISA technique.
Results:
(1)PDGF-B was mainly distributed in the intracytoplasm of positive cells.them lay in portal areas、fiberseptation、inflammation areas,and a little in sinus hepaticus.Absorbance values of PDGF-B in the experimental group were significantly lower then The control groups(p＜0.05).
(2)The serum levels of PDGF-BB of the rats after splenectomy were significantly lower than the control groups.The serum levels of PDGF—BB of the rats among the experiment groups respectively were(pg/ml): 37.856±5.893,199.425±17.089,340.718±116.894;However the numerus of the control groups respectively were(pg/ml):1356.882±273.054,1095.150±100.956,1325.658±301.048(P＜0.05).
(3)We could detected the effects of splenectomy on hepaic fibrosis after HE and Masson's staining:the progression of Hepatic fibrosis in A group is slowly;Hepatic pathologic state relieved significantly in B group; the inflammation and fibrosis is relieved in C group.
Conclusion:
(1)Splenectomy could degrade the levels of PDGF-B and The serum levels of PDGF-BB,which conduce relieve hepatic fibrosis.
(2)The time of splenectomy is earlier,the effect of splenectomy on hepaic fibrosis is better.
方法:对大鼠皮下注射CCL_4,建立65例肝纤维化大鼠模型。于建模开始,肝纤维化期,及肝硬化期三组切除大鼠脾脏,并设立同期假手术组作为对照组。第一、二组及其对照组于建模后第10周,第三组及其对照组于建模后12周分别取大鼠肝脏和血液标本。用免疫组化SABC方法测定肝脏PDGF-B的表达,HE染色检测肝纤维化,应用双抗体夹心ELISA方法测定血清PDGF-BB水平。
结果:
(1)PDGF-B阳性物质主要位于阳性细胞的胞浆内,呈棕色颗粒。这些细胞分布在汇管区、纤维间隔、炎症区,少数在肝窦内。各切脾组PDGF-B阳性细胞A值(吸光度值)明显低于其对照组。
(2)各切脾组血清中PDGF-BB含量明显低于其对照组。
(3)根据HE染色,建模开始时切脾再行肝纤维化诱导,肝纤维化进程缓慢;建模第5周切脾后,肝脏病理状态比对照组明显缓解;肝硬化期切脾后,肝脏炎性改变和纤维化程度有一定减轻。
结论:
(1)脾脏切除能降低肝纤维化大鼠肝脏PDGF-B以及血清中PDGF-BB的水平,有助于缓解肝纤维化程度。
(2)肝纤维化进程中越早切除脾脏对肝纤维化的延缓作用越大。
Objectives:PDGF is one of important factors which can promote the development of hepatic fibrosis.To discuss the effects of splenectomy on Hepatic fibrosis,we tried to study the effects of splenenctomy on the expression of PDGF-B in the liver and the serum level of PDGF-BB of the rats with Hepatic fibrosis.
Methods:By hypodermic injection CCL_4,we established 65 rat models with hepatic fibrosis,splenectomy were performed in three groups at different phases:before hypodermic injection CCL_4(A group)、five weeks after hypodermic injection CCL_4(B group)、tenth weeks hypodermic injection CCL_4(C group).The control groups were established at the same time.then took samples of the livers and serum of the rats in different phases.The expressions of PDGF in the liver were detected by immunohistochemistry technique and the degree of hepatic fibrosis were detected by HE staining.The serum levels of PDGF-BB were analyzed by ELISA technique.
Results:
(1)PDGF-B was mainly distributed in the intracytoplasm of positive cells.them lay in portal areas、fiberseptation、inflammation areas,and a little in sinus hepaticus.Absorbance values of PDGF-B in the experimental group were significantly lower then The control groups(p＜0.05).
(2)The serum levels of PDGF-BB of the rats after splenectomy were significantly lower than the control groups.The serum levels of PDGF—BB of the rats among the experiment groups respectively were(pg/ml): 37.856±5.893,199.425±17.089,340.718±116.894;However the numerus of the control groups respectively were(pg/ml):1356.882±273.054,1095.150±100.956,1325.658±301.048(P＜0.05).
(3)We could detected the effects of splenectomy on hepaic fibrosis after HE and Masson's staining:the progression of Hepatic fibrosis in A group is slowly;Hepatic pathologic state relieved significantly in B group; the inflammation and fibrosis is relieved in C group.
Conclusion:
(1)Splenectomy could degrade the levels of PDGF-B and The serum levels of PDGF-BB,which conduce relieve hepatic fibrosis.
(2)The time of splenectomy is earlier,the effect of splenectomy on hepaic fibrosis is better.
引文
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[2]刘海林,李宜海,王丹艺,等.肝纤维化时ⅳ型胶原酶与金属蛋白酶组织抑制因子-1的表达.上海医学,2000,23(2):73-75
[3]Kim E,Fischer B,Platelet-derived growth factor-receptor-beta in pig and cattle blastocysts.Acta Anat(Basel),1997,159:194-203
[4]Marry F,Gentilini A,Pinzani M,et al.Phosphatidylinositol 3-kinase is required for platelet-derived growth factor'saction on hepatic stellate cell.Gastroenterology.1997,112(4):1297
[5]Amakawa M,Endo Y.The motility of hepatic Ito cells can be acquired by their myofibroblastic transformation[J].Arch Histol Cytol.2002,65(2):169-78
[6]Carloni V,Romanelli RG,Pinzani M,et al.Focal adhesion kinase and phospholipase C gamma involvement in adhesion and migration of human hepatic stellate cells[J].Gastroenterology,1997,112(2):523-31
[7]Lu CH,Chen TX,Zhang ZB,et al.The expression of platelet-derived growth factor(PDGF)receptor-beta and its correlation with extracellular matrix in hepatic tissue in hepatic fibrosis rats.Zhong hua Gan Zang Bing Za Zhi.2004 Nov:12(11):663-5
[8]Seifert RA,Hart CE,Phillips PE,et al.Two different subunits associateto create isoform-specific platelet-derived growthfactor receptors.J Biol Chem,1989,264:8771
[9]KellyJD,HaldemanBA,Grant FJ,et al.Platelet-derivedgrowthfactor (PDGF)stimulates PDGF receptor subunit dimerization and intersubunit trans-phosphorylation.J Biol Chem,1991,266:8987
[10]Breitkopfk,Roeyen C,Sawitza I,et al.Expression patterns of PDGF-A,-B,-C and -D and the PDGF-receptors alpha and beta in activated rat hepatic stellate cell(HSC).Cytokine.2005 Sep 7:31(5):349-57
[11]Ikura Y,Morimoto H,Ogami M,et al.Expression of platelet-derived growth factor and its receptor in livers of patients with chronic liver disease[J].J Gastroenterol.1997,32(4):496-501
[12]Zhang BB,Cai WM,Weng HL,et al.Diagnostic value of platelet-derived growth factor-BB,transforming growth factor-betal,matrix metalloprote-inase-I,and tissue inhibitor of matrix metalloproteinase-I in serum and peripheral blood mononuclear cells for hepatic fibrosis[J].J Gastroenterol,2003,9(Ii):2490-6
[13]Gressner AM.Transdifferentiation of hepatic stellate cell(Ito cell)to myofibroblasts:a key event in hepatic fibrogenesis[J].kidney Int Suppl.1996,54:S39-45
[14]刘萱,贾继东.肝纤维化的基因治疗[J].中华肝脏病杂志,2005,13(6):474-475
[15]黄莛庭.我国门静脉高压症外科治疗的特色.中华肝胆外科志,2002,8:122
[16]夏穗生.我国脾脏外科的发展回顾[J].中国实用外科杂志,2004,24(12):705-707
[17]Miura H,Kondo S,Shimada T,et al.Long-term effects of distal splenorenal shuntwith splenopancreatic and gastric disconnection on hypersplenism due to liver cirrhosis[J].Hepatogastroenterology,1999,46(29):2995-2998
[18]Zhang H,Chen J,Kaiser GM,et al.The value of partial splenic autotransplantation in patients with portal hypertension:a prospective randomized study[J].Arch Surg,2002,137(1):89-93.
[19]姜洪池,乔海泉脾脏外科临床与进展哈尔滨:黑龙江科学技术出版社,1997
[20]夏穗生,曹秀峰,姜洪池现代脾脏外科学第2版南京:江苏科技出版,2000
[21]刘俊,端木浩,丁海.脾切除对肝炎后肝硬化门脉高压症免疫功能的影响.中华医学丛刊,2003,3:13-14
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