肝硬化组织转化生长因子β_1的分布研究及临床意义

Distribution and Clinical Significance of TGF β_1 in the Liver Tissues of Patients with Cirrhosis

目的研究转化生长因子β1(TGFβ1)、胶原纤维和网状纤维在肝硬化组织中的分布、意义及肝细胞癌变对其分布的影响。方法采用免疫组织化学SP法检测30例肝硬化组织和1例大致正常肝组织TGFβ1的表达情况。用Masson染色显示胶原纤维,GordonSweet染色显示网状纤维。CMIAS-8彩色图像分析系统对阳性目标进行分析处理。结果(1)TGFβ1主要位于肝非实质细胞胞浆内,这些细胞主要分布在汇管区、纤维间隔、炎症区;纤维组织中有少量TGFβ1存在;少数肝细胞胞浆内也表达TGFβ1,总阳性率为20%,肝炎肝硬化组TGFβ1阳性表达率与肝炎肝硬化合并原发性肝细胞癌组比较无显著性差异(P>0.05);(2)肝炎肝硬化组TGFβ1的IOD为395.3±291.3,胶原纤维的AD为(6.3±3.8)%,网状纤维的AD为(5.4±2.3)%。TGFβ1的IOD与胶原纤维的AD呈正相关(r=0.8991,P<0.01),与网状纤维的AD呈正相关(r=0.8317,P<0.01);肝炎肝硬化合并原发性肝细胞癌组TGFβ1的IOD为840.7±449.6,胶原纤维的AD为(12.5±4.9)%,网状纤维的AD为(9.2±3.2)%。TGFβ1的IOD与胶原纤维的AD呈正相关(r=0.8025,P<0.01),与网状纤维的AD无相关(r=0.4314,P>0.05)。肝炎肝硬化组TGFβ1的表达、胶原纤维和网状纤维分布与肝炎肝硬化合并原发性肝细胞癌组比较均有显著性差异(P均<0.01);(3)胶原纤维主要分布在汇管区、纤维隔,炎症区,肝窦旁也可见少量存在;网状纤维主要分布在汇管区、纤维隔、炎症区、肝窦旁、实质细胞周围;原发性肝癌及外周肝硬化组织Gordon-Sweet染色显示:肝癌细胞区网状纤维不显色。结论TGFβ1与肝纤维化肝硬化的发生发展密切相关。在肝炎肝硬化,TGFβ1表达增强,当合并原发性肝细胞癌时,TGFβ1有极强表达;TGFβ1可作为原发性肝细胞癌的血清学辅助诊断,Gordon-Sweet染色可作为原发性肝细胞癌的病理学辅助诊断。

Objective To investigate the distribution and significance of transforming growth factor-β_1 (TGFβ_1) 、collagen fiber and reticular fiber, as well as effect of carcinomatous change on the distribution in patients with cirrhosis.Methods TGFβ_1 was detected in liver tissues of 30 patients with cirrhosis and in 1 normal liver tissue on the whole by immunohistochemistry technique-SP. Collagen fiber was detected by Masson`s staining and reticular fiber was detected by Gordon-Sweet staining.Parameters,integra oculus dehter(IOD)for TGFβ_1、area density(AD %) for collagen fiber and reticular fiber,were measured by CMIASs-8 computer colour image analysis system.Results (1)TGFβ_1 was mainly distributed not only in cytoplasm of hepatic interstitial cells that lay in portal areas、fiber septation、inflammation areas,but also in a few hepatocyte cytoplasm and a little in fibrous tissue.Total positive rate of expression of TGFβ_1 in hepatocyte cytoplasm was 20%.There was not prominent difference(P>0.05)between hepatitis B cirrhosis group and cirrhosis with PHC group for expression of TGFβ_1 in hepatocyte cytoplasm;(2)IOD of TGFβ_1、AD of collagen fiber and reticular fiber were 395.1±291.3、(6.3±3.8)% and (5.4±(2.3))% respectively in hepatitis B cirrhosis group. IOD of TGFβ_1 was postive correlation to AD of collagen fiber(r=0.8991,P<0.01),to AD of reticular fiber(r=0.8317,P<0.01);IOD of TGFβ_1、AD of collagen fiber and reticular fiber were 840.7±449.6、(12.5±4.9)% and (9.2±(3.2))% respectively in cirrhosis with PHC group.IOD of TGFβ_1 was postive correlation to AD of collagen fiber(r=0.8991,P<0.01),not correlation to AD of reticular fiber(r= 0.4314,P>(0.05)).There was prominent difference(P<0.01)between the two groups for expression of TGFβ_1、distribution of collagen fiber and reticular fiber;(3)Collagen fiber mainly lay in portal areas、fiber septation 、inflammation areas,by the side hepatic sinusoid a little. Distribution of reticular fiber was similar to collagen fiber, besides around hepatocyte circumference.Reticular fiber was not been found in hepatic carcinoma cell zona by Gormon-Sweet staining in tissues cirrhosis with PHC.Conclusion Distribution of TGFβ_1 is correlated closely with hepar fibrosis and cirrhosis. Expression of TGFβ_1 is enhanced in hepatitis cirrhosis and is exceedingly enhanced in cirrhosis with PHC.TGFβ_1 can assist diagnosising of PHC serologically.Gordon-Sweet staining can assist diagnosising of PHC pathologically.