肝硬化肝癌大鼠TGF-β_1和受体的表达及其意义

The Experimental Study of TGF-β_1 and Its Receptors Expression in Rats with Hepatic Cirrhosis and Hepatocellul ar Carcinoma

目的:探讨肝硬化、肝癌和肝切除与血清TGF-β1和细胞膜相关受体表达的关系及其意义。方法:将150只Wistar大鼠随机分成3组:A组30只,行70%肝切除;B组60只,制备肝硬化模型,获得模型鼠40只,行70%肝切除;C组60只,制备肝癌模型,获得模型鼠39只,行70%肝切除。采用ELISA法检测各组动物手术前后血清TGF-β1的表达水平,免疫组织化学方法检测各组动物手术前后肝组织中TGF-β受体的表达情况。结果:3组术后血清TGF-β1浓度均较术前显著提高;3组中,肝癌组术前、术后血清TGF-β1浓度最高,肝硬化组次之,组间比较均有显著差异(P均<0.01)。肝癌大鼠和肝硬化大鼠术后血清TGF-β1浓度升高幅度更为明显(与正常大鼠术后升高幅度相比,P<0.01)。正常组和肝硬化、肝癌组手术前后TGF-β受体表达无明显差异,但肝硬化组表达的TGF-β受体较正常高,而癌组织与癌周组织受体表达强度显著提高,其受体所在部位有明显不同。结论:TGF-β1与受体的相关表达与化学诱导的肝硬化和肝癌的发生有一定关系;肝切除术后残留肝硬化组织再生不完全可能与TGF-β1的高强度表达有关;对于肝癌大鼠、正常肝组织和肿瘤组织细胞膜表面受体表达的位置差异,可能是肿瘤细胞逃避TGF-β1对细胞增殖的抑制作用的重要原因。

Objective:The aim of the current study was to compar e serum TGF-β 1 expres-sion and its cell membrance receptors in different liver histologic status.Methods:150wistar rats were randomly divided into three groups.Gro up A(30normal rats),group B(40rats)with hepatocirrhosis and group C(3 9rats)with hepatocellular carcinoma had70%hepatectomy,respec-tively.ELI SA was employed to determine the concentration of TGF-β 1 in serum4days pre-and post-hepatectomy,and immuno-histochemical detecti on was performed to mensurate the TGF-βreceptor complex in liver tissue at the same time.Results:The concentration of TGF-β 1 in serum in all rats post-hepatectomy was greatly higher than the concentr ation prehepatectomy.TGF-β 1 concentration pre-and post hepatectomy in group C were the highest in all the groups,and that of group B took the second place.The concentration differe nce among the three groups was significantly(P<0.01).By immunohistochem istry,although TGF-βreceptors expressed on the plas-ma membrance of normal liver cells,tumoral hepatocytes no longer displayed membrance labeling but rather diffuse intrracytoplasic staining with perinuclear accumulation.Conclusion:(1)C0-ex-pression of TGF-β1and its receptor comples play a role in the development of hepatic fibrosis and hepatocellular carcinoma in duced by chemical drugs administration;(2)The incomplete hyperplasia of liver tissue with fibrosis postoperative may be related with the high level expression of TGF-β1;(3)The escape of tumoral hepatocytes from control of cell proliferation by TGF-β1,despite its over-exprssion in serum post-hepatectomy,minght be related to TGF-βreceptor complex expressing in the cytoplasm perinuclear.