重型肝炎中肝前体细胞的检测及分布

Detection of hepatic progenitor cells in patients with severe hepatitis and their distribution

目的 对重型肝炎中肝前体细胞的某些标志物进行检测以明确其存在并探讨其在不同病理类型肝组织中的分布范围及特点。方法 采用免疫组织化学的方法分别对59例重型肝炎病例肝组织标本表达干细胞因子受体(c-kit)、谷胱甘肽S转移酶π(GST-π)、白细胞分化抗原34(CD_(34))、细胞角蛋白19(CK19)、细胞角蛋白18(CK18)、甲胎蛋白(AFP)的情况进行检测。同时,对58例急慢性普通肝炎病例进行检测作为对照。结果 在重型肝炎中存在肝前体细胞,大部分以管状细胞即非典型胆管增殖(ADP)的形式存在,多位于门静脉汇管区、纤维间隔、汇管区或假小叶周边肝实质及炎症灶的周围,可表达c-kit、GST-π、CK19及CK18,而CD_(34)和AFP为阴性;一部分以小肝细胞样细胞的形式存在,可表达c-kit、GST-π及CK18,而CK19、CD_(34)及AFP为阴性。重型肝炎ADP范围明显大于普通肝炎(x^2=63.63,P<0.05),亚急性重型肝炎和慢性重型肝炎病例ADP范围明显大于急性重型肝炎病例。结论 在病毒性肝炎的再生过程中,不同病理类型的特点也不同。普通型肝炎和慢性肝炎轻度主要是以肝细胞的增殖为主,在慢性肝炎中重度有肝前体细胞的参与,而在重型肝炎中,肝细胞的增殖受到损害或抑制,肝脏主要是通过肝干细胞的活化和增殖进行再生。

Objectives To identify hepatic progenitor cells (HPCs) in patients with severe hepatitis (SH) by detecting their markers and investigate the features of their distribution and location. Methods Liver tissues taken from 59 SH patients were tested for the receptor of stem cell factor (c-kit), π-class glutathione S-transferase (GST- π), cluster of differentiation 34 (CD34), cytokeratin 19 (CK19), cytokeratin 18 (CK18) and alpha fetoprotein (AFP) by immunohis-tochemistry (IHC). Meanwhile, 58 patients with acute or chronic hepatitis were also detected to act as controls. Results Hepatic progenitor cells could be seen in SH patients. Most of them existed as ductular cells that had been called 'atypical ductular proliferation (ADP)' or 'atypical ductular reaction' in previous research. These ductular cells were mainly located at the portal areas, fibro septa, periportal parenchyma and the border of the pseudolobuli and inflammatory foci. Further, c-kit, GST- π , CK19 and CK18, but not CD34 and AFP could be detected in these cells. Another kind of HPC was the small hepatocyte-like cell (SHLC), which could express c-kit, GST- π , and CK18, but not CK19, CD34 and AFP. The semi-quantitative analysis showed that the scope of ADP in SH patients was significantly larger than that in acute and chronic hepatitis patients ( x2= 63.62, P < 0.05), and the scope of ADP in subacute severe hepatitis and chronic severe hepatitis patients was also significantly larger than that in acute severe hepatitis patients. Conclusion In the course of regeneration of viral hepatitis, different types of pathology have different features. In acute and chronic hepatitis (G1-2), the regeneration is mainly owing to the proliferation of mature hepatocytes, and in chronic hepatitis (G3-4), there is the participation of HPCs, although they are limited. In severe hepatitis, however, since the replicative capacity of normal hepatocytes is impaired or prohibited, liver regenerates and restores mainly by the means of hepatic stem cells activation and proliferation. But the hepatic stem cells don't differentiate into their mature functional compartments directly at all. There are several intermediary or transition populations. In human severe hepatitis, they are mainly ductular cells, and parts of them are small hepatocyte-like cells.