背景:非酒精性脂肪性肝炎(NASH)的特征是脂肪沉积,炎症,和肝细胞损伤。NASH的诊断经病理证实。肝细胞气球样是明确诊断的重要发现。最近,在帕金森病中报道了α-突触核蛋白在多个器官中的沉积。因为据报道α-突触核蛋白通过连接蛋白32被肝细胞摄取,所以在NASH中α-突触核蛋白在肝脏中的表达是令人感兴趣的。研究了α-突触核蛋白在NASH肝脏中的积累。p62,泛素的免疫染色,并进行了α-突触核蛋白,并检查了免疫染色在病理诊断中的有用性。
方法:评估20例患者的肝活检组织标本。几种抗α-突触核蛋白的抗体,以及抗连接蛋白32,p62和泛素的抗体用于免疫组织化学分析.染色结果由几位具有不同经验的病理学家评估,并比较了气胀的诊断准确性。
结果:多克隆α-突触核蛋白抗体,不是单克隆抗体,与气球细胞中的嗜酸性粒细胞聚集体反应。还证明了在变性细胞中连接蛋白32的表达。抗p62和泛素的抗体也与一些膨胀细胞反应。在病理学家的评估中,使用苏木精和曙红(H&E)染色的载玻片获得了最高的观察者间一致性,然后对p62和α-突触核蛋白进行免疫染色,H&E染色和免疫染色结果不同。结论:这些结果表明变性α-突触核蛋白掺入气球样细胞,提示α-突触核蛋白参与NASH的发病机制。包括多克隆α-突触核蛋白的免疫染色的组合可能有助于改善NASH的诊断。
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is characterized by fat deposition, inflammation, and hepatocellular damage. The diagnosis of NASH is confirmed pathologically, and hepatocyte ballooning is an important finding for definite diagnosis. Recently, α-synuclein deposition in multiple organs was reported in Parkinson\'s disease. Since it was reported that α-synuclein is taken up by hepatocytes via connexin 32, the expression of α-synuclein in the liver in NASH is of interest. The accumulation of α-synuclein in the liver in NASH was investigated. Immunostaining for p62, ubiquitin, and α-synuclein was performed, and the usefulness of immunostaining in pathological diagnosis was examined.
METHODS: Liver biopsy tissue specimens from 20 patients were evaluated. Several antibodies against α-synuclein, as well as antibodies against connexin 32, p62, and ubiquitin were used for immunohistochemical analyses. Staining results were evaluated by several pathologists with varying experience, and the diagnostic accuracy of ballooning was compared.
RESULTS: Polyclonal α-synuclein antibody, not the monoclonal antibody, reacted with eosinophilic aggregates in ballooning cells. Expression of connexin 32 in degenerating cells was also demonstrated. Antibodies against p62 and ubiquitin also reacted with some of the ballooning cells. In the pathologists\' evaluations, the highest interobserver agreement was obtained with hematoxylin and eosin (H&E)-stained slides, followed by slides immunostained for p62 and α-synuclein, and there were cases with different results between H&E staining and immunostaining CONCLUSION: These results indicate the incorporation of degenerated α-synuclein into ballooning cells, suggesting the involvement of α-synuclein in the pathogenesis of NASH. The combination of immunostaining including polyclonal α-synuclein may contribute to improving the diagnosis of NASH.