Jiang Z, Liu Y, Savas L, Smith L, Bonkovsky H, Baker S, Banner B
Department of Pathology, University of Massachusetts Medical Center, Worcester 01655, USA.
Virchows Arch. 1997 Sep;431(3):189-94. doi: 10.1007/s004280050087.
To study the early stages of cell death in various types of chronic liver injury, liver biopsies from a total of 26 patients, including 7 with chronic hepatitis C(CHC), 4 with chronic hepatitis B(CHB), 7 with alcoholic liver disease (ALD), 4 with autoimmune or drug hepatitis (AI/DH), and 4 with primary biliary cirrhosis(PBC), were examined by an in situ nucleotidyl transferase assay (ISNTA), which detects DNA fragmentation. Positive nuclei in hepatocytes and sinusoidal lining cells were counted in all parenchymal areas, excluding triads and areas of fibrosis, using a computer with Sigmascan software. The number of positive hepatocytes/mm2 was similar in the biopsies of patients with CHC, CHB, ALD and AI/DH, but significantly lower in PBC. The number of positive sinusoidal lining cells/mm2 was significantly greater in biopsies with CHC compared to CHB, ALD, AI/DH and PBC. Double staining revealed that the ISNTA-positive sinusoidal lining cells were also CD68 positive, indicating that they were Kupffer cells. The frequency of ISNTA positivity did not correlate with serum AST or ALT levels, steatosis, cell swelling or cirrhosis. ISNTA-positive hepatocytes were more frequent than acidophilic bodies in every disease category. We conclude that apoptosis may be a common pathway of cell death in different liver diseases, that the high frequency of DNA fragmentation in Kupffer cells in CHC suggests that during chronic hepatitis C infection activated Kupffer cells may be subject to regulatory control by apoptosis and that ISNTA is more sensitive than acidophilic bodies in assessing the degree of cell injury in the liver.
为研究各类慢性肝损伤中细胞死亡的早期阶段，对总共26例患者的肝活检组织进行了检测，其中包括7例慢性丙型肝炎（CHC）患者、4例慢性乙型肝炎（CHB）患者、7例酒精性肝病（ALD）患者、4例自身免疫性或药物性肝炎（AI/DH）患者以及4例原发性胆汁性肝硬化（PBC）患者。采用原位核苷酸转移酶测定法（ISNTA）检测DNA片段化情况，该方法可检测DNA断裂。使用配备Sigmascan软件的计算机，在所有实质区域（不包括汇管区和纤维化区域）计数肝细胞和窦状隙衬里细胞中的阳性细胞核。CHC、CHB、ALD和AI/DH患者活检组织中每平方毫米阳性肝细胞的数量相似，但PBC患者的该数量明显较低。与CHB、ALD、AI/DH和PBC相比，CHC患者活检组织中每平方毫米阳性窦状隙衬里细胞的数量明显更多。双重染色显示，ISNTA阳性的窦状隙衬里细胞也呈CD68阳性，表明它们是库普弗细胞。ISNTA阳性频率与血清AST或ALT水平、脂肪变性、细胞肿胀或肝硬化无关。在每类疾病中，ISNTA阳性肝细胞比嗜酸性小体更常见。我们得出结论，凋亡可能是不同肝病中细胞死亡的共同途径，CHC中库普弗细胞DNA片段化频率较高表明，在慢性丙型肝炎感染期间，活化的库普弗细胞可能受到凋亡的调控，并且在评估肝脏细胞损伤程度方面，ISNTA比嗜酸性小体更敏感。
