库普弗细胞对原代培养贮脂细胞激活的调节作用

目的：观察库普弗细胞在贮脂细胞激活中的促进转化、促增殖及促进细胞外基质合成的效应；方法：采用库弗细胞和贮脂细胞分离培养，流式细胞仪测定ＤＮＡ含量，免疫组化和图像分析对贮脂细胞中Ⅰ、Ⅲ、Ⅳ型胶原和纤维粘连蛋白进行定量分析，液闪法检测贮脂细胞中＾３Ｈ－脯氨酸参入量；结果：（１）分离培养的贮脂细胞完全符合该细胞的各种特征；（２）贮脂细胞是肝纤维化中细胞外基质过度沉积的重要细胞来源之一；（３）库普弗细胞可     

人肝贮脂细胞表达结蛋白的免疫细胞化学观察

用免疫细胞化学法观察了正常人肝贮脂细胞表达结蛋白中间丝。发现结蛋白阳性细胞位于血窦旁旁狄氏间隙内,呈星形或纺锤形,于肝小叶内大致均匀分布,有些细胞内含有空泡,每高倍(400X)视野细胞数为15～25个。汇管区结缔组织内及肝静脉周围散在少数与小叶内形态相似的结蛋白阳性细胞。结果表明正常人肝贮脂细胞表达结蛋白,可作为研究该细胞的良好标志,并支持了贮脂细胞的肌源性学说。[关键词]贮脂细胞,结     

大鼠肝大部切除后再生时贮脂细胞的动态变化

目的 研究大鼠肝大部切除后再生时贮脂细胞的动态变化。方法 用结蛋白免疫组织化学法显示肝贮脂细胞并计量，以图像分析仪测灰度值。结果 正常肝小叶内贮脂细胞呈网架状分布，肝大部切除后再生时贮脂细胞数量递减，至第５ｄ时为正常肝的１／３。结论肝大部切除后再生时贮脂细胞动态变化明显不同于肝中毒等损伤后的增殖变化。     

细胞因子对贮脂细胞增殖的调控

通过有关人肝纤维化及培养大鼠和人的贮脂细胞的实验研究,已证实贮脂细胞在肝纤维化形成中起重要作用。在纤维化发生过程中,贮脂细胞由一种静止的含有丰富维生素Ａ的表型转化为肌纤维母细胞样。与静止的贮脂细胞相比,肌纤维母细胞样贮脂细胞（ＭＦＩＣ）具有更高的增殖...     

肠源性内毒素血症在实验性肝纤维化发生发展中的作用

目的和方法：利用复合因子（以四氯化碳为主要因素）致大鼠肝纤维化模型，探讨肠源性内毒素血症在肝纤维化发生发展中的作用。结果：（１）血浆内毒素水平在肝纤维化过程中逐渐升高，且与肝胶原蛋白含量变化正相关；（２）血浆ＴＮＦα测定及ＴＮＦα免疫组化定位研究，均表明ＴＮＦα参与了内毒素介导的肝纤维化过程；（３）肝组织Ⅰ、Ⅲ型胶原酶活性均在肝纤维化早期增高，晚期呈下降趋势。超微结构观察显示贮脂细胞在此过程中发生表型转化，提示贮脂细胞功能状态与内毒素在肝纤维化过程中的作用密切相关。结论：肠源性内毒素血症在肝纤维化发生发展中起重要作用     

贮脂细胞凋亡与肝纤维化逆转

贮脂细胞经过激活、刺激性增殖、表型转换后分泌大量的细胞外基质和基质金属硫蛋白酶抑制剂 (TIMPs)而在肝纤维化中发挥了关键作用。但随着贮脂细胞的激活 ,其凋亡敏感性发生改变 ,通过Fas依赖途径发生凋亡 ,其数量明显减少 ,细胞外基质合成和TIMPs的表达快速下降 ,而使肝纤维化发生逆转。这一过程涉及贮脂细胞中凋亡和抑凋亡基因的表达变化。提示通过诱导激活的贮脂细胞凋亡 ,可能为肝纤维化的逆转治疗提供一新的乐观手段。     

人慢性肝炎贮脂细胞超微形态的计量学变化

目的探讨人慢性肝炎贮脂细胞（又称肝星状细胞）的转化规律。方法利用肝穿刺活检材料，以半薄切片光镜计数及电镜形态计量学等研究方法，对人慢性迁延性肝炎（５例）、轻度慢性活动性肝炎（５例）、中度慢性活动性肝炎（６例）及重度慢性活动性肝炎（５例）的肝小叶非纤维化区和正常肝组织（８例）的贮脂细胞数量、形态及细胞器含量变化进行观察分析。结果慢性活动性肝炎组肝小叶非纤维化区内贮脂细胞总数（２８．８０±３．９６、２７．１１±３．９６、２７．２０±８．８５）个／２０００００μｍ２明显低于正常肝组（４４．７５±６．８７）个／２０００００μｍ２及慢性迁延性肝炎组（４２．４０±１０．７６）个／２０００００μｍ２；过渡细胞的百分率随病变程度加重而趋向升高；部分贮脂细胞转化为成纤维细胞。结论慢性病毒性肝炎致肝纤维化过程中，贮脂细胞不断向成纤维细胞转化，并有向肝小叶纤维间隔迁移的趋势     

肝贮脂细胞及其在慢性病毒性肝炎中的变化和作用

肝贮脂细胞具有合成胶原的能力,受损伤时,贮脂细胞可转化为纤维母细胞。基于这些特点,Popper提出贮脂细胞在肝纤维化过程中起重要作用。以后,McGee和Mak分别从不同的动物实验证实了贮脂细胞在四氧化碳和洒精中毒所引起肝纤维化过程中的作用。本文以慢性病毒性肝炎病例的肝活检组织为对象,研究贮脂细胞的变化,并结合文献探讨其在慢性病毒性肝炎发病过程中的作用。材料和方法肝穿刺活检组织来自北京医科大学第一附属医院传染科、中国人民解放军261和262医院传染科。每例肝穿刺组织分成     

丙型肝炎的病理观察

为确立我国丙型肝炎病理形态学特点，我们观察了７０例经临床确诊的丙型肝炎肝穿标本，其中８９％有输血及血制品使用史。按病程分为急性丙型肝炎２０例，慢性丙型肝炎５０例，其中合并乙型肝炎者７例。与乙型肝炎相比，丙型肝炎特征的组织学改变有：汇管区淋巴细胞集聚、小胆管损伤及较明显的肝细胞脂变。此外，急性丙型肝炎尚见片状的肝细胞明显大小不等，伴大泡脂变。慢性丙型肝炎伴小胆管损伤淋巴细胞集聚，以Ｔ细胞为主，致汇管区扩大为其特征。中度以上慢性活动型丙型肝炎常见宽大的汇管区－汇管区桥接坏死及纤维化，碎屑坏死相对较轻。本研究为丙型肝炎的病理诊断及与乙型肝炎的鉴别诊断提供了依据。     

细胞因子在肝纤维化中的作用

根据单个细胞因子对贮脂细胞增殖、转化及细胞外基质合成的影响，将肝纤维化相关性细胞因子分为直接刺激因子、间接刺激因子和抑制因子三类；进一步从细胞和细胞因子网络的相互作用、细胞因子在肝纤维化形成的不同阶段中的作用及其作用机制等方面综述细胞因子与肝纤维化机制的研究进展。     

Immunohistochemical studies of intrahepatic tumour necrosis factor alpha in chronic liver disease.

To determine the intrahepatic production of tumour necrosis factor alpha (TNF alpha) in chronic liver disease three monoclonal antibodies were used against TNF alpha in immunohistochemical studies of liver tissue sections from patients with chronic liver disease. All three monoclonal antibodies stained infiltrating mononuclear cells. Monoclonal antibody II 7C2 also stained the cytoplasm or nucleus, or both, of a varied number of hepatocytes from nine patients with chronic hepatitis B virus infection, suggesting that the antigenic epitope related to hepatitis B core antigen (HBcAg) crossreacted with II7C2. The other two monoclonal antibodies, III2F3 and IV3E5, stained significantly larger numbers of mononuclear cells in cases of chronic active hepatitis B than in chronic persistent hepatitis B, or hepatitis B related liver cirrhosis. III2F3 stained significantly larger numbers of mononuclear cells in non-A, non-B chronic active hepatitis than in chronic persistent hepatitis B or hepatitis B related liver cirrhosis. These results indicate that TNF alpha is produced and secreted by infiltrating mononuclear cells in focal inflammatory areas of the liver, and suggest that TNF alpha may have a role in the inflammatory activity of chronic liver disease.     

Studies on lymphocytotoxicity in acute and chronic liver disease

The cytotoxicity of lymphocytes from patients with chronic active hepatitis, chronic persistent hepatitis, acute hepatitis B and rheumatoid arthritis as well as from normal controls was studied in a microcytotoxicity assay according to COHEN et al. using 125I-iododeoxyuridine labeled embryonal liver cells and Chang cells as target cells. Unfractionated lymphocytes of the peripheral blood from patients with chronic active hepatitis and rheumatoid arthritis showed a high frequency of cytotoxic activity. The lymphocytotoxicity in chronic active hepatitis was significantly increased in comparison to normal controls at the EC/TC of 10:1 and 100:1. Specificity of the cytotoxic reaction to target cells could not be demonstrated. Addition of autologous serum to the cytotoxic assay blocked the lymphocytotoxicity in patients with chronic active hepatitis. A weak potentiating effect on lymphocytotoxicity was observed in patients with hepatitis B after addition of autologous serum. It is discussed that this reaction is due to the presence of HB-antigen in the serum since addition of HB-antigen from other sources increased also the lymphocytotoxicity in hepatitis B patients. This effect was observed neither in HB-antigen positive nor in HB-antigen negative patients with chronic active hepatitis or chronic persistent hepatisis.     

原发性肝癌和慢性肝病血清HBsAg特异性免疫复合物的检测比较

采用捕捉法ELISA,检测31例HBV感染指标阳性的原发性肝癌患者血清四类HBsAg特异性免疫复合物。结果表明,各类的阳性率均非常显著低于慢性活动性乙肝和乙肝后肝硬化,而与慢性迁延性乙肝无明显差异。提示患者的免疫抑制程度与慢迁肝基本一致。     

Chronic viral hepatitis B and C: an argument against the conventional classification of chronic hepatitis

The classification of chronic hepatitis distinguishing benign chronic persistent hepatitis from severe chronic active hepatitis was constructed without knowledge of well-defined aetiological factors. Better understanding of the different hepatitis-viruses has shed new light on this subject. Chronic viral hepatitis B and C each show typical histological patterns. The validity of the conventional classification has been evaluated by a comparative study of chronic viral hepatitis B and C. 130 biopsies from 110 patients with chronic hepatitis C (CH-C) proven serologically by antibodies (second generation testing) were compared with 105 biopsies from 73 patients with chronic hepatitis B (CH-B). These were scored semi-quantatively. In CH-C, lymphoid follicles and/or aggregates were found in 88.5%, fatty degeneration in 51%, bile duct lesions in 46.2%, and Mallory body-like material in the hepatocytes in 9.2%. The portal lymphocytic infiltration generally predominated over the necro-inflammatory lesions of the parenchyma. Chronic persistent hepatitis (defined by the presence of portal hepatitis) was present exclusively in CH-C. Chronic lobular hepatitis was found exclusively in CH-B. We conclude that the histological criteria described for CH-C are highly suggestive of the diagnosis, that the artificial subdivision of chronic hepatitis into CPH and CAH is obsolete and that the histological assessment of chronic hepatitis should consist of a grading of inflammatory activity (minimal, mild, moderate, severe) and staging of fibrosis (extent of distortion of architecture). The final diagnosis should be based on the demonstration of the aetiological agent.     

树突状细胞及其Toll样受体与乙型肝炎慢性化研究进展

目前认为,机体对乙型肝炎病毒（HBV）的免疫耐受是乙型肝炎慢性化的主要原因。作为最重要的抗原呈递细胞,树突状细胞（DC）无论数量不足还是功能缺陷都将导致HBV在体内的持续感染。Toll样受体（TLR）是当前免疫学研究的热点,近年来,人们逐渐认识到慢性乙型肝炎（CHB）患者体内Dc的TLR存在表达异常,这可能是导致乙型肝炎慢性化的一个重要原因。     

树突状细胞及其Toll样受体与乙型肝炎慢性化研究进展

目前认为,机体对乙型肝炎病毒(HBV)的免疫耐受是乙型肝炎慢性化的主要原因.作为最重要的抗原呈递细胞,树突状细胞(DC)无论数量不足还是功能缺陷都将导致HBV在体内的持续感染.Toll样受体(TLR)是当前免疫学研究的热点,近年来,人们逐渐认识到慢性乙型肝炎(CHB)患者体内DC的TLR存在表达异常,这可能是导致乙型肝炎慢性化的一个重要原因.     

树突状细胞及其Toll样受体与乙型肝炎慢性化研究进展

目前认为,机体对乙型肝炎病毒(HBV)的免疫耐受是乙型肝炎慢性化的主要原因.作为最重要的抗原呈递细胞,树突状细胞(DC)无论数量不足还是功能缺陷都将导致HBV在体内的持续感染.Toll样受体(TLR)是当前免疫学研究的热点,近年来,人们逐渐认识到慢性乙型肝炎(CHB)患者体内DC的TLR存在表达异常,这可能是导致乙型肝炎慢性化的一个重要原因.     

Immunological studies of Australia antigen carriers with and without liver diseases

Examination of the cell-mediated and the humoral immune systems was carried out in two groups of persistent carriers of Australia antigen. Group A included eleven blood donors with an entirely normal liver histology and without previous history of liver disease. Group B included seven patients with an initial acute `viral' hepatitis verified by biopsy. Subsequent biopsies revealed progression to chronic persistent hepatitis in three cases, to chronic aggressive hepatitis in three, and a suspicion of chronicity in one of the patients.

The patients in group B had significantly higher serum concentration of IgM and significantly lower serum concentration of complement C4 than the healthy carriers in group A. No differences were found between the two groups with respect to the presence of autoantibodies or the antibody response to vaccination with keyhole limpet haemocyanin. Delayed-type cutaneous reactions to 2,4-dinitrochlorobenzene, haemocyanin and PPD were equal in the two groups. The PHA-induced lymphocyte transformation was significantly lower in the group of patients with chronic hepatitis as compared to the healthy carriers, but none of the groups showed a statistically significant difference from a control group of eight laboratory technicians. It is concluded that a general immunodeficiency state is not a prerequisite for developing persistent Au-antigenaemia. The slightly impaired T-cell response to PHA found in patients with persistent Au-antigenaemia and chronic liver disease may be related to the liver disease rather than to the Au-antigen carrier state.

     

慢性乙型肝炎,肝硬化患者外周血LAK细胞活性和sIL—2R测定的意义

采用＾３Ｈ－ＴｄＲ释放法测定５１例慢性肝病患者（ＣＰＨ１０例、ＣＡＨ２３例、ＬＣ１８例）外周血ＬＡＫ细胞活性，并用酶联法测定患者血清中ｓＩＬ－２Ｒ含量；与２９例正常对照组比较，发现肝病患者ＬＡＫ活性降低，ＨＢＶＤＮＡ阳性组ＬＡＫ活性较阴性组低（Ｐ〈０．０５），ｓＩＬ－２Ｒ增高，且慢性肝病组ＬＡＫ活性与ｓＩＬ－２Ｒ水平呈负相关，说明ＬＡＫ活性与机体免疫功能状态有关，ＨＢＶ的复制和高浓度的ｓＩＬ－２Ｒ