γ -谷氨酰转移酶及同工酶对肝细胞癌变的监测作用

目的 探讨γ－谷氨酰转移酶（ＧＧＴ）异常表达在监测肝细胞癌变中的价值。方法 以２－乙酰氨基芴（２－ＦＡＡ）喂饲ＳＤ大鼠诱发肝癌,观察鼠肝细胞在癌变期间的病理组织学,酶组织化学,肝总ＲＮＡ水平,不同分子主同工酶的动态改变。结果 诱癌后随鼠肝组织学改变,肝ＧＧＴ过度表达,可溶性及膜结合性ＧＧＴ比活性均明显异常;肝总ＲＮＡ浓度与肝ＧＧＴ比活性或血清ＧＧＴ活笥均呈显著正相关;     

肝癌和癌旁肝组织中IGF-Ⅰ,IGF-Ⅰ受体mRNA的表达

目的　探讨胰岛素样生长因子Ⅰ（ＩＧＦⅠ） 及其受体（ＩＧＦⅠＲ）在肝细胞癌变过程中的作用及意义．方法　采用ＤＮＡＲＮＡ 原位杂交方法观察肝癌（ ｎ ＝ ３０） 和癌旁肝组织中ＩＧＦⅠ,ＩＧＦⅠ受体ｍ ＲＮＡ 的表达．结果　在肝癌和癌旁肝组织中ＩＧＦⅠ的表达率分别为４０－０ ％和５０－０ ％ ,ＩＧＦⅠ受体的表达率分别为４６－７ ％ 和５３－３ ％ ;ＩＧＦⅠ,ＩＧＦⅠ受体在分化较差的癌细胞和不典型增生肝细胞中表达最为明显．结论　ＩＧＦⅠ和ＩＧＦⅠ受体可能在肝细胞癌变过程中发挥重要作用．     

A prospective study of vertical transmission of hepatitis C virus

ＡｐｒｏｓｐｅｃｔｉｖｅｓｔｕｄｙｏｆｖｅｒｔｉｃａｌｔｒａｎｓｍｉｓｓｉｏｎｏｆｈｅｐａｔｉｔｉｓＣｖｉｒｕｓＳＵＮＤｅＧｕｉ１，ＬＩＵＣａｉＹｕｎ１，ＭＥＮＧＺｏｎｇＤａ２，ＳＵＮＹｏｎｇＤｅ２，ＷＡＮＧＳｈｕＣｏｎｇ１，ＹＡＮＧＹｕ...     

熊脱氧胆酸促进肝脏部分切除后肝细胞再生

目的 探讨熊脱氧胆酸（ｕｒｓｏｄｅｏｘｙｃｈｏｌｉｃ ａｃｉｄ，ＵＤＣＡ）对胆道梗阻肝脏部分切除（ＰＨ）后肝细胞再生的影响。方法Ｗｉｓｔａｒ大鼠随机分为正常７０％肝部分切除组（Ｎ－ＰＨ）、胆道梗阻２周７０％ＰＨ组（ＢＤＯ－ＰＨ）、ＢＤＯ—ＰＨ ＵＤＣＡ治疗组及ＢＤＯ—ＰＨ生理盐水治疗组。观察肝组织学改变，检测７０％ＰＨ后肝细胞ＢｒｄＵ标记、肝内肝细胞生长因子（ＨＧＦ）及其受体Ｍｅｔ ｍＲＮＡ表达。结果 ＵＤＣＡ治疗能促进胆道梗阻后肝功能好转并减轻肝组织学病变；ＵＤＣＡ治疗组大鼠７０％ＰＨ后肝内ＨＧＦ／Ｍｅｔ ｍＲＮＡ高峰表达值均高于ＢＤＯ—ＰＨ组（Ｐ ＜ ０．０５），肝细胞 ＢｒｄＵ高峰标记指数（５９．３９±１０．８２）％高于 ＢＤＯ—ＰＨ组肝细胞 ＢｒｄＵ高峰标记指数（３６．２２±８．３７％（ｔ＝４．１４９，Ｐ＜０．０１），而与Ｎ－ＰＮ组肝细胞ＢｒｄＵ高峰标记指数（６８．６４±１１．２６％）％相比差异无显著性（ｔ＝１．４５１，Ｐ＞０．０５）。结论 ＵＤＣＡ通过缓解胆道梗阻后肝组织损害并上调７０％ＰＨ后肝内ＨＧＦ／Ｍｅｔ ｍＲＮＡ表达，从而促进胆道梗阻肝脏部分切除后肝细胞再生。     

P21 and CEA expression and AgNOR counts in DMH induced colon carcinoma in rats

Ｐ２１ａｎｄＣＥＡｅｘｐｒｅｓｓｉｏｎａｎｄＡｇＮＯＲｃｏｕｎｔｓｉｎＤＭＨｉｎｄｕｃｅｄｃｏｌｏｎｃａｒｃｉｎｏｍａｉｎｒａｔｓＺＨＡＮＧＺｈｉＧａｎｇ１，ＷＵＪｉｎｇＹｉｎｇ２，ＦＵＸｉａｎｇＤｏｎｇ２，ＧＵＤａＫｕｎ１ａｎｄＦＡＮＧＦ...     

Double-bullet radioimmunotargeting therapy in 31 patients with primary liver cancer

Ｄｏｕｂｌｅｂｕｌｅｔｒａｄｉｏｉｍｍｕｎｏｔａｒｇｅｔｉｎｇｔｈｅｒａｐｙｉｎ３１ｐａｔｉｅｎｔｓｗｉｔｈｐｒｉｍａｒｙｌｉｖｅｒｃａｎｃｅｒＷＵＹｉｎｇＤｅ１，ＺＨＯＵＤｅＮａｎ２，ＧＡＮＧＹｏｕＱｕａｎ２，ＨＵＸｉａｏＨｕａ１，ＬＩＺ...     

肝细胞癌变过程中维生素E水平改变及其作用机制研究

目的 探讨维生素Ｅ（Ｖｉｔ Ｅ）水平在肝细胞癌变过程中的改变与作用机制。方法 用２－ＦＡＡ制备大鼠肝癌动物模型,在肝细胞癌变过程中观察其肝组织学、肝总ＲＮＡ水平及血浃ＶｉｔＥ含量的动态改变,并对不同肝病患者血清中ＶｉｔＥ的浓度进行了分析。结果 在肝细胞癌变过程中,鼠血清中ＶｉｔＥ含量呈逐渐降低,而鼠肝总ＲＮＡ水平逐渐增加趋势;在急性肝炎、慢性肝炎、肝硬变和肝癌患者血清中ＶｉｔＥ含量均显著低于正常对     

甘氨脱氧胆酸激活大鼠肝细胞磷脂酶A2和对血清磷脂酶蛋白及mRNA水平的表达

实验证实甘氨脱氧胆酸（ｇｌｙｃｏｄｅｏｘ－ｙｃｈｏｌｌｃａｃｉｄ,ＧＤＣ）≥２５０μｍｏｌ／Ｌ可导致大鼠肝细胞坏死,细胞膜流动性降低［１］。磷脂酶Ａ２（ｐｈｏｓｐｈｏｌｉｐａｓｅＡ２,ＰＬＡ２）过量释放和／或激活在多系统器官衰竭的发展中起着关键作用。用ＧＤＣ处理原代培养大鼠肝细胞,以探讨ＧＤＣ对ｓＰＬＡ２酶活性的激活,酶蛋白和基因表达的影响。一、材料与方法１．主要试剂：ｓＰＬＡ２单克隆抗体由美国Ｌｉｓａ．Ａ．Ｍ教授惠赠。ＲＮＡ提取试剂购自德国宝灵曼公司。ｍａｒｋｅｒ：ｐＢＲ３２２ＤＮＡ／ＢＳｔＮ…     

细胞因子对树突状细胞抗肝癌作用的影响

目的研究人血树突状细胞（ＤＣ）和细胞因子ＴＮＦ,ＧＭＣＳＦ或ＩＦＮγ联合ＤＣ对淋巴因子和ＰＨＡ激活的杀伤细胞（ＬＰＡＫ细胞）体外杀伤人肝癌细胞株ＢＥＬ７４０２的影响．方法实验分为Ｌ组（ＬＰＡＫ）,Ｄ组（ＬＰＡＫ＋ＤＣ）,Ｔ１组（ＬＰＡＫ＋ＤＣ＋ＴＮＦ５０００ｋＵ／Ｌ）,Ｔ２组（ＬＰＡＫ＋ＤＣ＋ＴＮＦ５００ｋＵ／Ｌ）,Ｇ１组（ＬＰＡＫ＋ＤＣ＋ＧＭ－ＣＳＦ５００ｋＵ／Ｌ）,Ｇ２组（ＬＰＡＫ＋ＤＣ＋ＧＭ－ＣＳＦ１００ｋＵ／Ｌ）,Ｉ１组（ＬＰＡＫ＋ＤＣ＋ＩＦＮγ５００ｋＵ／Ｌ）和Ｉ２组（ＬＰＡＫ＋ＤＣ＋ＩＦＮγ１００ｋＵ／Ｌ）．每组效靶细胞比分别采用５∶１和１０∶１两种．培养４８ｈ后用中性红比色法检测细胞毒活性．结果Ｌ,Ｄ,Ｔ２和Ｔ１组的细胞毒活性依次增强,各组间差异有显著性（Ｐ＜００１）．Ｇ１和Ｇ２组均高于Ｄ组（Ｐ＜００１）,但Ｇ１,Ｇ２组间差异无显著性．Ｉ１,Ｉ２组与Ｄ组相比,也无显著性差异．随效靶比增加,各组细胞毒活性均相应增强．结论ＤＣ能增强ＬＰＡＫ细胞对肝癌细胞ＢＥＬ７４０２的细胞毒活性;ＴＮＦ或ＧＭＣＳＦ与ＤＣ联用,两者有协同作用;但与ＩＦＮγ联用,则无进一步增强作用     

慢性氟中毒大鼠肝脏损害机理及亚细胞部位研究

用３０ｍｇ／Ｌ，６０ｍｇ／Ｌ和１２０ｍｇ／Ｌ含氟水饲养大鼠１２周，复制慢性氟中毒动物模型，探讨肝脏损害机理和亚细胞部位、结果发现：肝损害指标肝甘油三酯（ＴＧ）含量和血清谷丙转氨酶（ＳＧＰ）活性显著升高；肝雨二醛（ＭＤＡ）含量显著升高，肝还原型谷胱甘肽（ＧＳＨ）含量显著降低；肝脂质过氧化指标变化与肝损害指标变化呈平行关系；肝线粒体和微粒体ＭＤＡ含量显著升高，其相应标志酶琥珀酸脱氢酶（ＳＤＨａｓｅ）和葡萄糖－６－磷酸酶（Ｇ－６－Ｐａｓｅ）活性显著降低，而且各亚细胞器ＭＤＡ含量升高分别与各自标志酶活性降低存在显著负相关关系。结果提示，慢性氟中毒引起肝脏损害机理之一是脂质过氧化；慢性氟中毒可致肝细胞线粒体和微粒体发生脂质过氧化损害作用。     

诱癌过程中鼠肝组织一氧化氮合酶的表达与改变

目的：研究ＮＯ合酶在肝癌发生过程中的表达与改变。方法：以化学致癌剂２－ＦＡＡ喂饲ＳＤ大鼠，对鼠肝细胞在癌变过程中的组织学改变、一氧化氮合酶（ＮＯＳ）的表达和动态变化进行了研究。结果：当肝细胞轻度损伤时，肝组织中ＮＯＳ活性与对照组相比明显下降；当肝细胞表现为癌前病变和肝细胞完全癌变时，肝组织中ＮＯＳ的合成增加其比活性仍低于正常对照鼠；肝组织中ＮＯＳ与ＮＯ水平呈明显正相关（ｒ＝０５７，Ｐ＜００１），而与总ＲＮＡ浓度无相关性。结论：研究资料提示ＮＯＳ在诱癌早期的表达处于抑制状态以对肝细胞起保护作用；而肝癌形成阶段，ＮＯＳ加速表达以杀伤肿瘤细胞     

Adenosine Deaminase Isoenzymes in Liver Disease

To clarify the clinical significance of increased serum adenosine deaminase (ADA) activity, and its mechanisms in various liver diseases, ADA isoenzyme activities (ADAI and ADA2) in serum and in peripheral blood mononuclear cells were studied. High serum ADA activities were found in patients with acute hepatitis, alcoholic hepatic fibrosis, chronic active hepatitis, liver cirrhosis, and hepatoma. The ADA2:ADA ratio was decreased in acute hepatitis, but was increased in chronic active hepatitis and liver cirrhosis. Clinically, ADA2 activity was correlated with serum γ-globulin levels. In chronic active hepatitis, total ADA activities in the peripheral blood mononuclear cells were similar to those in controls. Furthermore, ADA2 activities after phytohemagglutinin (PHA) stimulation were significantly lower than those without PHA stimulation, although total ADA activities were increased after PHA stimulation. These findings suggest that serum ADA isoenzyme activities may be a new marker for liver disease, and that the increased serum ADA2 in chronic active hepatitis is unlikely to be the result of an increase in ADA2 production by activated peripheral blood mononuclear cells.     

Honey prevents hepatic damage induced by obstruction of the common bile duct

AIM： To examine the possible effects of honey supplementation on hepatic damage due to obstruction of the common bile duct in an experimental rat model. METHODS： The study was performed with 30 male rats divided into three groups： a sham group, an obstructive jaundice group, and an obstructive jaundice plus honey group. At the end of the study period, the animals were sacrificed, and levels of nitric oxide （NO）, and NO synthase （NOS） activities were measured in liver tissues, and levels of adenosine deaminase （ADA） and alanine transaminase （ALT） activities were measured in serum.
RESULTS： Blood ALT and ADA activities were significantly elevated in the jaundice group as compared to those of the sham group. In the obstructive jaundice plus honey group, blood ALT and ADA activities were significantly decreased as compared to those of the jaundice group. In erythrocytes and liver tissues, NO levels were found to be significantly higher in the obstructive jaundice plus honey group compared to those of the sham group. Additionally, NO levels were found to be significantly higher in liver tissues from the animals in the obstructive jaundice plus honey group than those of the jaundice group.
CONCLUSION： Honey was found to be beneficial in the prevention of hepatic damage due to obstruction of the common bile duct.     

Altered biosynthesis of gangliosides in developing biliary cirrhosis in the rat.

The biosynthesis of gangliosides was studied in developing biliary cirrhosis in rats 14, 28, and 42 days after bile duct obstruction. The total content and patterns of gangliosides in livers and sera, and the activity of six hepatic ganglioside synthases in a cell-free system were determined. Up to 7-fold increased synthase activities were strictly correlated in time and extent with increased total contents of gangliosides in liver and serum. In addition, altered patterns of serum gangliosides were observed. The results clearly demonstrate that the liver is the main source of elevated serum gangliosides in biliary cirrhosis in the rat. Increased hepatic biosynthesis and the secretion of gangliosides into the serum appear to be an important pathogenetic event. Alterations of hepatic enzyme activities indicate that GL2 and GM3 synthase regulate total hepatic ganglioside content. However, certain abnormalities in ganglioside patterns which were observed in the liver and sera of cirrhotic animals can not be explained by changes in hepatic enzyme activity. They indicate additional pathobiochemical mechanisms to be involved, e.g., altered hepatocellular processing and/or impaired secretion into bile.     

实验性肝纤维化过程中间质胶原酶活性的动态变化

目的研究肝纤维化形成的各阶段肝组织及血清间质胶原酶活性的变化规律，并明确两者的关系。方法制备人血白蛋白免疫损伤性肝纤维化模型。在不同阶段留取肝组织及血清标本，测定（１）肝组织活化间质胶原酶活性（Ａ）、（２）肝组织潜在间质胶原酶活性（Ｌ）、（３）血清间质胶原酶活性（Ｓ）。结果模型组大鼠的Ａ、Ｌ、Ｓ在致敏阶段无显著变化；在尾静脉攻击中期Ａ、Ｌ．Ｓ三者均较致敏阶段明显增高，且达最高值。此后逐渐下降；但在造模后３个月时仍较致敏阶段为高。整个造模过程中Ａ／Ｌ比值无明显变化。肝组织间质胶原酶活性与血清间质胶原因活性间呈显著正相关。结论在实验性肝纤维化的发生、发展阶段肝组织及血清间质胶原酶活性均明显升高；到了肝硬化阶段，间质胶原酶活性较肝纤维化阶段下降；在肝硬化的自发逆转中，间质胶原酶活性保持在较高水平。血清间质胶原酶活性的变化可反映肝组织间质胶原酶活性的改变。     

Serum cholesterol, lecithin-cholesterol acyltransferase, and hepatic hydroxymethylglutaryl coenzyme A reductase activities of lean and obese Zucker rats

Serum cholesterol concentrations, lecithin-cholesterol acyltransferase (LCAT), and hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activities of lean and obese Zucker rats were compared. The excess serum cholesterol of the female obese rat is found to be mainly free cholesterol associated with very low-density lipoproteins, whereas that of the male obese rat is carried as cholesterol esters associated with high-density lipoproteins. The high level of serum free cholesterol in the female obese rat is not due to a deficiency in lecithin-cholesterol acyltransferase activity. This enzyme activity is found to be elevated in the male obese rat. Hepatic HMG-CoA reductase activity declines as rats mature; this observation is most apparent in obese male rats. Lean rats exhibit the normal diurnal rhythm, but mature obese rats show little diurnal variation in HMG-CoA reductase activity. Obese female rats maintain high reductase activities, but the activities of obese male rats remain low at all times. Starvation suppresses liver HMG-CoA reductase and serum cholesterol in both lean and obese female rats. Thus, an increase in hepatic cholesterol synthesis may contribute to hypercholesterolemia in the obese female Zucker rat. On the other hand, factors such as nonhepatic synthesis or a decreased cholesterol catabolism may play more important roles in maintaining high serum cholesterol in the obese male Zucker rat.     

The source of serum alkaline phosphatases in liver-tumour-bearing rats

Patients with hepatic tumours have increased serum activities of alkaline phosphatases. In order to clarify the origin of the increased enzyme activity, two experimental models of rat liver carcinogenesis were studied. In one model, the resistant hepatocyte model, the process was initiated by diethylnitrosamine (DEN, 200 mg/kg), and preneoplastic liver nodules were selected for by 2 weeks of 2-acetylaminofluorene (2-AAF, 0.02%) feeding and partial hepatectomy (PH). High activities of serum alkaline phosphatases were found in these rapidly growing nodules harvested at the peak time of nodular mass expansion. In the other model in which nodules were induced with long-term intermittent feeding of a diet containing 0.05% 2-AAF and harvested in a late stage with a low increase of nodular liver cell mass, no such increase in serum alkaline phosphatase activity was found. A similar difference was also noted when measuring the activities of the enzyme in the nodular tissue. Thus the first model showed high activities of the enzyme in the nodular tissue, while the second model had similar activities to those of the control animals. The serum levels reflected the nodular enzyme activity in both models. The tissue surrounding the nodules did not show increased enzyme activity. No difference was noted in the serum or tissue activity of transaminases. In both models the liver nodules occupied 30-50% of the liver volume. The experimental models were selected to emphasize the importance of the rate of intrahepatic mass expansion for the levels of serum alkaline phosphatase activities.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of cholesterol supplementation on antioxidant enzyme activities in rat hepatic tissues: possible implications of hepatic paraoxonase in atherogenesis

BACKGROUND AND AIM: The effects of cholesterol supplementation on antioxidant enzyme activities were investigated hepatic tissue taken from Sprague Dawley rats. METHODS AND REULTS: The study involved 14 male Sprague Dawley rats: seven fed a normal laboratory diet and seven a normal diet plus cholesterol (3.6 g/kg/day) for three months, during which blood samples were obtained to measure serum cholesterol levels. At the end of the 3-month period, the livers were surgically removed in order to measure antioxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase and paraoxonase-1). At the end of the study period, serum total cholesterol and HDL-cholesterol levels were significantly higher in the cholesterol-fed group than the control group. There were no significant between-group differences in hepatic superoxide dismutase, catalase and glutathione peroxidase activities, but there was a significant decrease in hepatic paraoxonase-1 activity in the cholesterol-fed group. CONCLUSIONS: Cholesterol supplementation significantly decreases paraoxonase-1 activity in rat liver tissue without changing the activities of other antioxidant enzymes. These results suggest that cholesterol significantly suppresses hepatic paraoxonase-1 synthesis. It seems that the decreased paraoxinase-1 activity in the plasma HDL-fraction of atherosclerotic patients is associated with suppressed liver synthesis. A reduction in paraoxonase-1 activity may therefore lead to the more intensive exposure of LDL to oxidant attacks.