Role of intrasplenic hepatocyte transplantation in improving survival and liver regeneration after hepatic resection in cirrhotic rats

We studied the effect of preoperative hepatocyte transplantation on the prevention of liver failure in cirrhotic rats after hepatic resection. Two groups of Lewis rats were rendered cirrhotic by i.p. injection of 1% dimethylnitrosamine and were subjected to 33% hepatectomy. Two days before the resection, 36 rats in group I received intrasplenic hepatocyte transplantation, and 25 rats in group II were given intrasplenic injection of normal saline as a control. By the end of the third postoperative day, the rats in group I had better survival and a better biochemical profile than those in group II. The liver growth rate and the labeling index of proliferating cell nuclear antigen (PCNA-LI) showed a steady rise in group I. Compared with group II, group I had a significantly lower transforming growth factor (TGF-beta1) level (p < 0.05). We conclude that preoperative intrasplenic hepatocyte transplantation improves survival and facilitates regeneration in cirrhotic rats after hepatic resection.     

Liver cirrhosis in rats: regeneration and assessment of the role of phenobarbital

A common model for producing experimental liver cirrhosis is the administration of CCl4 to phenobarbital (PhB)-stimulated rats. However, concern may arise due to the complex actions of PhB upon liver metabolism. This study examined the role of PhB in the production of CCl4-induced liver cirrhosis in the rat. In addition, regenerative capacity of the liver after partial hepatectomy (PH) or portal branch ligation (PBL) was studied in cirrhotic rats, rats treated with CCl4 alone, and in PhB-treated controls. In rats given PhB throughout the CCl4-induction period, ascitic form of micronodular cirrhosis was found in 93% with only 3% mortality. In contrast, rats pretreated with PhB for only 2 weeks followed by CCl4 alone for 18 weeks did not develop liver cirrhosis. In most of the cirrhotic rats, PH induced hepatic regeneration associated with improved liver histology. PBL was less effective. Treatment with PhB alone for 10 weeks resulted in liver atrophy and reduced hepatic regenerative capacity. Impaired regeneration response was also found in rats treated with CCl4 alone. In conclusion, treatment with PhB throughout the CCl4-induction period seems necessary for the production of liver cirrhosis in rats. However, prolonged treatment with PhB alone results in liver atrophy and an impaired regenerative response. Therefore, though necessary for the cirrhotic model, PhB by itself has negative hepatotrophic influences which questions the thoroughness of the PhB/CCl4 experimental model.     

应用重组人生长激素治疗肝硬化腹水大鼠的实验研究

目的探讨应用重组人生长激素(rhGH)对肝硬化腹水大鼠的治疗作用。方法应用四氯化碳皮下注射方法复制大鼠肝硬化模型,60只清洁级雄性SD大鼠随机分为正常对照组(A组),肝硬化 生理盐水注射组(B组),肝硬化 rhGH注射组(C组)。结果 C组大鼠肝功能逐渐好转,腹水消失,生长激素抵抗现象被扭转。结论应用rhGH可以显著改善肝功能,促进腹水消退,且持续时间较长。     

肝细胞、胰岛细胞肝内移植对肝硬变影响的研究

目的避免脾切除、门腔分流术后所致向肝血流减少造成的肝功能损害。方法白蛋白将分离纯化的肝细胞、胰岛细胞经肝动脉灌注肝内移植。结果细胞组与对照组比较血总蛋白、白蛋白、胆红素改善程度,差异有极显著意义（Ｐ＜０．０１）。肝纤维化光镜检查及Ⅰ、Ⅲ型胶原免疫组织化学染色及图象分析结果,差异有显著意义（Ｐ＜０．０５）。结论肝细胞、胰岛细胞经肝动脉灌注肝内移植,不但能改善肝功能,还能促进肝脏胶原纤维降解,逆转肝纤维化、肝硬变的程度。     

同种异体肝细胞移植促进大鼠肝纤维化逆转

目的 探讨肝细胞移植对大鼠肝纤维化的改善作用及其机制.方法 经腹腔注射四氯化碳制备的肝纤维化Wistar大鼠接受正常Wistar大鼠肝细胞移植(实验组),另以不接受肝细胞移植的肝纤维化大鼠(肝纤维化组)和接受肝细胞移植的正常Wistar大鼠(移植对照组)为对照.肝细胞移植于注射四氯化碳后21 d进行.分别于移植前及移植后第1、2、7和14天采集抗凝血(肝纤维化组同步采集),测定血浆总转化生长因子β1(TGF-β1)、活性TGF-β1、纤溶酶及α2-巨球蛋白(α2M)水平,并取其肝脏,进行肝脏的纤维成像和定量分析,检测肝脏星形细胞活性.结果 肝细胞移植后的第14天,实验组肝脏内成胶原纤维面积百分比为(3.69±0.44)%,低于肝纤维化组的(8.25±0.69)%(P＜0.01);实验组肝内α-SMA阳性信号面积百分比为(0.43±0.03)%,明显低于肝纤维化组同期的(2.79±0.40)%(P＜0.01).移植前实验组大鼠血浆中总TGF-β1和活性TGF-β1水平分别为(4543.2±307.2)μg/ml和(2380.7±150.8)μg/ml,移植后1 d,二者均显著下降,分别为(2109.9±425.2)μg/ml(P＜0.01)和(1758.9±429.2)μg/ml(P＜0.05).实验组肝细胞移植前血浆纤溶酶水平为(5.16±0.42)μg/ml,移植后下降至(2.96±0.11)μg/ml(P＜0.01).实验组肝细胞移植前血浆α2M水平为(152.4±27.6)mg/ml,移植后升高至(343.0±48.8)mg/ml,为移植前的2倍,而移植对照组的α2M水平移植后升高30余倍.结论 肝细胞移植能有效改善大鼠肝纤维化,其机制可能与肝内活性星形细胞减少及TGF-β1水平降低有关.     

CTLA4-Ig对肝细胞移植大鼠免疫耐受的作用及其机制

目的 探讨细胞毒性淋巴细胞相关抗原4融合蛋白(CTLA4-Ig)诱导肝细胞移植大鼠免疫耐受的作用及机制.方法 10%D-氨基半乳糖(D-gal)一次性腹腔注射建立大鼠急性药物性肝衰竭模型;采用肝脏原位灌注法分离纯化肝细胞,经脾脏移植后随机分为两组.实验组腹腔一次性注射CTLA4-Ig,对照组不予处理.两组均分别于术后第1、3、5、7天采外周血观察白细胞介素(IL)-2、肿瘤坏死因子(TNF)及肝功能变化;术后1周测两组大鼠外周血T细胞亚群,处死大鼠后取脾脏苏木素-伊红(HE)染色.结果 实验组谷丙转氨酶(ALT)、血清总胆红素(TBil)于术后第7天分别为(6.5±7.3)IU/ml、(5.1±1.6)mmol/L,低于对照组.术后治疗组IL-2含量明显下降,第7天达到(1. 3138±0.8508)ng/L,两组差异有统计学意义(P＜0.05);术后TNF含量两组之间差异无统计学差异(P＞0.05).外周血CD4+T细胞、CD4+/CD8+T细胞实验组分别为(37.3±7.2)%、(1.5±0.1)%,低于对照组(P＜0.05),CD8+T细胞两组差异无统计学意义(P＞0.05).术后第7天治疗组脾内仍可见肝细胞或肝细胞团,对照组见大量淋巴细胞浸润,但很少见肝细胞.结论 CTLA4-Ig能诱导经脾同种异体肝细胞移植大鼠免疫耐受,使急性肝衰大鼠肝功能得到改善.可能是抑制T淋巴细胞亚群,且主要是抑制CD4+T细胞,使CD4+/CD8+T细胞比值下降;抑制IL-2的分泌.

Abstract：

Objective To investigate the immunosuppressive effect of cytotoxic T Iymphocyte associated antigen 4 Ig fusion protein (CTLA4-Ig) in rat allograft hepatocyte transplantation model and the mechanisms. Methods Acute liver failure (ALF) model was established by intraperitoneal injection of 10% D-gal solution to SD rates. Collagenase perfusion was performed on SD rats to separate liver cells. SD rats with ALF were subjected to intrasplenic hepatocyte transplantation and randomly divided into two groups. The experimental group received intraperitoneal injection of CTLA4-Ig. The concentrations of interleukin (IL)-2 and tumor necrosis factor (TNF), liver function and histologicy were observed at the 1st,3rd, 5th, 7th day after operation and the T lymphocyte subsets were detected by using immunohistochemistry at the 7th day after operation. Results The levels of ALT and TBil were respectively (6. 5 ±7.3) IU/ml and (5.1 ± 1.6) mmol/L at the 7th day after operation and significantly decreased after injection of CTLA4-Ig ( P ＜ 0. 01 ). IL-2 concentration in the experimental group was ( 1.3138 ± 0. 8508 ) ng/L at the 7th day after operation and significantly decreased (P ＜0. 05). TNF had no significant difference between two groups after operation ( P ＞ 0. 05 ). T lymphocyte subsets, mainly CD4 + , in the experimental group was significantly decreased as compared with control group ( P ＜ 0. 05 ), so did the CD4 +/CD8 +. Histological changes: At the 7th day after operation, there were some hepatocytes in the spleen of the experimental group. But in the control group, the changes in the spleen were characterized by severe lymphocyte infiltration. There were no hepatocytes both groups. Conclusion CTLA4-Ig can induce rat allogeneic hepatocytes intrasplenic transplantation immune tolerance. It may improve the liver function of rats with ALF.CTLA4-Ig can decrease T lymphocyte subsets, mainly CD4 + and concentrations of IL-2.     

内皮祖细胞移植对大鼠肝硬化作用的研究

目的 探讨内皮祖细胞(endothelial progenitor cells,EPCs)移植对四氯化碳(carbon tetrachloride,CCl4)诱导的大鼠肝硬化的作用.方法 本组38只SD大鼠中8只大鼠为正常对照,其余30只采用25%的CCl4/橄榄油灌胃制备肝硬化模型.再将肝硬化大鼠分为3组,每组10只.12周后直接处死的为肝硬化模型组,门静脉输入大鼠EPCs为EPCs移植组,经门脉输入生理盐水为移植对照组.移植4周后检测移植组和移植对照组大鼠肝组织胶原Ⅲ(collagen Ⅲ,COL Ⅲ)、平滑肌动蛋白(smooth muscle actin α,α-SMA)和Ki67的表达,检测外周血肝功能和血凝分析.结果 肝硬化模型组大鼠肝脏体积增至正常时的2倍.EPCs移植组大鼠与肝硬化模型组比较,肝组织学活动指数(histological activity index,HAI)(F=75.062,P<0.01),丙氨酸氨基转移酶(alanine aminotransferase,ALT)(F=29.942,P<0.05),门冬氨酸氨基转移酶(aspartate aminotransferase,AST)(F=16.618,P<0.05)和总胆红素(total bilirubin,TBIL)(F=9.911,P<0.05)水平降低,白蛋白(albumin,Alb)(F=4.944,P<0.05)和Ki67(F=45.966,P<0.01)水平升高,纤维化面积(F=25.025,P<0.05)减少,α-SMA(F=7.86,P<0.05)和COL Ⅲ(F=135.787,P<0.01)表达降低;与正常肝脏相比,移植对照组HAI,ALT,AST和TBIL水平升高,Alb和Ki67水平降低,纤维化面积增加,α-SMA和COL Ⅲ表达升高(P<0.05).移植对照组大鼠凝血酶原时间延长,差异有统计学意义(P<0.05). 结论移植EPCs可以促进大鼠肝硬化的肝细胞增生,减轻肝纤维化程度.     

Thioacetamide- and carbon tetrachloride-induced liver cirrhosis

Two methods of inducing liver cirrhosis in the rat were studied. Intragastric administration of CCl4 for 16 weeks according to Proctor and Chatamra was compared to the administration of thioacetamide in the drinking water (0.3 g/l) for the same period. CCl4 administration induced micronodular cirrhosis in 6/8 animals with a 27% mortality. Thioacetamide induced cirrhosis in 6/8 animals without mortality. The histologic pictures differed somewhat in that the CCl4 group exhibited more necrosis and cellular swelling while the thioacetamide group had more nuclear atypias and proliferation. Biochemically both groups had elevated plasma levels of aspartate aminotransferase. The lysosomal enzyme beta-hexosaminidase (beta-NAG) showed a transient increase in the thioacetamide animals, while beta-glucuronidase decreased. CCl4-induced cirrhosis led to an increase in beta-NAG. Plasma zinc decreased in both groups as well as liver zinc content in the CCl4 group, while there was a continuous elevation of liver zinc in the thioacetamide group. We conclude that oral administration of thioacetamide is a simple and reliable method of inducing experimental liver cirrhosis. The differences in histological appearances and some biochemical parameters may be caused by the different mechanisms of action of thioacetamide and CCl4.     

肝硬化鼠肝移植后早期全身和内脏血流动力学的变化

目的 观察正常鼠肝移植及及肝硬化鼠肝移植术早期全身和内脏血流动力学的变化。方法 实验动物随机分为正常鼠（NL,10只）、肝硬化鼠（IHPH,10只）、正常鼠肝移植（NL－OLT,9只）、肝硬化鼠肝移植（IHPH－OLT,16只）组。分别采用放射性微球法行血流动力学研究。结果 NLOLT鼠绝大多数血流动力学参数与NL鼠比较差异无显著意义。IHPH及IHPH－OLT 3d,7d组心输量和内脏血流量和内脏血流量增加,平均动脉压、周围血管总阻力和内脏血管阻力降低。内脏血流动力学紊乱较全身明显。结论 肝硬化鼠肝移植后的血流动力学紊乱可能与移植前已存在的病理生理因素有关。     

Intrasplenic transplantation of encapsulated genetically engineered mouse insulinoma cells reverses streptozotocin-induced diabetes in rats

Pancreatic islet transplantation is limited by shortage of donor organs. Although beta-cell lines could be used, their secretion of insulin is characteristically glucose independent and immunoisolation is required. Here we show that intrasplenic transplantation of encapsulated glucose-responsive mouse insulinoma cells reversed streptozotocin (STZ)-induced diabetes in rats. MIN-6 cells derived from a transgenic mouse expressing SV 40 large T antigen in pancreatic beta-cells were transfected with minigene encoding for human glucagon-like-peptide-1 under the control of rat insulin promoter. The cells were encapsulated in alginate/poly-L-lysine and used for cell transplantation in STZ-diabetic rats. Rats with nonfasting blood glucose (n-FBG) greater than 350 mg/dl were used. In group I rats (n=6) 20 million encapsulated cells were injected into the spleen. Group II rats (n=6) received empty capsules. n-FBG was measured biweekly. After 4 and 8 weeks, an intraperitoneal glucose tolerance test (IPGTT) was performed in group I; normal rats served as controls. Plasma insulin level was measured every other week (RIA). After 8 weeks, spleens were removed 1 day before sacrifice. In rats transplanted with cells the n-FBG was 100-150 mg/dl until the end of the study. After splenectomy, all cell recipients became diabetic (glucose 400 +/- 20 mg/dl). Transplanted rats showed increase in body weight and insulin production (3.3 +/- 1.0 ng/ml versus 0.92 +/- 0.3 ng/ml; p < 0.01) and had normal IPGTT. Spleens contained capsules with insulin-positive cells. Overall, data from this work indicate that intrasplenic transplantation of xenogeneic encapsulated insulin-producing cells without immunosuppression reversed diabetes in rats. Excellent survival and function of the transplanted cells was due to the fact that the cells were separated from the bloodstream by the immunoisolatory membrane only and insulin was delivered directly to the liver (i.e., in a physiological manner).     

New model of liver regeneration induced through use of vascular endothelial growth factor

INTRODUCTION: Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen. The objective of this study was to verify the proregenerative effects of VEGF in an experimental model of acute liver failure. MATERIALS AND METHODS: Sixty four rats that underwent intraperitoneal injection of carbon tetrachloride (CCl(4)) were randomly divided into two groups: group B animals received intravenous injection of VEGF(164) 1 hour following CCl(4) poisoning. Group A hosts were untreated. To obtain daily liver function tests (LFTs) and histological samples, on each day up to 8 days we sacrificed four rats in each group. RESULTS: The laboratory examinations showed notable alteration of LFTs in group A, while group B revealed only slight changes. The histological examination showed greater liver damage in group A compared with group B. CONCLUSION: Our results suggest that administration of exogenous VEGF protects the liver from CCl(4)-induced acute hepatic failure. Further studies are underway to assess whether exogenous VEGF is effective in other liver injuries.     

Resource utilization and outcome of liver transplantation for alcoholic cirrhosis. A case-control study.

Liver transplantation for alcoholic cirrhosis remains controversial at some transplantation centers. We compared resource utilization and outcome in alcoholic and nonalcoholic cirrhotic patients undergoing liver transplantation. Data were collected from 56 patients who underwent transplantation for alcohol-related cirrhosis from August 1985 to February 1991 and compared with data from a control group matched for age, sex, Child-Pugh class, and date of transplantation. No significant differences were noted in the resource utilization variables examined or in outcome (as assessed by indicators of early graft function, frequency of sepsis, incidence of rejection, renal function, and retransplantation rate). One-year survival was not significantly different (75% for the alcoholic cirrhotic group vs 76% for the nonalcoholic cirrhotic group). We conclude that liver transplantation for end-stage alcohol-related cirrhosis provides excellent results and that resource utilization appears to be equivalent to that for patients undergoing transplantation for non-alcohol-related cirrhosis.     

Therapeutic significance of Y-27632, a Rho-kinase inhibitor,on the established liver fibrosis

BACKGROUND: Recently, we demonstrated that Y-27632, a Rho-kinase inhibitor, inhibited hepatic stellate cells (HSCs) activation in terms of cellular morphology, improved the progression of carbon tetrachloride (CCl(4))-induced rat liver fibrosis. The objective of the present study was to investigate the effects of Y-27632 on the established liver fibrosis. METHODS AND METHODS: Liver cirrhosis was induced by intragastric administration of CCl(4) once a week for 12 weeks. After the first 6 weeks of CCl(4) injection, Y-27632 (30 mg/kg body weight) or saline was continuously administered to the rats via an intraperitoneally implanted osmotic pump during the final 6 weeks of CCl(4) injection. Two days after the last CCl(4) injection, 70% hepatectomy was performed. RESULTS: Y-27632 prevented the development of CCl(4)-induced liver fibrosis and improved the fibrotic changes, hydroxyproline content, and serum hyaluronic acid level in the liver. Moreover, Y-27632 reduced the number of smooth muscle alpha-actin- and transforming growth factor beta1-positive cells, and inhibited the expression of Na(+)/Ca(2+) exchanger mRNA which was reported to be an indicator of HSCs activation and liver fibrosis. Further, the Y-27632-treated group showed markedly increased survival rate after hepatectomy. CONCLUSIONS:These findings indicated that Y-27632 may be useful therapeutically in liver cirrhosis.     

增殖细胞核抗原在判断肝再生中的作用及奥美拉唑的促肝再生作用

目的　研究增殖细胞核抗原 (PCNA)计数在判断肝组织再生过程中的作用以及质子泵抑制剂奥美拉唑在肝部分切除术中对肝再生的促进作用。方法　取成年SD大鼠 5 0只 ,制备成肝硬化模型 ,随机分为对照组及处理组 ,全身麻醉下行 70 %肝切除术 ,术后按组给予生理盐水 1ml/kg·d及奥美拉唑 0 2mg/kg·d皮下注射共 1周。 1周后每组取 8只大鼠抽取静脉血样、取下肝脏称重 ,并制备肝组织光学显微镜、电子显微镜及PCNA染色标本。两周后 ,余下 6只大鼠同样处理。结果　在治疗 1周后 ,奥美拉唑组血清胃泌素水平为 (415± 2 2 )ng/L ,而治疗前为 (312± 7)ng/L ;而对照组治疗前后差异有显著意义 (P <0 0 5 )。在 1周后 ,奥美拉唑组的再生肝相对肝重量为 (6 4± 7) % ,对照组为(5 5± 6 ) % (P <0 0 5 )。治疗 2周后 ,奥美拉唑组的再生肝相对肝重量 (RLW)为 (6 9± 6 ) % ,对照组为(6 2± 5 ) % ,同样差异有显著意义 (P <0 0 5 )。肝细胞有丝分裂指数 (MI)在奥美拉唑组与对照组分别为 (2 0± 0 3) %及 (1 1± 0 2 ) %。PCNA阳性计数奥美拉唑组及对照组分别为 9 2 %及 4 1%(P <0 0 5 )。结论　PCNA在判断肝再生时与RLW及MI等指标一致 ,奥美拉唑可促进肝硬化肝部分切除术后肝脏的再生。     

骨髓单个核细胞经门静脉移植对大鼠肝纤维化的减轻作用

目的 对比研究骨髓单个核细胞经门静脉移植治疗大鼠肝硬化的疗效,为临床应用提供依据.方法 采用四氯化碳(CCl4)综合法制作Wisrar大鼠肝硬化模型,8周后经病理检查证实成模者共20只进入实验.随机分为治疗组和对照组,每组10只,两组大鼠分别经门静脉注入骨髓单个核细胞和等体积的肝素生理盐水.各组大鼠继续皮下注射CCl4(CCl4使用方法与前述造模方法相同),在原环境下继续饲养4周后处死.切取肝组织分别作HE及Masson染色.疗效评价指标包括:①一般情况;②肝脏羟脯氨酸和胶原纤维含量;③肝纤维化病理学分级.结果 (1)治疗组大鼠一般情况改善;对照组无明显改变.(2)治疗组与对照组中肝脏羟脯氨酸含量分别为(0.50±0.12)g、(0.59±0.34)g;胶原纤维含量百分数分别为(3.75±0.98)%、(5.02±0.44)%.两组之间各指标均有统计学差异(P<0.05).(3)治疗组肝纤维化病理分级也有下降,治疗前后差异明显(P<0.05),而对照组无明显变化.表明治疗组行骨髓单个核细胞移植后大鼠肝纤维化程度减轻.结论 骨髓单个核细胞肝内移植能改善大鼠肝纤维化程度,为临床肝硬化的治疗带来了新的手段.     

Effects of long-acting superoxide dismutase on liver metabolism after major hepatic resection in rats with cirrhosis

The aim of this study is to clarify the liver metabolic changes after major hepatic resection. The survival rate after 70% hepatectomy of rats with cirrhosis was significantly depressed compared with that of the control group. Mitochondrial function in the cirrhotic liver was disturbed compared with the control group. Tissue levels of hypoxanthine and xanthine increased both in the cirrhotic group and the control group. The increase in xanthine levels was remarkable and was prolonged in the cirrhotic group compared with the control group. Decreases in adenine nucleotides were observed after resection both in normal and cirrhotic livers. These were remarkable and were prolonged in rats with cirrhosis. Administration of polyoxyethylene-modified superoxide dismutase improved the survival rate and lessened decreases in adenine nucleotide levels. Moreover, it accelerated the recoveries of serum glutamic oxaloacetic and pyruvic transaminase levels after resection in rats with cirrhosis. These results indicate that disturbances in energy metabolism and increases in oxygen free radical formation are more remarkable in the cirrhotic liver than in the normal liver, which contributes to a low survival rate in rats with cirrhosis.     

肝癌合并肝硬化时脾脏对机体免疫状态影响的实验研究

目的 建立大鼠肝硬化肝癌模型，并行脾脏切除，探讨脾脏在肿瘤免疫中的作用。方法 将健康雄性SD大鼠55只背部皮下注射40％四氯化碳（CCl4)花生油溶液建立肝硬化模型，将Walker-256癌肉瘤接种于肝脏内并行脾切除术，2周后观察肿瘤的生长、转移、腹水、NK细胞活性及CD25。结果 切脾组腹水量、肿瘤转移较对照组明显，肿瘤体积明显大于对照组（P＜0.01)，荷瘤后2周两组NK细胞活性均较荷瘤前降低（P＜0.01)，而荷瘤前与荷瘤后切脾组与模拟切脾组之间比较无统计学差异（P＞0.05)。荷瘤2周后两组动物CD25较荷瘤前升高（P＜0.01)，而荷瘤前后切脾组与对照组之间比较无变化（P＞0.05)。结论 荷瘤早期切除脾脏加速肿瘤的生长、转移，而对NK细胞活性及CD25的表达影响不及肿瘤对其的影响。     

Liver cirrhosis induced by carbon tetrachloride and the effect of superoxide dismutase and xanthine oxidase inhibitor treatment.

Repeated administration of carbon tetrachloride (CCl4) induces liver cirrhosis, possibly because it involves the production of free radicals. In order to evaluate the effect of free radical scavengers such as superoxide dismutase (SOD) and allopurinol in the pathogenesis of liver cirrhosis, rats were subjected to repeated CCl4 administration with and without scavengers. Four groups of animals were studied: CCl4 plus SOD (group 1), CCl4 plus allopurinol (group 2), CCl4 alone (group 3) and olive oil (group 4, normal controls). Analysis of plasma and tissue concentrations of trace elements was performed and histopathological patterns were studied in all groups after 7 weeks of repeated intraperitoneal administration of the solutions. Plasma levels of zinc and selenium were significantly lower in all experimental groups, with reciprocal elevation of manganese and copper. Copper and manganese content in the liver tissue was significantly higher in all three experimental groups. The zinc content was elevated in groups receiving CCl4 alone (group 3) or with allopurinol (group 2). The liver selenium, however, was significantly lower in these two groups. The copper:zinc ratio for plasma was 0.78 in the control group, 1.6 in the CCl4 group, 1.3 in the allopurinol group and 1.5 in the SOD group. For liver tissue, the ratio was 0.07 for controls, 0.17 for CCl4, 0.11 for allopurinol and 0.28 for the SOD group. The changes in trace element content correlated with the severity of cellular damage observed microscopically in the liver. The higher the copper:zinc ratio, the more advanced and extensive was the microscopic evidence of liver injury after CCl4 challenge.     

HGF和SAM对慢性肝损伤大鼠肝部分切除术后肝细胞的影响

目的:比较肝细胞生长因子（HGF）和S-腺有蛋氨酸（SAM）对大鼠慢性肝损伤时肝部分切除术后肝再生和肝功能的影响,为临床应用提供依据。方法:以四氯化碳和乙醇联合诱导大鼠慢性肝损伤模型,成模后大鼠行30%肝部分切除术,然后随机分为肝硬化对照组,HGF组,SAM组,HGF+SAM组。手术当天起,肝硬化组肌内注生理盐水2 mL/d,HGF组予腹腔注射肝细胞生长因子0.65 mg/（100g·d）,SAM组予肌内注SAM20 mg/（kg·d）,HGF+SAM组同时按上述方法和剂量注射2种药物。各组大鼠分别于术后15d被处死,取血检测AST,ALT,ALB和TB; 同时在光镜及电镜下观察肝组织的病理改变及超微结构变化。结果:HGF组,SAM组,HGF+SAM组术后15 d AST,ALT,TB明显低于肝硬化组(P＜0.05),ALB水平明显高于肝硬化组(P＜0.05); 而HGF组,SAM组,HGF+SAM组3组之间无统计学差异。结论:肝硬化的大鼠肝脏行部分肝切除术后,肝功能及肝储备功能均有一定程度的受损,肝脏再生亦有障碍。HGF和SAM都可促进术后肝细胞再生。     

上消化道出血史对肝移植治疗肝硬化门静脉高压的疗效分析

目的探讨上消化道出血史对肝移植治疗肝硬化门静脉高压(PHT)疗效的影响。 方法回顾性分析2005年1月至2017年9月中国人民解放军联勤保障部队第九○○医院肝胆外科因肝硬化PHT行肝移植的受者临床资料，根据肝移植术前是否出现上消化道出血将其分为出血组和非出血组。观察指标为受者性别、年龄、术中出血量和输血量、住院时间、住院费用和肝移植前后肝功能指标。采用Wilcoxn符号秩和检验比较出血组与非出血组年龄、术中出血量和输血量等指标，采用成组t检验比较两组术前ALT、AST、总胆红素(TBil)、白蛋白(ALB)和凝血酶原时间(PT)，采用两因素重复测量资料方差分析比较两组术后1周内各时间点肝功能指标，采用卡方检验比较两组性别和原发病情况。P<0.05为差异有统计学意义。 结果最终纳入80例因肝硬化PHT接受肝移植治疗的受者，其中男性61例，女性19例，年龄7～71岁。原发病：乙型病毒性肝炎后肝硬化71例，胆汁性肝硬化5例，肝豆状核肝硬化2例，酒精性肝硬化2例。所有受者均采用原位下腔静脉逆灌注肝移植术。出血组(39例)与非出血组(41例)受者性别、年龄、原发病情况、术前肝功能指标、术中出血量和输血量、住院费用及住院天数差异均无统计学意义(P均>0.05)。出血组与非出血组术后各时间点ALT、AST、TBil、ALB和PT差异均无统计学意义(P均>0.05)。两组术后第3、5和7天血清ALT水平均低于术后第1天，两组术后第5和7天血清ALT水平均低于术后第3天，非出血组术后第7天血清ALT水平低于术后第5天(P均<0.05)。 结论肝移植前是否存在上消化道出血史对肝移植治疗肝硬化PHT受者移植术后早期肝功能无影响。