生长激素、肝细胞生长因子和烟酰胺对人胎胰岛细胞的增殖作用

目的研究生长激素(GH)，肝细胞生长因子(HGF)和烟酰胺(NIC)对体外培养的人胎胰岛细胞的增殖作用及其交互作用。方法采用La(2^7)正交设计法在体外培养的人胎胰岛细胞的各组中分别加入不同浓度及组合的GH，HGF和NIC，培养48h后，收集各孔细胞，DTZ染色，计数。结果GH，HGF和NIC均起主要作用，HGF和NIC的交互作用不可忽视，最佳的生长因子组合及适配浓度为GH(100ng／ml)HGF(25ng／ml)NIC(100mmol／L)。结论GH，HGF和NIC均能促进体外培养的胰岛细胞的增殖，且组合GH(100ng／ml)HGF(25ng／ml)NIC(100mmol／L)的作用最大。     

肝切除技术的研究进展

肝切除技术已成为治疗各种肝脏良性、恶性肿瘤的最主要方法。文中主要从肝脏切除范围的界定、断肝新技术及腹腔镜肝切除技术这三方面的进展进行综述,从而提高对如何更加完善肝预切除方案和肝脏外科微创化肝脏外科领域里两大研究热点的认识。     

Fat-Derived Hormone Adiponectin Combined with FTY720 Significantly Improves Small-for-Size Fatty Liver Graft Survival

Owing to the discrepancy between organ donation and the demand for liver transplantation, expanding the liver donor pool is of vital importance. However, marginal liver grafts, such as small-for-size and/or fatty grafts, were associated with primary graft nonfunction or poor function. Therefore, novel combination therapies to rescue small-for-size fatty liver grafts should be investigated. In this study, we applied a combination therapy using a fat-derived hormone adiponectin (anti-steatosis) plus immunomodulator FTY720 (anti-inflammatory) in a rat liver transplantation model using small-for-size fatty liver grafts, and investigated the underlying protective mechanism such as anti-steatosis, intra-graft energy metabolism, hepatic microcirculatory changes, cell signaling cascades for survival, apoptosis and inflammation. The current study demonstrated that even a single treatment of adiponectin or FTY720 improved the 7-day graft survival from 0% to 62.5% (p = 0.001). The combination therapy significantly increased the 7-day graft survival rate to 100% by remarkable attenuation of graft steatosis and acute phase inflammatory response, significant activation of cell survival Akt pathway and maintenance of intra-graft adenosine triphosphate metabolism and improvement of hepatic microcirculation. In conclusion, the fat-derived hormone adiponectin combined with FTY720 might be a novel combination drug therapy for prevention of small-for-size fatty liver graft injury.     

Liver regeneration in acute severe liver impairment: a clinicopathological correlation study.

BACKGROUND: Although normally quiescent, the adult mammalian liver possesses a great capacity to regenerate after different types of injury. Major players in the regeneration process are mature residual cells, including hepatocytes, cholangiocytes and stromal cells. However, if the regenerative capacity of mature cells is impaired, hepatic progenitor cells (HPCs) are activated and expand into the liver parenchyma. Upon transit amplification, the progenitor cells generate new hepatocytes and biliary cells to restore liver homeostasis. AIMS/METHODS: To study the relationship between different histopathological parameters as well as their correlations with clinical parameters and outcome, we examined liver specimens from 74 patients with acute or subacute severe liver impairment by immunohistochemistry for CK7/CK19 (evaluation of HPCs activation/differentiation), Mib1(Ki 67)/P21 (evaluation of proliferative activity/proliferation arrest of hepatocytes) and hematoxylin and eosin (evaluation of hepatocyte loss). RESULTS: Of the 74 patients, 32% survived without transplantation, 14% died without transplantation and 54% were transplanted. Our results show that a threshold of 50% loss of hepatocytes, associated with significant decrease in the proliferative activity of remaining mature hepatocytes, is needed for extensive hepatic progenitor cell activation. Such activation is a sign of disease severity and occurs early (within 1 week) in the disease course. However, development of intermediate hepatocytes, suggesting HPCs differentiation towards mature hepatocytes, takes at least 1 week's time. We found a positive correlation between histopathological parameters (percentage hepatocyte loss, number of proliferating hepatocytes and number of HPCs) and clinical parameters of liver impairment such as model for end stage liver diseases (MELD). Surviving patients compared with those who either died or were transplanted had significantly less hepatocyte loss, less HPCs activation and more mature hepatocyte proliferative activity. Hepatocyte proliferative activity and degree of hepatocyte loss were the most important independent histopathological parameters in predicting outcome. CONCLUSION: Liver biopsy can provide important additional information in a patient with severe acute liver impairment.     

Incretin mimetics as a novel therapeutic option for hepatic steatosis.

BACKGROUND: Fat accumulation in the liver or non-alcoholic fatty liver disease (NAFLD) is regarded as a key pathogenic factor and component of the metabolic syndrome. It was reported that administration of the incretin mimetic exenatide reversed hepatic steatosis in an obese mouse model. We had the opportunity to study the effect of additional exenatide administration on liver fat content in a patient with type 2 diabetes. CASE REPORT: A 59-year-old male with poorly controlled type 2 diabetes was treated with exenatide in addition to metformin monotherapy. Following 44 weeks of exenatide therapy, mean the liver fat measured by liver spectroscopy declined from 15.8% to 4.3%. This dramatic decrease in liver fat was accompanied by significant beneficial changes in several cardiovascular disease risk factors and improvement of all liver enzymes, in particular alanine aminotransferase, the most important marker of liver steatosis. CONCLUSION: This case report suggests that the incretin mimetic exenatide decreases hepatic fat accumulation and may play a role in the future treatment of NAFLD, and the associated insulin resistance and cardiovascular risk factors in an ever-growing high-risk population.     

肝动脉结扎在重度肝外伤中的临床应用

目的探讨严重肝外伤的治疗和疗效。方法总结分析10年间收治的81例严重肝外伤,按AAST分级法。Ⅲ级30例,Ⅳ级36例,Ⅴ级15例,分别以不同的方法治疗对比。结果治愈71例,10例死于术后胆瘘并发感染及多器官衰竭,为能忽视Ⅲ级肝外的肝动脉结扎及T管引流术。结论肝动脉结扎加网膜及纱布带填塞、不规则的肝叶切除、T管引流、肝血回输,是提高严重肝外伤抢救成功率的重要措施。     

影响肝外伤手术死亡的危险因素分析

目的分析影响肝外伤手术死亡的危险因素,探讨其临床意义。方法根据AAST和ISS标准,回顾性分析90例肝外伤手术病例,对影响手术死亡的危险因素进行单因素比较和Logistic回归分析。结果死亡15例,其中Ⅲ级2例、Ⅳ级4例、Ⅴ级9例,总体手术死亡率17%。Ⅳ~Ⅴ级肝外伤手术方式的单因素比较提示:清创性肝切除术的相对危险度是0.73;而规则性肝切除术、肝静脉或肝后下腔静脉修补术相对危险度分别是1.32、1.52。Logistic回归分析提示:ISS分会和术中失血量是影响手术死亡率的2个独立因素。结论ISS分值、术中失出血量和手术方式是影响肝外伤手术死亡的3个重要因素,娴熟的手术技能和合理的手术方式可以减少术中出血量和降低手术死亡率。     

胃癌根治术中肝动脉变异及意义

目的介绍胃癌根治术时发现肝动脉变异情况。方法回顾性分析208例胃癌根治术时遭遇的肝动脉变异情况。结果208例中发现肝动脉变异3例,术中游离时注意保留肝脏、胆囊的血供分支。结论胃癌根治术时应注意肝动脉变异可能,避免损伤邻近器官的血供。     

无创伤法联合测定门静脉压力及肝血流评价肝硬化疗效

目的　为临床评价肝硬化疗效提供有价值的手段。方法　采用99Tcm-RBC及99Tcm-MIBI分别测定 16例肝硬化患者治疗前后的肝血流及门静脉压力。前者选择峰时 (T(max) 、半廊清时 (T1/ 2 )、廊清率 (K值 )及肝血流(LBF)等作为观察指标 ;后者以心 /肝 (H/L)比值及门静脉压力 (PVP)为观察指标。结果　治疗前Tmax、T1/ 2 、K值及LBF分别为 1.83± 1.0 4min、5 .3 7± 2 .19min、0 .10± 0 .0 3及 0 .45± 0 .16L/min ,而治疗后分别为 0 .86± 0 .2 0min、3 .80± 1.86min、0 .14± 0 .0 4及 0 .64± 0 .2 0L/min ,治疗前后各项指标均有非常显著性差异 (P <0 .0 1或 0 .0 0 1)。服药前H/L、PVP分别为 0 .73± 0 .16及 3 .0 0± 0 .5 5kPa;治疗后分别为 0 .47± 0 .18及 2 .2 0± 0 .62kPa,与治疗前相比均有非常显著性差异 (均P <0 .0 0 1)。结论　所用测定肝血流及门静脉压力的两种方法均无创伤性 ,用于观察肝硬化疗效有一定价值     

生长激素抗肝纤维化的作用及其机制

目的　探讨重组人生长激素 (rhGH)对肝硬化大鼠在肝功能、门静脉高压等方面的治疗作用及其可能的机制。方法　雄性SD大鼠建立肝硬化模型 ,随机分组 ,分别给予NS、rhGH (333ng/KgBW ,ip ,qd× 7d)处理。 结果　rhGH处理前后肝硬化肝组织GHR的配体结合容量 [fmol/mg ,(31± 4 )vs .(4 0± 7) ]及其mRNA量 (iOD ,pixel)均显著升高 (2 3± 3)vs.(4 2± 8) ;P <0 0 5 ,肝硬化大鼠血清白蛋白 (g/L )显著升高 (2 9± 4 )vs .(37± 7) ;P <0 0 5、ALT活性 (U/L)显著降低 (89± 15 ,6 9± 7;P <0 0 5 ) ,肝硬化肝组织丙二醛含量 (nmol/mg)显著降低 (18 7± 3 2 ,12 0± 2 2 ;P <0 0 5 )、超氧化物歧化酶活性 (U/mg)显著升高 (82 4± 10 8,10 2 9± 76 ;P <0 0 5 )、胶原纤维相对含量 (% )显著降低 (2 2 30± 3 86vs.14 70± 2 0 7;P <0 0 5 ) ,肝硬化大鼠的门静脉压 (cmH2 O)亦显著降低 (14 4± 2 0vs.9 3± 1 5 ;P <0 0 5 )。结论　药理剂量的rhGH能够促进肝硬化大鼠的白蛋白合成、改善肝细胞功能 ,有助于抑制肝组织纤维化、缓解门静脉压力。