甘草次酸靶向肝星状细胞治疗肝纤维化的初步研究

肝星状细胞(HSC)是肝纤维化发生和发展的主要细胞，将药物选择性地释投到HSC可以提高抗肝纤维化作用，减少不良作用。研究以6磷酸甘露糖(M6P)修饰的白蛋白(M6P-HSA)为载体，甘草次酸(G)靶向HSC治疗肝纤维化的可行性。     

肝星状细胞与炎症的关系

肝星状细胞(hepatic stellate cell,HSC)与肝纤维化形成密切相关,使得HSC被广泛地关注,肝纤维化是慢性肝病共有的病理改变,是肝脏对慢性损伤的一种修复反应,其特征为细胞外基质(extracellular matrix,EMC)的过度表达和异常沉积。活化的HSC是肝纤维化发生中EMC的主要来源,是肝纤     

肝星状细胞及相关细胞因子在肝纤维化形成中的作用

肝纤维化(hepatic fibrosis)是指肝脏内弥漫性细胞外基质(extracellular matrix,ECM)过度沉积的病理过程.肝星状细胞(hepatic stellate cells,HSC)被认为是ECM的主要来源细胞,在肝纤维化发生发展中起着关键作用.另外,各种病因引起肝细胞损伤时,Kupffers细胞(KF),肝窦内皮细胞等分泌一系列细胞因子,通过旁分泌和自分泌方式作用于邻近的HSC,影响其增殖,趋化和ECM代谢.因此,HSC及细胞因子与肝纤维化的发生发展关系极为密切,阐明其关系,有助于以HSC为靶点的肝纤维化方面的研究,现就其关系分别综述如下.     

肝星状细胞与肝纤维化

肝纤维化是各种慢性肝病共有的病理改变,逆转肝纤维化可阻止大多数慢性肝病进展。肝星状细胞(HSC)是肝内一种具有多功能、变化不定的非实质细胞,HSC活化是肝纤维化发生的中心环节。阐明其关系,有助于以HSC为靶点的肝纤维化方面的研究。     

肝星状细胞与肝纤维化研究进展

肝星状细胞(HSC)是肝脏的一种非实质细胞,HSC活化导致细胞外基质(ECM)的增加是肝纤维化形成并最终导致肝硬化、肝功能衰竭的主要原因.因此,加强对HSC激活与凋亡调控机制的研究,有助于我们对肝纤维化发生的本质的认识,从而能更有效地防治肝纤维化.     

硫氧还蛋白与肝纤维化相关研究进展

<正>肝纤维化是由各种原因引起慢性肝损伤的病理变化。它的特点是肝脏中细胞外基质(ECM)的过度积累,影响肝脏功能。肝纤维化的病因十分复杂,多种类型的慢性肝病均可以发展为肝纤维化。有关肝纤维化发病机制的研究主要集中在肝脏的炎症反应,氧化应激,肝细胞的生长和凋亡,以及肝星状细胞(HSC)的激活方面。硫氧还蛋白(Trx)是一种广泛存在于原核生物和真核生物体内的具有多种生物学功能的小分子量蛋     

TGF-β1在肝纤维化研究中的新进展

转化生长因子-β(transforming growth factoro-β,TGF-β1)是肝纤维化最关键的细胞因子,他与肝纤维化发生发展、细胞外基质(extracellularmatrix,ECM)代谢关系最为密切.学者们在肝纤维化疾病的大量研究中证明了TGF-β1在肝纤维化形成、发生及发展中有着重要的作用,而且近年来提出了针对干预TGF-β1的抗肝纤维化治疗新途径,在基因治疗及免疫治疗的研究方面取得可喜的进展.本文简要总结了国内外学者关于肝纤维化中TGF-β1的作用及以其为靶点的药物开发新进展.     

肝内肌成纤维细胞和星状细胞在肝纤维化中的作用

肝纤维化是不同病因长期作用于肝脏所致损伤后修复反应,发病机制主要是肝内纤维生成,细胞活化、增殖,合成大量细胞外基质(extracellur matrix.ECM),并伴有ECM降解不足,最终导致其在肝内大量积聚.近来有研究提示除肝星状细胞(hepatic satellite cell,HSC)外,肌成纤维细胞(myofibroblast,MF)可能是另一类参与肝纤维化进程并发挥重要作用的细胞,进一步确证上述研究结果将助于针对不同类型肝纤维化寻找和采取不同的干预方法,以更有效地阻断肝纤维化的进展.     

抗肝纤维化药物治疗的研究进展

肝纤维化是肝脏受到慢性损伤的一种修复反应,是多种慢性肝病共有的病理改变,可最终导致肝硬化、肝癌。肝纤维化的主要机制是以胶原为主的细胞外基质合成大于降解,从而使细胞外基质在肝脏过度沉积。目前认为,早期肝纤维化是一种可逆性病变,有效控制肝脏基础疾病或抗肝纤维化治疗对肝纤维化的治疗有重要意义。目前,药物治疗是抗肝纤维化治疗的主要方法,抗肝纤维化的药物治疗主要针对控制原发病、保护肝细胞、抑制肝星状细胞活化和增殖、抑制胶原合成、促进胶原降解及调控与纤维化有关的细胞因子、支持对症治疗等方面。本文将近年来肝纤维化药物治疗的研究进展进行综述。     

特异性靶向肝星状细胞治疗肝纤维化研究进展

肝纤维化是慢性肝病进展过程必经的一种病理组织学改变,而肝星状细胞的激活和增生是肝纤维化发生进展的中心环节.目前研究通过基因调控治疗及受体介导药物靶向肝星状细胞,可提高肝纤维化治疗的特异性,为临床应用开辟了新方向.     

Results of liver resection for primary liver cancer

At the Zhong Shan Hospital, Shanghai Medical University, between 1960 and 1991, liver resection was performed in 896 patients with primary liver cancer; local resection was performed in 552 patients (61.6%), left lateral segmentectomy in 114 (12.7%), left hemihepatectomy in 157 (17.5%), extended left hemihepatectomy in 19 (2.1%), right hemihepatectomy in 50 (5.6%), and extended right hemihepatectomy in 4 (0.4%). The overall operative mortality was 4.6%, but it was 22.0% in 1960–1970, 7.0% in 1971–1980, and 2.8% in 1981–1991. Encouraging changes in the prognostic pattern were observed when comparing the data for 1960–1970 (n=59), 1971–1980 (n=115), and 1981–1991 (n=722): the 5-year survival rate was 14.0%, 36.0%, and 50.8%, respectively, and the 10-year survival rate was 12.3%, 25.5%, and 40.8%, respectively. Significant differences in survival patterns were noted when these were analyzed on the basis of tumor size (≤5 vs >5cm), curative resection, tumor number, tumor capsule, and tumor emboli in the portal vein. In the entire series, 135 patients have survived for more than 5 years after resection, and 40 patients for more than 10 years after resection. One patient has survived for 32 years and is still alive, free of disease. The approaches to decreasing operative mortality and prolonging survival rate are discussed.     

Implication of normal liver enzymes in liver disease

Summary.  Chronic liver disease is usually asymptomatic until its late stages and also significant hepatic necroinflammation and fibrosis may be present in persistently normal ALT levels HBV, HCV carriers or similarly, in patients with nonalcoholic fatty liver disease. Given the large number of persons in the general population which may harbor a clinically significant liver disease behind the screen of normal alanine aminotransferase, more attention should be devoted to future research for alternative noninvasive markers of liver damage.     

Recurrence of autoimmune liver diseases after liver transplantation

Liver transplantation(LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis(AIH) and primary biliary cirrhosis(PBC), but not for primary sclerosing cholangitis(PSC), has decreased over the years due to the availability of effective medical treatment. Autoimmune liver diseases have superior transplant outcomes than those of other etiologies. While AIH and PBC can recur after LT, recurrence is of limited clinical significance in most, but not all cases. Recurrent PSC, however, often progresses over years to a stage requiring re-transplantation. The exact incidence and the predisposing factors of disease recurrence remain debated. Better understanding of the pathogenesis and the risk factors of recurrent autoimmune liver diseases is required to develop preventive measures. In this review, we discuss the current knowledge of incidence, diagnosis, risk factors, clinical course, and treatment of recurrent autoimmune liver disease(AIH, PBC, PSC) following LT.     

Life support of artificial liver: development of a bioartificial liver to treat liver failure

In recent years there has been a particular focus on research regarding tissue engineering targeting the liver, especially in terms of what types of cells and extracellular matrices should be organized and in what type of environments to create an artificial liver, i.e., a life-saving organ. The ideal is to use healthy human liver cells as a source of cells for such research, but there is an extreme shortage of human-donor livers that can be used for cell isolation. Therefore, we are presently working on the differentiation of embryonic stem cells into liver cells as well as reversibly immortalized human liver cell lines that can be cultured in large quantities and at low cost. We are also working on the development of a bioartificial liver (BAL) using such cells as a source. Herein, we introduce our findings on the current status of BAL development.     

Pulmonary aspects of liver disease and liver transplantation

This article has summarized the liver-lung relationships from a clinical perspective. The physiology, biochemistry, and molecular biology that link the two organs are of great importance in that many disorders described affect young patients. Indeed, pulmonary abnormalities in patients with hepatic disorders are frequent, and both the pulmonary and hepatic problems may be reversible in the current era of organ transplantation.