肝窦内皮细胞在肝损伤中的功能研究进展

肝窦内皮细胞（liver sinusoidal endothelial cells, LSECs）位于肝血窦表面，是肝脏与血液接触的第一道防线，也是肝脏中含量最多的非实质细胞。在生理情况下，LSECs通过参与物质运输、代谢废物清除而诱导肝脏免疫耐受，从而维持肝脏稳态；在病理情况下，LSECs通过抗原递呈促进肝脏炎症反应。LSECs在维持肝再生和肝纤维化平衡中发挥了重要的调节作用。本文对LSECs功能、LSECs在肝损伤中的变化、调节LSECs功能相关的信号通路以及LSECs与肝内其他细胞的相互作用等四方面研究进展进行综述，从而进一步明确LSECs的功能及在肝损伤中的作用。     

肝窦内皮细胞在非酒精性脂肪性肝病中的研究进展

非酒精性脂肪肝性肝病(NAFLD)在世界范围内广泛流行, 是非常严重的公共卫生问题, 目前尚无有效的药物治疗措施。肝窦内皮细胞(LSECs)是肝脏中占比最大的非实质细胞, 但目前LSECs在NAFLD中发挥的作用尚不明确。现就近年LSECs在NAFLD中相关研究进展进行综述, 以期为后续的研究提供一定的参考。     

肝病中的肝细胞凋亡

细胞凋亡(apoptosis)是细胞生命的基本特征之一,加强其研究对于理解生命个体的正常发育、疾病过程及其影响因素等具有重要意义。现将肝病中的细胞凋亡研究进展综述如下。　　一、肝细胞凋亡与肝非实质细胞　　肝非实质细胞对维持肝细胞的生理功能起到重要作用。研究表明,这些非实质肝细胞与肝细胞凋亡有着重要关系。Bhathal等[1]在研究阻塞性黄疸时发现肝胆管内皮细胞过度增生,通过细胞凋亡的机制可缓解阻塞性黄疸病情。Braun等[2]报道肝部分切除术后,肝非实质细胞产生TGF-β来调控细胞凋亡以旁路途径来调控肝细胞增殖及肝脏再生。枯否细…     

肝窦内皮细胞研究进展

肝窦内皮细胞(sinusoidal endothelial cell,SEC)是数量最多的肝脏非实质细胞,占非实质细胞总数的44％～60％,其形态结构和功能具有异质性。SEC与肝微循环、血脂代谢、内分泌代谢、内环境稳定、肝再生、肝细胞移植和肝癌发生等密切相关。     

肝窦内皮细胞研究进展

肝窦内皮细胞（sinusoidal endothelical cell,SEC)是数量最多的肝脏非实质细胞，占非实质细胞总数的44％－60％，其形态结构和功能具有异质性。SEC与肝微循环、血脂代谢、内分泌代谢、内环境稳定、肝再生、肝细胞移植和肝癌发生等密切相关。     

肝血窦内皮细胞在肝再生和肝纤维化发生中的作用

肝血窦内皮细胞是肝脏非实质细胞的主要组成细胞,是覆盖于肝窦的薄层扁平状细胞,表面富含窗孔,是肝窦和窦状间隙之间溶质交换的开放通道。肝血窦内皮细胞的分泌功能尤其是Wnt信号通路在维持Axin2+源性肝细胞的自我更新、促进肝部分切除或肝损伤时肝再生中均发挥重要的保护作用。肝损伤时,肝血窦内皮细胞结构发生改变,表现为窗孔消失和内皮下基底膜的形成,即肝窦毛细血管化。肝窦毛细血管化既是肝纤维化发生的前奏,也会促进肝纤维化的进展。肝窦内皮细胞在不同生理或病理状态下可通过信号通路的转换实现肝再生和肝纤维化调控作用的转换。肝血窦内皮细胞参与肝再生和肝纤维化机制的深入认识有望为慢性肝病的防治提供新的治疗靶点。     

肝窦内皮细胞与非酒精性脂肪性肝病的研究进展

非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是一个与代谢综合征相关的日益扩大的健康问题.肝窦内皮细胞(liver sinusoidal endothelial cells,LSECs)是位于血液与其他肝细胞类型之间高度专业化的内皮细胞,由窗孔组成,具有高内吞能力,并在维持肝脏整体稳态中发挥重要作用.病理条件下LSECs可能是多种慢性肝病的关键事件.本篇综述介绍了LSECs的独特生理结构和功能,重点总结了NAFLD中LSECs的主要变化(包括肝窦毛细血管化、血管生成、血管收缩、促炎和促纤维化)及其发生机制,还涉及LSECs对NAFLD进展的影响,旨在说明LSECs靶向治疗对NAFLD具有潜在疗效.     

肝内四种非实质细胞的功能

肝内四种非实质细胞中，肝窦内皮细胞有高度通透性能，所含筛板样小孔可允许小分子物质进入窦周间隙，其清除受体又可清除废物。枯否细胞为定居于肝脏的巨噬细胞，有清除内毒素、细菌、病毒和瘤细胞的功能，参与防御机制。星状细胞贮存维生素Ａ，合成细胞外基质，在肝纤维化中具有重要性，又是肝再生时细胞因子的来源，此外它还有调节肝窦血流的作用。小窝细胞为自然杀伤细胞，对瘤细胞有细胞毒作用     

肝窦内皮细胞调控肝脏微环境影响肝纤维化的研究进展

肝窦内皮细胞不仅是血液和肝细胞进行物质交换的重要中介细胞,也是慢性肝损伤因素导致肝纤维化和肝硬化的重要肝非实质细胞。它主要通过与肝星状细胞、肝细胞、Kupffer细胞的相互作用和介导肝脏硬度、肝脏血管再生从而调控肝脏微循环,参与肝纤维化的发展。阐明这些机制,有助于探索肝纤维化治疗的新靶点和方案。     

大鼠肝窦内皮细胞的分离、培养及鉴定

肝脏是由实质细胞和非实质细胞组成的具有复杂功能的器官，其中肝窦内皮细胞(sinusoidal endothelial cells，SEC)占肝非实质细胞的40％，在肝窦内形成一连续的带窗孔结构的衬垫细胞层，是肝内物质交换的屏障。与普通血管内皮细胞相比，SEC具有特殊的表面标志、结构和功能，在肝脏的生理、病理及器官移植过程中具有重要作用。但由于SEC的原代分离培养十分困难，因此阻碍了对其功能的深入研究。本研究旨在建立大鼠SEC的分离、培养及鉴定方法，为其生物学特性及功能的研究奠定基础。     

肝移植大鼠肝窦内皮细胞细胞凋亡与移植肝肝细胞损害的关系

目的探讨冷保存肝移植大鼠肝窦内皮细胞（SEC）细胞凋亡与移植肝肝细胞损害的关系。方法雄性SD大鼠随机分为假手术组（n=6）、UW1h肝移植组（11=48）、UW12h肝移植组（n=48）。参照Kamada的方法行原位肝移植（OLT）。观察大鼠I68h存活率。分别于术后不同时相点采取血液及组织标本，检测血清丙氨酸氨基转移酶（ALT）及透明质酸（HA）水平；TUNEL法检测SEC凋亡，透射电镜观察细胞凋亡的形态学改变。结果UW12h组168h存活率为50％，显著低于UW1h组（F=6．39，P〈0．05）。UW12h组肝移植后血清ALT、HA水平明显高于UW1h组（F=3．99，P〈0．05；F=12．43，P〈0．05），两组大鼠ALT水平均于术后6h达高峰。UW12h组SEC凋亡指数（AI）明显高于UW1h组和假手术组（F值分别为63．58和86．58，P值均〈0．01），两组大鼠SEC的AI也于术后6h达高峰，与血中丙氨酸氨基转移酶（ALT）的高峰时相点一致。且两组大鼠SEC的AI均与ALT水平呈显著正相关（，值分别为1．0和0．962，P〈0．05）。结论SEC凋亡程度与移植肝肝细胞损害呈显著正相关，SEC凋亡是冷保存再灌注损伤的关锋环节。     

Structural and functional aspects of the liver and liver sinusoidal cells in relation to colon carcinoma metastasis

Nowadays, liver metastasis remains difficult to cure. When tumor cells escape and arrive in the liver sinusoids, they encounter the local defense mechanism specific to the liver. The sinusoidal cells have been widely described in physiologic conditions and in relation to metastasis during the past 30 years. This paper provides an "overview" of how these cells function in health and in diseases such as liver metastasis.     

Neuropilin-1: A feasible link between liver pathologies and COVID-19

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a tremendous impact on the health of millions of people worldwide. Unfortunately, those suffering from previous pathological conditions are more vulnerable and tend to develop more severe disease upon infection with the new SARS-CoV-2. This coronavirus interacts with the angiotensin-converting enzyme 2 receptor to invade the cells. Recently, another receptor, neuropilin-1 (NRP-1), has been reported to amplify the viral infection. Interestingly, NRP-1 is expressed in nonparenchymal liver cells and is related to and upregulated in a wide variety of liver-related pathologies. It has been observed that SARS-CoV-2 infection promotes liver injury through several pathways that may be influenced by the previous pathological status of the patient and liver expression of NRP-1. Moreover, coronavirus disease 2019 causes an inflammatory cascade called cytokine storm in patients with severe disease. This cytokine storm may influence liver sinusoidal-cell phenotype, facilitating viral invasion. In this review, the shreds of evidence linking NRP-1 with liver pathologies such as hepatocellular carcinoma, liver fibrosis, nonalcoholic fatty liver disease and inflammatory disorders are discussed in the context of SARS-CoV-2 infection. In addition, the involvement of the infection-related cytokine storm in NRP-1 overexpression and the subsequent increased risk of SARS-CoV-2 infection are also analyzed. This review aims to shed some light on the involvement of liver NRP-1 during SARS-CoV-2 infection and emphasizes the possible involvement this receptor with the observed liver damage.     

U94 of human herpesvirus 6 inhibits in vitro angiogenesis and lymphangiogenesis

Human herpesvirus 6 (HHV-6) is a lymphotropic virus, but recent observations showed that also vascular endothelial cells (ECs) are susceptible to infection, both in vivo and in vitro. The observation that lymph nodes are a site of viral persistence suggests that lymphatic ECs (LECs) might be even more relevant for HHV-6 biology than vascular ECs. Here, we provide evidence that HHV-6 can infect LECs in vitro and establish a latent infection. Thus HHV-6 infection induces the loss of angiogenic properties both in LECs and in vascular ECs, as shown by the inability to form capillary-like structures and to seal wound scratches. The antiangiogenic effects observed in infected cells are associated to the expression of HHV-6 U94/rep, a latency-associated gene. In fact, transfection of U94/rep or addition of recombinant U94/REP protein to ECs inhibits the formation of in vitro capillary-like structures, reduces migration of ECs, and blocks angiogenesis, rendering rat aortic rings insensitive to VEGF-induced vasculogenetic activity. The ability of U94/rep to block different angiogenetic steps may lead to approaches in the potential control of the proliferation of blood and lymphatic vessels.     

人肝窦内皮细胞中α1肾上腺素能受体亚型表达的初步实验研究

目的探究α₁肾上腺素能受体（α₁AR）各亚型在肝窦内皮细胞（LSEC）中的表达情况。 方法体外培养人原代LSEC，蛋白质印迹法验证α₁AR激动剂去氧肾上腺素和α₁AR阻滞剂多沙唑嗪对LSEC表达血管生成相关指标CD31和vWF的影响，并验证LSEC中α₁AR各亚型的表达情况。免疫组化染色验证小鼠肝脏α₁AR各亚型的表达情况。 结果α₁AR激动剂去氧肾上腺素可增加LSEC中CD31和vWF的表达，而α₁AR阻滞剂多沙唑嗪可拮抗此作用。体内和体外实验均在LSEC中检测到α_1aAR与α_1bAR的表达，未检测到α_1dAR的表达。 结论α₁AR参与LSEC表型的调控，且通过α_1aAR与α_1bAR两亚型实现此功能，因此α₁AR可能成为肝纤维化新的调控靶点。     

Endothelial GATA4 controls liver fibrosis and regeneration by preventing a pathogenic switch in angiocrine signaling

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Transplanted human bone marrow contributes to vascular endothelium

Recent evidence indicates that bone marrow is a source of endothelial progenitor cells that are mobilized into the peripheral blood in response to cytokines or tissue injury. Previously, we showed that functional endothelial cells (ECs) can be clonally derived from phenotypically defined hematopoietic stem cells. To determine the EC potential of human bone marrow and peripheral blood stem cells, blood vessels in sex-mismatched transplant recipients were evaluated. EC outcomes were identified by using a combination of immunohistochemistry and XY interphase FISH. Donor-derived ECs were detected in the skin and gut of transplant recipients with a mean frequency of 2% and could readily be distinguished from CD45-expressing hematopoietic stem cells. None of the >4,000 ECs examined had more than two sex chromosomes, consistent with an absence of cell fusion. Y chromosome signals were not detected in sex-matched female recipients, excluding the vertical transmission of male cells. None of the recipients evaluated before hematopoietic engraftment demonstrated donor-derived ECs, indicating a close linkage between the recovery of hematopoiesis and EC outcomes. Transplantable bone marrow-derived endothelial progenitor cells may represent novel therapeutic targets for hematopoietic and vascular disease.     

Age-related changes in the hepatic microcirculation in mice

Aging of the liver is associated with impaired metabolism of drugs, adverse drug interactions, and susceptibility to toxins. Since reduced hepatic blood flow is suspected to contribute this impairment, we examined age-related alterations in hepatic microcirculation. Livers of C57Bl/6 mice were examined at 0.8 (pre-pubertal), 3 (young adult), 14 (middle-aged), and 27 (senescent) months of age using in vivo and electron microscopic methods. The results demonstrated a 14% reduction in the numbers of perfused sinusoids between 0.8 and 27 month mice associated with 35% reduction in sinusoidal blood flow. This was accompanied by an inflammatory response evidenced by a fivefold increase in leukocyte adhesion in 27 month mice, up-regulated expression of ICAM-1, and increases in intrahepatic macrophages. Sinusoidal diameter decreased 6-10%. Liver sinusoidal endothelial cell (LSEC) dysfunction was seen as early as 14 months when there was a threefold increase in the numbers of swollen LSEC. The endocytotic capacity of LSEC also was found to be reduced in older animals. The sinusoidal endothelium in 27 month old mice exhibited pseudocapillarization. In conclusion, the results suggest that leukocyte accumulation in the sinusoids and narrowing of sinusoidal lumens due to pseudocapillarization and dysfunction of LSEC reduce sinusoidal blood flow in aged livers.