乙醇对大鼠肝窦内皮细胞窗孔的影响

目的 研究慢性乙醇摄取对大鼠肝窦内皮细胞(LSEC)窗孔的影响。方法 用乙醇直接灌胃的方法建立大鼠酒精性肝病动物模型，并于开始灌胃4周末、8周末、12周末，以及停止灌酒后(用平衡饲料继续喂养)12周末，分别处死实验组及对照组动物，经心脏灌流后取肝脏组织行HE染色和透射电镜观察LSEC窗孔的动态变化。结果 正常的LSEC扁平，胞核及细胞器排列规则，远侧胞质呈薄片状，有许多窗孔，内皮下缺乏基底膜(BM)；乙醇喂养4周末，可见部分LSEC远侧胞窗孔数减少，但BM未形成；8周末，窗孔数明显减少或消失，内皮下开始有不完全的BM形成，同时有功能活跃的纤维母细胞形成；12周末进一步加重，甚至可见完整的BM形成，但这种改变也多限于单个或邻近的窦状隙内，极少有广泛的纤维化形成；停药12周末，失窗孔及内皮下BM形成明显减轻。结论 随着乙醇的慢性刺激LSEC的去窗孔化和BM的形成也逐渐发生，严重时可形成肝窦毛细血管化和肝纤维化；这种早期即有局限性的去窗孔化改变和毛细血管化的生成可能是形成酒精性周围型纤维化的基础；去除病因后这种肝纤维化是可逆的。     

肝窦内皮细胞损伤在大鼠肝纤维化形成中的作用

目的 研究肝窦内皮细胞损伤在二甲基亚硝胺大鼠肝纤维化形成中的作用。方法 采用二甲基亚硝胺(dimethylnitrosamine,DMN)4周12次腹腔注射制备大鼠肝纤维化模型,应用电镜技术、免疫组织化学及图像分析方法结合血清生化测定,24周动态观察肝纤维化形成过程中肝窦内皮细胞损伤及其表型的改变。结果 造模2d后肝结构未见明显改变,肝窦内皮细胞(sinusoidal endothelial cell,SEC)远侧胞浆窗孔数减少、造模1周SEC失窗孔更明显,肝组织内未见明显变性坏死及纤维间隔形成,造模4周时见肝组织内大片出血坏死,有大量假小叶形成,内皮下出现SEC窗孔减少。SEC失窗孔早于肝细胞发生较为严重的坏死、肝纤维化的形成以及肝窦内皮下基底膜的形成。造模4周HA(ng/ml)和肝羟脯氨酸(ug/g)平均含量分别为231.30±143.80和223.04±37.09,对照组分别为56.50±18.10和61.55±20.85,t值在3.14～8.28,P<0.05。结论 DMN引起大鼠肝窦内皮细胞损伤及其表型改变可能是其诱导肝纤维化重要的始动机制之一。     

肝窦毛细血管化的研究进展

肝窦是不连续毛细血管 ,为通透性最大的血窦之一 ,其内皮细胞扁而薄 ,上有发达的窗孔 ,且窗孔无隔膜 ,整个细胞呈筛型状态。透射电镜在正常肝窦内皮外看不到有基底膜存在 ,如用特殊方法可显示少量网状纤维或 型胶原 ( - C)。肝纤维化过程中肝窦内皮窗孔逐渐减少或消失 ,内皮下基底膜形成 ,类似于连续性毛细血管 ,此过程称为肝窦毛细血管化 ( sinusoid capillarizatin) ,是肝纤维化的重要病理过程 ,对肝细胞功能影响很大 ,不仅发生较早 ,与肝星状细胞 ( HSC)的活化及窦内皮细胞的表型转化直接相关 ,还参与促进形成门脉高压症。病理刺激持…     

家兔非酒精性脂肪肝肝纤维化形成中层粘连蛋白及透明质酸的变化

目的:研究非酒精性脂肪肝家兔肝纤维化形成过程中肝窦壁层粘连蛋白(LN)及透明质酸(HA)的变化.方法:用高脂饲料诱发脂肪肝的方法建立家兔非酒精性肝病动物模型,取肝组织用扫描电镜、特殊染色等进行病理组织形态学观察;免疫组化检测LN;放射免疫法测定血清HA,研究非酒精性脂肪肝家兔在肝纤维化形成过程中肝窦壁基底膜成分的动态变化.结果:肝窦毛细血管化,即窗孔消失、基底膜形成;肝窦壁LN表达(面积百分比)和血清HA含量(mg/L)均随着肝纤维化形成逐渐增加,在8 wk末阳性最强,均与对照组有显著性差异(LN:25.2±1.0 vs 5.1±0.7,P＜0.01;血清HA:1422.18±20.9 vs 1189.3±13.1,P＜0.01),停止造模后逐渐下降,但停药8 wk均强于正常组.结论:家兔肝纤维化形成过程中,肝窦壁功能性基底膜被破坏,发生肝窦毛细血管化.血清HA含量的变化与电镜下SEC去窗孔的改变,以及LN的变化相一致.     

层黏连蛋白及其整合素受体在肝窦毛细血管化时的协调表达

目的：探讨层黏连蛋白（LN）及其整合素受体在肝窦毛血管化时的协调表达。方法：皮下注射四氯化碳制备大鼠肝纤维化模型,取肝组织用扫描电镜、特殊染色等进行病理组织形态学观察;层黏连蛋白及其整合素受体α6斑点免疫印迹研究。结果：动态观察了肝纤维化的特征病理变化;肝窦毛细血管化,即窗孔消失,基底膜形成及表型改变。LN在肝纤维化各期窦周阳性着色面积分别为0、1．902％、6．02％、9．68％、14．14％,其差异有显著性（P＜0．001）;正常时α6在肝窦内皮细胞（SEC）上无表达,肝窦毛细血管化时SEC出现α6表达与LN在窦周沉积一致,α6在纤维化时组织中含量明显高于正常（P＜0．05）。结论：LN于肝纤维经时在肝组织中不断沉积,并沿肝窦壁形成基底膜,使肝窦毛细血管化,且SEC出现LN整合素受体的诱导表达。提示LN及其整合素受体的协调表达在肝窦毛细血管化及肝纤维化的发病机制中有着重要的作用。     

日本血吸虫感染BALB/c小鼠肝窦的动态观察

目的观察感染日本血吸虫BALB／c小鼠肝窦动态变化，及其与肝纤维化和肝细胞损伤的关系。方法建立感染日本血吸虫BALB／c小鼠肝纤维化动物模型，肝标本行常规病理染色和天狼猩红染色，进行肝纤维化程度的半定量分析，免疫组化染色检测肝窦Ⅳ型胶原（C—Ⅳ）和第Ⅶ因子相关抗原（vWF）的表达，测血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST），另每组取2只小鼠新鲜肝组织进行透射电镜观察。结果感染小鼠肝窦内皮细胞（SEC）第4周窗孔减少、变小，第8周窗孔消失及SEC下基底膜（BM）形成，肝窦C—Ⅳ和vWF随感染时间的延续表达逐渐增强，肝纤维化程度也逐渐增高，血清ALT和AST与感染时间无关。结论血吸虫感染所引起的小鼠SEC表型改变可能是其诱导肝纤维化的始动机制之一。     

肝窦毛细血管化在二甲基亚硝胺大鼠肝纤维化门静脉高压形成中的作用

目的 研究肝窦毛细血管化在二甲基亚硝胺(DMN)大鼠肝纤维化门静脉高压形成中的作用。方法经4周12次腹腔注射DMN制备火鼠肝纤维化模型,应用电镜技术、免疫组织化学方法结合大鼠门静脉压力测定,24周动态分析肝纤维化形成过程中肝窦毛细血管化与门静脉压力变化的相关性。结果 大鼠门静脉压力随着造模的进行不断升高,造模4周时达(1.10 ±0.18)kPa,明显高于对照组(0.52±0.04)kPa(t=6.41.P<0.0 1)。造模停止后,大鼠门静脉压力逐渐恢复正常。其动态变化与电镜下肝窦毛细血管化的变化规律一致;与反映肝窦内皮表型改变的第Ⅷ因子相关抗原的动态变化成正相关(r=0.833,P<0.01);与反映肝窦内皮下基底膜形成的层黏连蛋白的动态变化成正相关(r=0.953,P<0.01);与反映肝窦壁星状细胞活化收缩的α-平滑肌肌动蛋白的动态变化成正相关(r=0.919,P<0.01)。结论 肝窦毛细血管化是DMN肝纤维化模型门静脉高压产生的主要原因。     

肝窦内皮细胞与肝窦毛细血管化研究进展

肝窦内皮细胞具有开放的、没有横膈膜的窗孔,内皮下没有基底膜。这种结构有利于调控肝细胞与肝窦血液的物质交换。肝窦内皮细胞能分泌内皮素-1和一氧化氮,并通过窗孔的变化,对肝脏微循环进行调节,同时可分泌大量的形成基底膜的成分,在肝窦毛细血管化的过程中起主导作用。肝窦内皮细胞表型标志发生变化,Ⅷ因子相关抗原、CD44等表达增强,也是肝窦毛细血管化的重要标志。笔者对肝窦内皮细胞的结构及其在肝窦毛细血管化中的功能和表型变化进行综述。     

环氧合酶-2在四氯化碳诱导肝硬化大鼠肝窦毛细血管化形成中的作用

目的 观察环氧合酶-2(COX-2)在实验性肝硬化大鼠肝窦毛细血管化形成中的作用.方法 腹腔注射CCl4每周2次共8周诱导雄性SD大鼠肝硬化模型.将SD大鼠分成3组:正常对照组(n=10)、模型对照组(n=15)和罗非昔布治疗组(10 mg·kg-1·d-1,n=15).光镜下观察肝组织标本,电镜观察肝窦超微结构改变.用Western印迹和免疫组化法检测基底膜蛋白主要成分层粘连蛋白(LN)和Ⅳ型胶原,同时通过Ⅷ因子相关抗原(vWF)免疫组化标记微血管牛成密度.结果 与模型对照组相比,罗非昔布干预治疗能减少肝纤维化面积(分别为30.7±8.9和23.5±6.5,P<0.05).光镜及电镜提示,在模型对照组可见肝窦内皮细胞窗孔减少、缩小,有完整的基底膜形成,Disse腔隙内有大量的胶原纤维沉积,罗非昔布组上述病变有所减轻.随着肝硬化的形成,肝组织微血管密度明显升高,罗非昔布组肝组织微血管密度(6.4±0.7)较模型对照组(11.3±1.6)明显降低(P<0.01).肝硬化时肝组织表达Ⅳ型胶原和LN蛋白明显增加(分别为3.8±0.4和3.7±0.5),罗非昔布能降低Ⅳ犁胶原和LN的表达(分别为3.0±0.5和3.0±0.5;与模型对照组相比两者均为P相似文献   

晚期日本血吸虫病患者肝窦病变的观察

目的 观察晚期日本血吸虫病（晚血）患者肝窦病变，并探讨其与肝纤维化程度、肝功能的关系。方法 26例晚血患者肝活检标本和5例正常肝标本行常规病理染色和天狼猩红染色，进行肝纤维化程度的半定量分析；应用鼠抗人Ⅳ型胶原（C—IV）单克隆抗体和兔抗人层粘蛋白（LN）多克隆抗体进行免疫组织化学（免疫组化）染色，阳性者进行定量检测；放射免疫法检测血清透明质酸（HA），自动生化分析仪检测肝功能；对其中5例患者和2例正常肝标本进行透射电镜观察。结果 肝纤维化程度为Ⅰ级、Ⅱ级和Ⅲ级的患者分别为5、11和10例，晚血患者肝窦壁C-Ⅳ和LN表达增强，并与肝纤维化程度及部分肝功能指标水平相关（P＜0．05或P＜0．01），与血清HA水平无关（P〉0．05）。晚血患者肝窦内皮细胞（SEC）失窗孔及SEC下可见基底膜（BM）的形成，SEC胞浆内出现Weibel、Palade等发现的小体（简称WP小体），肝窦腔内有脱落的肝细胞微绒毛。结论晚血患者肝窦存在病变，与肝纤维化程度及肝功能改变有关。     

肝泰胶囊抗肝纤维化作用的实验研究

目的 探讨肝泰胶囊对CCl4诱导的肝纤维化大鼠的作用及其抗肝纤维化的可能机制。方法将40只Wistar大鼠随机分为正常对照组、肝纤维化模型组、肝泰组及肝复乐组。采用光镜、电镜观察肝组织病理学改变，VonGieson（VG）染色及胶原面积半定量分析反映各组肝纤维化程度。采用放射免疫法测定血清层粘连蛋白（LN）、Ⅲ型前胶原（PC-Ⅲ）、Ⅳ型前胶原（Ⅳ-C）、透明质酸（HA）的含量，同时用高效液相色谱-电化学（HPLC—ECD）法检测肝组织中去甲肾上腺素（Norepinephrine，NE）的水平。结果肝泰组较模型组比：①肝组织肝纤维化程度明显改善；②肝组织胶原纤维面积明显减少；③血清透明质酸和层粘连蛋白显著降低；④肝功能损伤明显减轻；⑤组织中NE的含量明显高于模型组。结论肝泰对慢性肝损伤有一定的保护作用。     

Hepatic microvascular features in experimental cirrhosis: a structural and morphometrical study in CCl4-treated rats

BACKGROUND/AIMS: In this study, a detailed morphometrical analysis of the hepatic microvasculature in the different zones of hepatic parenchyma was performed in normal and cirrhotic rat liver (CCl4-induced). The aims were to detect, in CCl4-induced cirrhosis, the real presence of the "capillarization" of hepatic sinusoids and to assess alterations of the sinusoid/parenchyma ratio within the nodule. METHODS: Cirrhosis was promoted by controlled intragastric CCl4 administration. Scanning electron microscopy of the vascular corrosion cast technique associated with light microscopy and transmission electron microscopy were used. RESULTS: Evidence of connective tissue in the space of Disse was found only in sinusoids located near portal tracts or large fibrotic areas, and this was also confirmed by laminin immunohistochemistry. In contrast, all the intranodular sinusoids lacked real basal membrane and connective fibers in the space of Disse and, displayed normal fenestrations. The parenchymal area, sinusoidal area, mean sinusoidal area, sinusoidal perimeter, hepatocyte area and the reciprocal ratios were all considered in the morphometrical analysis. The sinusoids were of uniform size in the periportal, periseptal and pericentral areas of the cirrhotic liver without the typical zonal differences of the normal liver. The areas occupied by sinusoids per unit of parenchyma and the sinusoid/hepatocyte interfaces disposable for metabolic exchanges were markedly smaller (p<0.01) in cirrhotic than normal liver. CONCLUSION: Our findings indicate that capillarization of hepatic sinusoids occurs only in very limited regions of the cirrhotic parenchyma, and thus this phenomenon does not have relevant functional consequences. Furthermore, the cirrhotic parenchyma appears not to be supplied by sinusoids and lacks features of zonation, which is a condition that could play a major role in the development and progression of liver failure.     

Pathological mechanisms of alcohol-induced hepatic portal hypertension in early stage fibrosis rat model

AIM: To study the role of hepatic sinusoidal capillarization and perisinusoidal fibrosis in rats with alcohol-induced portal hypertension and to discuss the pathological mechanisms of alcohol-induced hepatic portal hypertension. METHODS: Fifty SD rats were divided into control group (n=20) and model group (n=30). Alcoholic liver fibrosis rat model was induced by intragastric infusion of a mixture containing alcohol, corn oil and pyrazole (1 000:250:3). Fifteen rats in each group were killed at wk 16. The diameter and pressure of portal vein were measured. Plasma hyaluronic acid (HA), type Ⅳ collagen (CoⅣ) and laminin (LN) were determined by radioimmunoassay. Liver tissue was fixed in formalin (10%) and 6-μm thick sections were routinely stained with Mallory and Sirius Red. Liver tissue was treated with rabbit polyclonal antibody against LN and ColⅣ. Hepatic non-parenchymal cells were isolated, total protein was extracted and separated by SDS-PAGE. MMP-2 and TIMP-1 protein expression was estimated by Western blotting. RESULTS: The diameter (2.207 ± 0.096 vs 1.528±0.054mm, P<0.01) and pressure (11.014±0.395 vs 8.533±0.274 mmHg, P<0.01) of portal vein were significantly higher in model group than those in the control group. Plasma HA (129.97±16.10 vs 73.09±2.38 ng/mL, P<0.01), ColⅣ (210.49±4.36 vs 89.65±4.42 ng/mL, P<0.01) and LN (105.00±7.29 vs 55.70±4.32 ng/mL, P<0.01) were upregulated in model group. Abundant collagen deposited around the central vein of lobules, hepatic sinusoids and hepatocytes in model group. ColⅠ and ColⅢ increased remarkably and perisinusoids were almost surrounded by ColⅢ. Immunohistochemical staining showed that ColⅣ protein level (0.130±0.007 vs 0.032±0.004, P<0.01) and LN protein level (0.152±0.005 vs 0.029±0.005, P<0.01) were up-regulated remarkably in model group. MMP-2 protein expression (2.306±1.089 vs 0.612±0.081, P<0.01) and TIMP-1 protein expression (3.015±1.364 vs 0.446±0.009, P<0.01) in freshly isolated hepatic non-parenchymal cells were up-regulated in model group and TIMP-1 protein expression was evidently higher than MMP-2 protein expression (2.669±0.170 vs 1.695±0.008, P<0.05). CONCLUSION: Hepatic sinusoidal capillarization and peri-sinusoidal fibrosis are responsible for alcohol-induced portal hypertension in rats.     

Melatonin ameliorates experimental hepatic fibrosis induced by carbon tetrachloride in rats

AIM： To investigate the protective effects of melatonin on carbon tetrachloride （CCl4）-induced hepatic fibrosis in experimental rats.
METHODS： All rats were randomly divided into normal control group, model control group treated with CCl4 for 12 wk, CCl4 ＋ NAC group treated with CCl4 ＋ NAC （100 mg/kg, i.p.） for 12 wk, CCl4 ＋ MEL-1 group treated with CCl4 ＋ melatonin （2.5 mg/kg） for 12 wk, CCl4 ＋ MEL-2 group treated with CCl4 ＋ melatonin （5.0 mg/kg） for 12 wk, and CCl4 ＋ MEL-3 group treated with CCl4 ＋ melatonin （10 mg/kg）. Rats in the treatment groups were injected subcutaneously with sterile CCl4 （3 mL/kg, body weight） in a ratio of 2：3 with olive oil twice a week. Rats in normal control group received hypodermic injection of olive oil at the same dose and frequency as those in treatment groups. At the end of experiment, rats in each group were anesthetized and sacrificed. Hematoxylin and eosin （HE） staining and Van Gieson staining were used to examine changes in liver pathology. Serum activities of alanine aminotransferase （ALT）, aspartate aminotransferase （AST） and protein concentration weremeasured with routine laboratory methods using an autoanalyzer. Hydroxyproline （HYP） content in liver and malondialdehyde （MDA） and glutathione peroxidase （GPx） levels in liver homogenates were assayed by spectrophotometry. Serum hyaluronic acid （HA）, laminin （LN）, and procollagen Ⅲ N-terminal peptide （PⅢNP） were determined by radioimmunoassay.
RESULTS： Pathologic grading showed that the fibrogenesis was much less severe in CCl4 ＋ MEL3 group than in model control group （u = 2.172, P 〈 0.05）, indicating that melatonin （10 mg/kg） can significantly ameliorate CCl4-induced hepatic fibrotic changes. The serum levels of ALT and AST were markedly lower in CCl4 ＋ MEL treatment groups （5, 10 mg/kg） than in model control group （ALT： 286.23 ± 121.91 U/L vs 201.15 ± 101.16 U/L and 178.67 ± 103.14 U/L, P = 0.028, P = 0.007; AST： 431.00 ± 166.35 U/L vs 321.23 ± 162.48 U/L and 292.42 ± 126.23 U/L, P = 0.043, P = 0.013）. Similarly, the serum laminin （LN） and hyaluronic acid （HA） levels and hydroxyproline （HYP） contents in liver were significantly lower in CCl4 ＋ MEL-3 group （10 mg/kg） than in model control group （LN： 45.89 ± 11.71 μg/L vs 55.26 ± 12.30 μg/L, P = 0.012; HA： 135.71±76.03 μg/L vs 201.10 ± 68.46 μg/L, P = 0.020; HYP： 0.42 ± 0.08 mg/g tissue vs 0.51 ± 0.07 mg/g tissue, P = 0.012）. Moreover, treatment with melatonin （5, 10 mg/kg） significantly reduced the MDA content and increased the GPx activity in liver homogenates compared with model control group （MDA： 7.89 ± 1.49 noml/mg prot vs 6.29 ±1.42 noml/mg prot and 6.25 ±2.27 noml/mg prot, respectively, P = 0.015, P = 0.015; GPx： 49.13 ±8.72 U/mg prot vs 57.38 ±7.65 U/mg prot and 61.39 ±13.15 U/mg prot, respectively, P = 0.035, P = 0.003）.
CONCLUSION： Melatonin can ameliorate CCl4 -induced hepatic fibrosis in rats. The protective effect of melatonin on hepatic fibrosis may be related to its antioxidant activities,     

肝纤维化小鼠肝组织血管新生特点及其形成机制

目的 探讨肝纤维化小鼠肝组织血管新生特点及其形成机制.方法 C57BL/6小鼠随机分为正常对照组与模型18 h、4周、8周组,共4组.采用CCl4诱导小鼠肝纤维化模型.天狼猩红染色观察肝组织胶原沉积;免疫荧光检测肝组织vWF蛋白表达,分析微血管密度;扫描电镜及透射电镜观察肝窦内皮结构;Western blot法检测肝组...     

Effect of Danshao Huaxian capsule on expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in fibrotic liver of rats

AIM: To investigate the effects of Danshao Huaxian (DSHX) capsules, a preparation of traditional Chinese medicine, on the expression of matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the fibrous livers of rats. METHODS: Eighty male Wistar rats were randomly divided into normal control group (group A), CCl4-induced hepatic fibrosis group (group B), non-DSHX-treated group (group C), low dose-treated group (group D), and high dose-treated group (group E). Fibrous liver models in rats were induced by subcutaneous injection of CCl4, oral administration of alcohol and high-lipid/low-protein diet for 8 wk. After the models were established, the rats in groups D and E were orally given a low dose (0.5 g/kg) and a high dose (1.0 g/kg) of DSHX daily for 8 wk, respectively. Then, the liver indexes, serum hyaluronic acid (HA) and alanine aminotransferase (ALT) were examined. The degree of hepatic fibrosis was evaluated by optical microscopy. Hydroxyproline (Hyp) in the urine was determined, and the expression of MMP-1 and TIMP-1 was detected by immunohistochemical techniques. RESULTS: In groups D and E, the liver indexes, levels of serum HA and ALT reduced and development of hepatic fibrosis weakened significantly. The urinary Hyp and expression of MMP-1 in the liver tissues elevated, but the expression of TIMP-1 decreased obviously, as compared to groups B and C. CONCLUSION: DSHX enhances the expression of MMP-1 but decreases that of TIMP-1 in liver tissues of CCl4-induced hepatic fibrotic rats, which may result in its elevated activity that contributes to fighting against hepatic fibrosis.     

小鼠血吸虫病肝纤维化的超微结构动态观察

目的　研究血吸虫病小鼠肝纤维化过程中几种相关细胞和肝组织超微结构动态变化 ,以探讨血吸虫病肝纤维化的可能机制。　方法　日本血吸虫尾蚴经皮肤感染小鼠建立血吸虫病肝纤维化模型。常规方法制作肝组织透射电镜标本并观察。常规 HE染色观察其病理变化。　结果　 HE染色显示小鼠血吸虫病肝纤维化模型建立成功。电镜观察显示小鼠感染后 6 wk,急性肉芽肿周围的肝细胞发生坏死 ,肝窦内皮细胞窗孔减少 ,贮脂细胞 (FSC)脂滴减少 ,枯否细胞胞浆出现大吞噬体和粗面内质网。 8wk时部分肝细胞发生脂肪变性 ,少数肝细胞间隙增宽 ,间面出现微绒毛。肝窦周隙内充满大量胶原纤维 ,并形成肝窦毛细血管化。FSC胞浆出现含胶原原纤维的分泌泡 ,周围见大量胶原纤维。枯否细胞粗面内质网增加。 10 wk时 FSC转变为肌成纤维细胞。 12 wk时肌成纤维细胞减少 ,成纤维细胞和纤维细胞增加。　结论　 FSC被激活转化为肌成纤维细胞是血吸虫病肝纤维化发生的关键环节 ,激活的枯否细胞、损伤的肝细胞和肝窦内皮细胞与 FSC的活化密切相关 ,肝窦毛细血管化可能加速肝纤维化的发展。     

银杏叶提取物对肝硬化大鼠门静脉压及肝窦病理变化的影响

目的探讨银杏叶提取物（EGb）对肝硬化大鼠肝窦微循环及门静脉高压的影响。方法25只雄性Wistar大鼠分为3组：正常对照组（5只）,CCl_4组（10只）,EGb治疗组（10只）。肠系膜上静脉插管测定各组大鼠灌注EGb前后门静脉压力;肝组织匀浆中检测丙二醛（MDA）,血管内皮素（ET-1）,血小板活化因子（PAF）,一氧化氮（NO）,构生型一氧化氮合成酶（cNOS）和诱生型一氧化氮合成酶（iNOS）水平;电镜观察各组肝窦微循环特征。结果EGb灌注后CCl4组门静脉压由（8．7±0．8）mm Hg降至（7．4±0．6）mmHg,降低幅度15%,t 4．11,P＜0．01; EGb治疗组与CCl_4组比较,门静脉压、肝组织MDA、ET-1、PAF、NO和iNOS水平显著降低（P＜0．05或P＜0．01）,肝窦内胶原沉积、微血栓形成、肝窦毛细血管化程度减轻。结论银杏叶提取物能改善肝窦微循环障碍,降低门静脉压力,其可能机制是降低MDA、ET 1、PAF含量,下调iNOS的表达调节NO含量,对慢性肝病治疗具有重要意义。     

肝血窦内皮细胞在非酒精性脂肪性肝病发展中的作用

非酒精性脂肪性肝病(NAFLD)是以肝脏脂肪变、炎症和纤维化为主要表现的临床代谢综合征,日渐成为严重影响公众健康的常见慢性肝病。肝血窦内皮细胞(LSEC)是肝脏组织特化的血管内皮细胞,作为一道重要的血管屏障,其对肝脏细胞吸收和代谢源自肠道血液中的营养与物质成分发挥重要调节作用。介绍了NAFLD发生发展进程中LSEC毛细血管化、血管功能障碍及其参与调控肝脏炎症、血管生成、肝纤维化的研究进展。