修回日期: 2006-05-20
接受日期: 2006-06-05
在线出版日期: 2006-08-28
目的: 研讨中药调肝理脾方和东宝肝泰片对乙醇性肝病肝纤维化的治疗效果.
方法: ♂SD大鼠经过9 wk乙醇混合物灌胃后, 模型组被处死, 取得肝脏, 其他动物随机分成自然恢复组(11 wk)、东宝肝泰片组和调肝理脾方组, 给予连续10 d的灌胃治疗, 然后处死并取得肝脏, 采用光镜、电镜观察肝细胞、肝星状细胞、肝窦内皮细胞、肝窦和窦周病理变化, 并以免疫组化方法观察3种细胞外基质分子变化.
结果: 模型组动物肝细胞混浊肿胀, 脂肪变性, 间质细胞增生, 细胞核深染, Masson染色并可见肝细胞周围铁丝网格样纤维化和中央静脉基底膜增厚; 自然恢复组肝细胞病变有所好转, 纤维化也有好转, 调肝理脾方组好转最明显. 电镜下显示, 模型组肝窦基底膜增厚, 窦周胶原原纤维大量增生, 肝细胞微绒毛大量减少、倒伏, 自然恢复组无明显好转, 调肝理脾方和东宝肝泰片片组有好转.Ⅰ型胶原和层黏蛋白恢复结果以调肝理脾方组最好, Ⅳ型胶原恢复结果以东宝肝泰片组最好.
结论: 调肝理脾方对病理性堆积的Ⅰ型胶原和层黏蛋白代谢有明显促进作用, 效果强于东宝肝泰片, 而且也能促进过多的Ⅳ型胶原恢复正常, 而东宝肝泰片在促进堆积的Ⅳ型胶原恢复方面强于调肝理脾方.
引文著录: 徐光福, 褚月虎, 王晓阳, 田德禄, 王新月, 李澎涛, 杨晋翔, 姜良铎. 中药调肝理脾方对大鼠乙醇性肝病肝纤维化的影响. 世界华人消化杂志 2006; 14(24): 2386-2394
Revised: May 20, 2006
Accepted: June 5, 2006
Published online: August 28, 2006
AIM: To investigate the effects of Tiangan Lipi decoction (TLD) and Dongbao Gantai tablets (DGT) on the alcoholic liver diseases in rats.
METHODS: The male SD rats in model group were decollated and the livers were harvested after being fed with a mixture of alcohol for 63 d, and the others were randomly divided into natural recovery (NR) group (11 wk), TLD treatment group and DGT treatment group. After lavage treatment for 10 d, all the rats were executed and livers were harvested for observation of pathological changes of hepatocytes, hepatic stellate cells, sinusoidal endothelial cells, sinus, and peri-sinus, respectively, under light and electron microscope, and three kinds of extracellular matrix (ECM) generation were also detected by immunohistochemistry.
RESULTS: The hepatocytes were tumid and turbid, with fatty denaturalization, and the hyperplasia of stromal cells appeared in model rats. Wire netting around hepatocytes and the incrassation of basilar membrane of central vein were clearly observed by Masson staining. The pathological changes, such as fibrosis, in NR group alleviated to some extent, and the changes recovered the most in TLD group. The incrassation of basilar membrane of sinus, with a great amount of fibril around, were found in model rats by electron microscopy. Microvilli of hepatocytes disappeared or fell down in large numbers, but changes of microstructures were markedly mitigated in DGT and TLD group in comparison with those in NR group. Collagen Ⅰ and Laminin in TLD group had a better recovery than those in DGT and NRG group, while the recovery of collagen Ⅳ was the best in DGT group.
CONCLUSION: TLD is superior to DGT on the reversion of pathologically accumulated collagen Ⅰ and Laminin, while DGT is superior to TLD on promoting the metabolism of accumulated collagen Ⅳ.
- Citation: Xu GF, Chu YH, Wang XY, Tian DL, Wang XY, Li PT, Yang JX, Jiang LD. Effect of Tiaogan lipi decoction on alcoholic liver disease in rats. Shijie Huaren Xiaohua Zazhi 2006; 14(24): 2386-2394
- URL: https://www.wjgnet.com/1009-3079/full/v14/i24/2386.htm
- DOI: https://dx.doi.org/10.11569/wcjd.v14.i24.2386
乙醇性肝病机制复杂, 所诱发的肝纤维化轻重不等, 广泛存在于饮酒人群. 一项前瞻性研究发现调肝理脾方能保护肝细胞, 并在一定程度上逆转肝纤维化. 我们将更深入观察其对乙醇性肝病的效果.
SD大鼠,♂, 质量150±5 g, 购自北京维通利华公司; 玉米油购自北京嘉乐福商场; 黄原胶和淀粉购自北京化学试剂公司; 食用乙醇由北京酿酒总公司友好馈赠; 羰基铁和吡唑购自美国Sigma公司; Ⅰ, Ⅳ型胶原和层黏蛋白的多克隆一抗购自美国抗体试剂诊断公司; 二步法试剂盒PV-6001 Kits, ZLI-9030和ZLI9001均购自北京中山公司. 调肝理脾方购自东直门医院中药房(由柴胡、益母草、炙鳖甲、丹参组成), 经过水煎浓缩制成含生药为1220 g/L, 东宝肝泰片是复方药片, 主要成分是S-腺苷蛋氨酸等, 购自东直门医院药房, 由吉林省通化市东宝肝泰片片制药公司生产.
动物分为正常组6只, 模型组12只, 自然恢复组12只, 东宝肝泰片组15只, 调肝理脾方组15只. 通过乙醇混合物灌胃制造模型, 剂量为乙醇每日5 g/kg, 吡唑30 mg/kg, 玉米油3 mL/kg, 羰基铁35 mg/kg, 4 wk后减为15 mg/kg, 少量黄原胶和糊精, 每周灌5 d, 休2 d, 每天1次, 直到第9周结束, 正常饲料, 自由进食、水. 调肝理脾方使用剂量为10 mL/kg, 约相当于体质量为60 kg成年人临床用量的10倍. 东宝肝泰片制成150片/L的混悬液, 使用剂量为10 mL/kg, 剂量约相当于体质量为60 kg成年人临床用量的10倍, 均通过灌胃给予. 治疗从第10周开始, 每日1次, 连续10 d. 灌胃结束后所有动物被处死, 肝脏标本速冻或固定以作为电镜、光镜HE染色、Masson复合染色及分子生物学和生化学检测之用. 每个肝组织切片、脱蜡、Ⅰ, Ⅳ型胶原和层黏蛋白免疫组化染色前采用胰蛋白酶消化处理恢复抗原, 3种细胞外间质分子的电子计算机图像半定量采集和分析在美国3Y公司生产的图像分析系统MIS2000上进行.
统计学处理 所有数据以均数±标准差表示, 统计软件采用SPSS10.0, 单向ANOVA用以决定各组间差异, P<0.05被认为具有显著性差异.
模型动物到第4周出现严重的综合症如精神萎靡、竖毛、消化不良和腹泻、体质量减轻、脱水甚至死亡, 从第5周羰基铁减量后大部分动物得以存活. 自然恢复组动物在造模停止后有所恢复, 精神更活跃, 对周围有兴趣, 似有正常食欲, 体质量快速恢复, 毛发整齐、动作敏捷. 东宝肝泰片组和调肝理脾方组在上述方面反较自然恢复组稍差, 可能与每天灌胃操作的伤害刺激有关.
模型动物肝脏弥漫性脂肪变性, 肝窦狭窄, 肝细胞肿胀或皱缩, 胞质混浊或有空泡, 间质细胞染色质深染、增厚, 核变成卵圆形, 边界清楚. 上述改变在自然恢复组没有大的改善, 而东宝肝泰片组肝窦较宽, 肝细胞轮廓和胞质内容更清晰, 间质细胞核较薄、致密且不规则, 调肝理脾方组肝脏变化与东宝肝泰片组类似, 但整个肝脏组织切片看起来似更加自然, 肝细胞看起来更加丰满而且有活力(图1). HE-Masson复合染色: 除在HE染色看到的以外, 模型动物弥漫性脂肪变性, 肝细胞周围铁丝网格样染色阳性, 中央静脉基底膜增厚, 自然恢复组和东宝肝泰片组与此类似, 但调肝理脾方组似乎较轻(图2).
模型动物肝细胞可见核皱缩, 线粒体肿胀、嵴丢失甚至无嵴, 粗面内质网排列紊乱, 铁颗粒沉积, Mallory小体等. 肝窦内皮细胞轮廓变厚, 细胞器增多, 筛孔减少, 核增厚, 细胞周围有大量胶原原纤维. 星状细胞活化, 外形变成清晰深染的卵圆形, 周围有大量胶原原纤维. 肝窦基底膜清楚形成, 外周有大量胶原原纤维围绕. 在自然恢复组和东宝肝泰片片组肝窦周围胶原原纤维已经减少并接近正常, 但其他改善不大. 调肝理脾方组肝窦基底膜改善, 胶原原纤维也见明显减少, 肝细胞、星状细胞和内皮细胞病理形态似有改善但难以描述(图3).
Ⅰ型: 模型动物肝窦和门管系统基底膜周围可见粗厚深染, 中央静脉基底膜不存在. 自然恢复组和东宝肝泰片组表达较少, 调肝理脾方组表达最接近正常组(图4). Ⅳ型: 模型动物阳性染色较正常动物少, 自然恢复组和东宝肝泰片组有一定恢复, 调肝理脾方组与自然恢复组类似, 东宝肝泰片组最接近正常组(图5). 层黏蛋白: 模型动物显示致密和深染的阳性染色, 主要位于肝窦部位. 自然恢复组几乎无恢复, 东宝肝泰片组有所恢复, 但调肝理脾方组恢复最为显著(图6).各组Ⅰ, Ⅳ型胶原和层黏蛋白免疫组化染色半定量及其比较结果见表1.
乙醇性肝病分乙醇性脂肪肝、乙醇性肝炎、乙醇性肝纤维化和乙醇性肝硬化4种类型, 其共同的损伤机制与脂质过氧化[1]、内毒素[2-5]、乙醛及其所诱发的免疫反应损伤[6-8]、性别状况[9]、铁离子沉积[10-17]以及自由基产生过多[18]、葡萄糖代谢紊乱、DNA损伤等[19]有关. 对乙醇性肝纤维化来说, 一是对其分布情况不清, 二没有特殊针对性治疗. 我们实验探讨的模型[20]完整再现了肝损伤到轻度肝纤维化的病理变化, 其价值在于可能比较符合大量一般饮酒者的肝脏病理变化. 国内外学者曾设计各种方法和药物治疗乙醇性肝病, 经复习文献发现S-腺苷甲硫氨酸、己酮可可碱、metadoxin、多不饱和卵磷脂、细胞色素P4502E1同工酶抑制剂可能较有价值[21], 糖皮质激素和同化激素有副作用, 水飞蓟素对轻型病症的作用正在观察, 对肝硬化无效. Lee et al[22]发现乙醇性肝炎时肝脏蛋氨酸和谷胱甘肽代谢基因表达不正常, 可导致蛋氨酸、S腺苷甲硫氨酸、半胱氨酸和谷胱甘肽代谢异常, 给患者补充这些物质有治疗意义. Rambaldi et al[23-24]报道系统回顾资料未能显示雄性类固醇对乙醇性肝病患者重要的预后和结局有显著性益处. Tome et al[25]报道营养支持、糖皮质激素、抗感染药物、抗氧化剂、抗纤维化药物如秋水仙碱、丙基硫脲嘧啶和抗氧化剂等均未能一致性地证明改善乙醇性肝损害进程. Lieber et al[26-28]总结大量S腺苷甲硫氨酸在狒狒可对抗乙醇肝硬化, 在人类可以降低乙醇性肝硬化患者的死亡率, 并对抗由乙醇、酮体、和脂肪酸诱导细胞色素P4502E1(CYP2E1)所导致的氧化应激反应和乙醇性和非乙醇性脂肪型肝炎. 在啮齿类和非人灵长类乙醇性肝病早期即使饮食合适, 已经有显著的S腺苷甲硫氨酸缺乏, 补充S腺苷甲硫氨酸有助于纠正肝脏缺乏和相关损害, 因此乙醇性肝病早期补充S腺苷甲硫氨酸对肝脏线粒体损伤有益, 这可以在狒狒、其他模型甚至人类实验得到证明. 己酮可可碱是TNF-α的抑制因子, 可降低乙醇性肝炎患者死亡率. 多不饱和磷脂酰胆碱(PPC)是一个从大豆中提取的抗氧化卵磷脂复合物, 其中50%是高级生物可利用的dilinoleoylphosphatidylcholine, 可恢复受损的细胞磷脂膜并恢复其酶活性, 包括磷脂酰乙醇胺转甲基酶. 在狒狒PPC可以激活胶原酶活性并对抗脂质过氧化, 对乙醇性肝炎患者也有益, 对严重饮酒者可以对抗纤维化, 降低合并丙型肝炎患者的ALT. 抗氧化剂水飞蓟素也可以对抗狒狒和部分患者的乙醇性肝硬化, 维生素E也有类似效果, 皮质类固醇和秋水仙碱治疗结果不一, 用长链脂肪酸酯替代中链在实验中和临床上均可以对抗脂肪肝. McClain et al[29]报道外源性S腺苷甲硫氨酸可以减轻肝损害和降低血清TNF-α水平, 且呈现剂量依赖性. Ji et al[19]报道乙醇可以通过半胱氨酸诱发的内质网氧化应激机制导致小鼠肝细胞凋亡和脂肪合成基因表达, 甜菜碱则可以纠正之, 故可以防治乙醇性肝病. Farinati et al[30]报道锌制剂可以防治Wilson病患者血清谷胱甘肽和半胱氨酸的降低以及氧化型谷胱甘肽升高, 抑制脂质过氧化, 提高谷胱甘肽的可利用性, 因而对乙醇性肝病可能有帮助. Bettini et al[31]报道, 熊去氧胆酸450 mg/d治疗6 mo可使乙醇性肝病患者血清酶显著下降, 加上水飞蓟素400 mg/d效果更好. Yan et al[32]报道, fenofibrate可以显著降低乙醇性脂肪肝大鼠肝脏脂肪含量, 同时改善病理, 但对药物诱发者无效. Enomoto et al[33]报道, 镇静安眠药thalidomide可以通过抑制库普弗细胞产生TNF-α而保护肝细胞防止乙醇损伤. Lieber et al[34]报道在狒狒水飞蓟素可以阻碍乙醇诱发的肝纤维化. Lirussi et al[35]报道水飞蓟素b环糊精可以显著改善胰岛素活性并对抗脂质过氧化. Purohit et al[36]报道谷胱甘肽前体s-adenosyl-l-methionine(SAMe)可以修复线粒体谷胱甘肽转运系统, 削弱炎症刺激因子的毒性作用并促进DNA甲基化. Yi et al[37]报道, 环氧合酶参与了乙醇诱发的肝损伤, 其抑制剂celecoxib可以通过降低血栓素B2水平来减轻肝损伤. Rambaldi et al[38]报道, 没有证据表明对乙醇性肝病患者使用丙基硫脲嘧啶有益. Enomoto et al[39]发现过氧化物酶体受体激动剂g拮抗剂pioglitazone可以阻断大鼠肝脏巨噬细胞在饮用乙醇后对增加的LPS的反应, 从而保护肝脏免受损伤. Lambert et al[40]报道, ♂129 SvPCJ小鼠用硫酸锌(锌离子5 mg/kg)预先3次灌胃, 然后口服乙醇1次(6 g/kg), 血清中乙醇浓度上升, ALT上升, 肝脏细胞发生脂肪变性和坏死, ELISA检测发现, TNF-α水平上升, 小肠损害非常显著, 通透性增大, 但在锌制剂治疗后动物肝脏病理变化和TNF-α升高被显著抑制, 小肠通透性显著下降, 提示锌制剂有潜在治疗价值. Aleynik et al[41]报道SD大鼠饲喂乙醇8 wk可以导致S腺苷甲硫氨酸缺乏, 而多不饱和卵磷脂可以纠正之, 恢复谷胱甘肽含量, 从而预防乙醇引起的氧化应激. Lieber et al[42]报道, 412名患者肝脏穿刺结果显示多不饱和磷脂酰胆碱治疗2年不影响乙醇性肝纤维化进程, 但对转氨酶和胆红素恢复有帮助. Oh et al[43]报道, 麦芽提取物有助于减轻慢性乙醇中毒综合征, 帮助恢复, 可以显著提高HDL-C, 对抗服用乙醇后LDL-C、肝脏ALT、三酰甘油和胆固醇升高趋势, 对慢性乙醇性肝病相关病变的预防和恢复有利, 这可能与所含GABA有关. Yang et al[44]报道, 丙酮酸乙酯溶解于含钙离子的林格氏平衡液后使用可以减少肝细胞碎屑样坏死和脂肪变性、降低ALT、脂质过氧化、NF-κB因子活化、TNF-α mRNA表达, 从而减轻急性乙醇中毒小鼠肝脏损害. Senthilkumar et al[45]报道, 氨基己酸可显著抑制脂质过氧化、升高肝脏和脑谷胱甘肽、谷胱甘肽氧化酶、超氧化物歧化酶和过氧化氢酶水平, 血清维生素E和C水平也接近正常, 光镜下肝脏炎症细胞浸润和脂肪变性减轻. McKim et al[46]报道, 可可豆所含的类黄酮可以减轻乙醇所引起的ALT升高、严重的脂肪堆积、轻微感染、肝组织坏死和氧化应急造成的蛋白加合物上升、完全阻断乙醇引起的TNF-α升高. Saygi et al[47]报道, 土木香根水提取物对乙醇性肝、肾和睾丸损伤有轻微治疗效果. Nanji et al[48]报道, 姜黄素能够抑制NF-KappaB依赖基因诱导, 预防实验性乙醇肝病. Yeh et al[49]报道, 当归可抑制慢性摄入乙醇小鼠肝匀浆中丙二醛的含量并保护肝细胞, 可能通过抑制氧自由基产生而诱发的脂质过氧化来实现. Ji et al[50]报道, 中药复方清肝活血汤可以改善厌食、恶心、呕吐和黄疸, 以及降低ALT, AST和甘油三酯, 降低GGT, 改善肝纤维化指标和细胞因子, 减轻肝脏脂质过氧化损害, 明显改善脂肪肝. 该方可以对抗脂质过氧化、稳定细胞膜、调节肝脏脂类代谢, 改善免疫功能, 抗肝纤维化和促进肝脏乙醇代谢.
乙醇性肝病病理机制复杂, 病理变化多样, 因此在治疗上作用于单一环节的药物可能不够理想. 国产复方东宝肝泰片根据现代医学对乙醇性肝病的研究结果设计组成, 含有多种成分, 如S腺苷甲硫氨酸, 长期临床应用证明, 其对乙醇性肝病效果稳定可靠. 我们发现该药新的作用机制, 即他可以促进肝窦毛细血管化的恢复, 特别是对肝窦基底膜Ⅳ型胶原的代谢, 其正向的恢复作用, 且强于调肝理脾方, 但对病理性质的层黏蛋白和Ⅰ型胶原堆积的恢复作用不及调肝理脾方.
中医学"肝"的概念, 复杂深刻而不完全等同于现代医学的肝脏. 如《内经》云: "肝藏血, 体阴而用阳, 喜条达而恶抑郁", 即肝脏可以储藏血液, 按阴阳分类其本质属阴, 但其用则为阳, 而且说明情绪可以影响免疫, 进而影响肝脏病理. 在中医学层面上容易发生的病机有肝气郁结、肝血亏损、肝阳上亢或肝血瘀阻, 可表现为一系列症状和体征, 出现在下列疾病如高血压病、痛经、视物昏花、帕金森病、Wilson病、慢性肝炎、乙醇性肝病、肝纤维化和肝硬化等. 古代先贤说肝病治法最杂, 也印证肝病的机制复杂和难以治疗特点.
很久以前国人祖先就掌握了酿酒技术, 他们把酒作为一种食品饮用, 或作为药品以治疗某些病症, 同时也非常清楚乙醇滥用的弊病. 许多医学文献警告人们滥饮必然伤身. 北京中医药大学东直门医院田德禄教授在总结、提炼文献的基础上, 提出自己的观点, 将乙醇性肝病的中医诊断分为三个阶段: "伤酒"、"酒癖"和"臌胀", 分别对应于急性乙醇中毒和/或乙醇性肝炎、乙醇性肝纤维化和肝硬化. 鉴于乙醇对人体的损伤机制复杂而广泛, 单纯的治疗方法和药物常难以得到理想效果, 田教授从中医理论高度树立"调肝理脾"思想, 重视药物对机体的全面调整, 他认为治疗"酒癖"或者"臌胀"的关键是调节肝的阴阳气血, 进而才能达到保证脾脏运化正常的作用.
调肝理脾方由醋柴胡、益母草、生黄芪等组成, 有疏肝解郁、理脾活血等功效. 柴胡, 为伞形科植物柴胡Bupleurum chinenes的根, 味苦、微辛, 性平, 具有解表退热、疏肝解郁、升举阳气的功效, 主治风热感冒、百日咳、肝郁肋痛、风疹、疮毒节肿等. 柴胡根含挥发油, 柴胡皂苷(saikosaponins, SS) a, c, d, s及多糖, 茎叶含黄酮类, 既往研究发现其具有对抗肝损伤、抗肝纤维化和直接抑制细胞外基质合成等作用. 益母草为唇形科植物益母草Leonurus heterophyllus Sweet的干燥地上部分, 益母草能活血调经、化瘀生新、利尿消肿, 主治月经不调、胎漏难产、行经腹痛及产后瘀阻等, 其主要成分水苏碱和益母草碱, 据认为就是其有效成分. 将益母草用于治疗肝纤维化是田德录教授多年来行之有效的独特宝贵经验, 其理论基础就在于中医认为任、冲、督一源三歧, 肝属冲脉, 任主胞胎, 益母草活血调经功效独特, 几成妇科不可或缺的药物, 与其擅入肝经、擅长调理肝血有密切关系, 田教授创新性地将其用于肝纤维化的治疗, 临床证明功效独特. 黄芪是常用的补益类中药, 可补肝虚, 具有补气升阳、益卫固表等功效. 据报道黄芪含有黄芪总黄酮、总皂甙、黄芪多糖等有效成分, 可以对抗脂质过氧化、保护肝细胞、抑制肝星状细胞增殖、抗肝纤维化和肝硬化等, 调肝理脾方早期的前瞻性研究提示该方有保护肝细胞和抗脂质过氧化作用, 可能对肝纤维化有逆转作用. 我们研究发现该方可以促进肝窦基底膜病理性Ⅰ型胶原和层黏蛋白分解, 也能促进Ⅳ型胶原含量恢复正常, 且表明复方条件下各个药物间可能存在协同作用, 其具体特点尚待后续报道.
总之, 对乙醇性肝病来说, 治疗方面单一药物往往不如合理的复方照顾周全, 但中医学的立法处方需要多年经验积累和深厚理论造诣和指导. 调肝理脾方有自己的特点, 价格低廉, 对肝窦部位Ⅳ型胶原、层黏蛋白和Ⅰ型胶原代谢有一定正向影响, 临床辩证合适, 可以考虑酌情使用, 以便进一步观察疗效, 并加以改进使之更好地为患者服务.
乙醇性肝病最重要的病理形态学变化是由轻到重的纤维化, 而一般 饮酒者发生大面 积肝细胞坏死的可能性和几率并不高, 这种纤维化发生是围绕肝窦, 肝窦毛细血管化和窦周纤维化是乙醇性肝病基础性改变, 其成分如何改变, 受何种因素影响就成为重要的问题.
虽然机制研究更加复杂深入, 但形态改变的基础仍然是围绕基质金属蛋白酶及其抑制物系统来开展, 而形态改变是真正影响患者预后的决定因素. 对临床来说如何确定可靠的药物、明确药物作用机制最有价值.
目前国内外相关报道很多. 西医多使用单方或化合物观察, 效果、机理均比较确实可 靠. 中医偏重于复方, 不论从中医理论探索、病因病机分析、理法方药的组成思路还是实际临床效果方面来看, 都需要更多更踏实的工作.
其实中医临床效果好的在动物不一定效果好, 反之亦然. 调肝理脾方优势在于价格便宜、效果较全面, 对证的话可以进一步使用、观察.
调肝理脾: 含义比较复杂, 中医认为"肝藏血, 体阴而用阳, 主疏泄, 开窍于目, 其华在爪, ......为罴极之本"等, 是对活体功能的观察总结, 理论层面肝血肝气皆"可调". 肝脾的关系是"见肝之病, 知肝传脾, 必先实脾", 肝病肯定影响脾胃, 通过调理肝血肝气来调理脾胃, 而不采取直接"健脾、醒脾、益气"等方法, 是理论创新, 体现在中药选用、份量斟酌和君臣佐使的安排上;
肝窦毛细血管化: 肝血窦转变为连续毛细血管, 发生于各种肝损伤过程中, 时间上比较早, 比较持续存在, 影响肝细胞功能最重要、最原始、最基础的形态学改变, 肝硬化病人临床好转的基础可能与此逆转有关, 该过程牵涉到的最关键的三种纤维成分是: Ⅰ型胶原、层黏蛋白和Ⅳ型胶原.
电编:李琪 编辑:潘伯荣
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