Reye综合征病理学研究——光镜电镜观察

作者回顾性研究了我室50年收集的410病病理学上诊断为小儿肝脂肪变性病例，其中37例根据美国控制中心的诊断标准诊断为Reye综合征（RS）.对RS作了组织学和超微结构的病理学研究，显示主要病理变化为：弥漫性微泡性肝脂肪变性（泡沫状肝细胞）和肝细胞线粒体损伤。讨论了RS的病理诊断及鉴别诊断，线粒体损伤在发病中的作用和病毒感染、水肠酸制剂的应用与发病关系。     

丹参对急性酒精性肝损伤肝组织保护作用的研究

目的观察丹参对酒精所致大鼠急性肝损伤肝组织的保护作用。方法大鼠分为正常组(以正常饮食、饮水喂养)、模型组(连续6天高浓度白酒灌胃)、丹参低、中、高剂量组(白酒灌胃造模后,给予丹参腹腔注射)。9天后处死大鼠,观察大鼠肝脏的组织病理学改变及肝细胞的超微病理学改变。结果模型组大鼠的肝组织呈现明显的水样变性和脂肪变性,并可见少量片状肝细胞坏死。而丹参组肝细胞未见坏死改变,水样变性和脂肪变性程度也较轻,以高剂量丹参组最为显著。结论丹参对急性酒精性肝损伤肝组织有一定的保护作用。     

丙戊酸钠对大鼠肝细胞毒性作用的形态学观察

目的:为丙戊酸钠(VPA)肝毒性是否与剂量与合并用药有关提供形态学依据。方法:利用肝细胞原代培养技术,分别在光镜及电镜下观察不同浓度VPA及VPA与苯巴比妥钠(PB)或卡马西平(CBZ)合用对肝细胞一般形态及超微结构的影响。结果:光镜下观察细胞形态、核膜、核仁,细胞的折光性,各用药组与对照组相比均无明显改变。电镜对超微结构的观察:对照组肝细胞的细胞核完整,胞浆内线粒体丰富,呈椭圆形,可见内质网。与对照组相比,当VPA浓度为50mg/L时,可见肝细胞部分线粒体略肿胀,呈球形,嵴减少;当VPA浓度为100mg/L时,可见肝细胞线粒体肿胀略为明显,嵴减少,部分肝细胞内有少量脂滴;当VPA浓度为200mg/L时,可见肝细胞部分线粒体呈空泡状,肝细胞内脂滴增多。单独应用VPA组与合并用药组相比,合并用药组可见到内质网扩张较为明显,线粒体损伤程度和脂肪变性程度与单独应用VPA组没有明显加重。结论:VPA损害线粒体结构,并可以引起细胞脂肪变性,且存在剂量依赖关系。在治疗范围内,VPA与PB或CBZ合用没有加重肝细胞的损伤。     

肝舒乐片对非酒精性脂肪肝大鼠肝细胞线粒体能量代谢的影响

目的研究肝舒乐片对非酒精性脂肪肝(NAFL)大鼠肝细胞线粒体能量代谢的影响。方法用高脂饲料诱发大鼠NAFL模型,同时给予肝舒乐片干预,光镜下观察大鼠肝组织病理形态和琥珀酸脱氢酶(SDHase)的表达,电镜下观察肝细胞超微结构并行立体计量学分析,检测肝组织甘油三酯(TG)、总胆固醇(TC)、游离脂肪酸(FFA)含量,并与对照组比较。结果肝舒乐组的肝组织脂肪变性与肝细胞超微结构明显改善,免疫组化表明其显著促进脂肪肝肝细胞SDHase的表达,同时肝组织TG、TC、FFA含量降低,与模型组相比差异均有统计学意义(P0.05)。结论肝舒乐片能有效防治NAFL,其机理可能与增强肝细胞线粒体能量代谢有关。     

肝活检与B超诊断脂肪肝的对比研究

目的 评估肝活检与B超在脂肪肝诊断中的意义.方法 对比分析62例B超检查未诊断为脂肪肝但经肝穿刺活组织检查诊断为肝细胞脂肪变性患者的结果, 并结合肝功能、血脂、血糖、体重指数进行分析.结果62例B超检查未诊断脂肪肝的患者, 经肝穿刺活组织检查, 提示肝细胞脂肪变性5%33%.其中B超检查提示肝实质回声未见异常23例, 肝实质回声稍增粗欠均18例, 肝实质回声稍细密增强17例, 肝脏弥漫性损伤4例, 分别占37.01%、29.03%、27.42%、6.45%;病理提示5%≤肝脂肪变性≤19%有45例, B超检查提示肝实质回声未见异常18例, 肝实质回声稍增粗欠均8例, 肝实质回声稍细密增强17例, 肝脏弥漫性损伤2例, B超改变以肝实质回声未见异常和肝实质回声稍细密增强为主;病理提示20%≤肝脂肪变性≤33%有17例, B超检查提示肝实质回声未见异常6例, 肝实质回声稍增粗欠均5例, 肝实质回声稍细密增强5例, 肝脏弥漫性损伤1例, B超改变主要表现为肝实质回声未见异常、肝实质回声稍细密增强和肝实质回声稍增粗欠均.分析患者的肝功能、体重指数、血脂和血糖对B超改变的影响, 通过无序多分类Logistic回归分析发现谷氨酰转移酶、碱性磷酸酶、体重指数、甘油三酯和低密度脂蛋白胆固醇的值越大, 越容易导致肝脏弥漫性损伤;脂肪变性程度越大越容易导致肝脏弥漫性损伤.结论 对脂肪肝的诊断, 当肝细胞脂肪变性低于1/3时, B超检查不能表现出脂肪肝的特征性改变, 应密切观察B超或行肝穿刺组织学检查以明确脂肪肝诊断.     

L-肉碱对幼鼠丙戊酸肝毒性的保护作用及其机理探讨

目的:研究L-肉碱对丙戊酸(VPA)肝毒性的保护作用及相关机制.方法:采用VPA及苯巴比妥钠(PB)灌胃制作幼鼠VPA肝损伤的动物模型,同时以L-肉碱作为干预措施,观察其对实验动物肝脏,尤其肝线粒体功能的保护作用.化学比色法测定血氨、L-肉碱、肝脏凝血因子合成功能、线粒体呼吸酶系等;高效液相色谱、流式细胞仪分别检测VPA与PB血药浓度及肝线粒体跨膜电位(MMP);采用Oil-Red-O染色观察肝细胞脂肪变性.结果:(1)VPA/VPA PB组肝线粒体呼吸链关键酶琥珀酸脱氢酶(SDH)及细胞色素氧化酶(CCO)活性与对照组均存在非常显著性差异(P＜0.01),而补充L-肉碱对SDH和CCO活性均有明显保护作用;(2)VPA PB组MMP下降21.47％,与对照组差异显著(P＜0.05).L-肉碱能有效维护MMP正常;(3)在VPA PB组,凝血因子PT、TT、APTF、Fbg,以及血氨和L-肉碱含量均有显著改变.补充L-肉碱改善肝脏凝血因子合成、使血氨正常;(4)Oil-Red-O染色显示,VP/VPA PB组均出现门管区为主的肝细胞脂肪变性,脂肪细胞数分别高出对照组9.2倍和15.7倍,差异非常显著(P＜0.01).L-肉碱干预后脂肪变性肝细胞数均有非常显著减少(P＜0.01),表明L-肉碱能有效的阻止肝细胞脂肪变性.结论:L-肉碱对VPA肝损伤有较好防治作用,这一作用主要是通过阻止肝脂肪沉积和保护线粒体功能而实现.另外,当VPA与肝酶诱导剂联合运用时,虽然VPA血药浓度值可能不高,但由于肝酶诱导剂使具有非常强肝毒性的VPA中间代谢产物明显增加,所以仍应密切监测其肝毒副作用.     

水飞蓟宾治疗慢性乙型肝炎合并脂肪肝疗效观察

<正>慢性乙型肝炎是由乙型肝炎病毒感染引起的,乙型肝炎病毒的复制使肝细胞持续慢性损伤,致细胞外基质可逆性沉积,导致肝纤维化,甚至演变为肝硬化[1]。脂肪肝的发病机制是胰岛素抵抗等初次打击导致肝细胞脂肪变性,氧应激、脂质过氧化损伤等二次打击诱发肝细胞坏死和炎症浸润,进而激活肝星状细胞诱发肝纤维化,最终可导致肝硬化和肝细胞癌,还能促进心脑血管事件的发生。因此,治疗慢性乙型肝炎合     

抑制枯否细胞可以减轻鼠肝在冷保存中的脂质过氧化损伤

目的:研究抑制枯否细胞对冷保存的鼠肝枯否细胞和肝细胞线粒体的影响。方法:实验组连续2 d静注氯化钆,7 mg/kg,对照组静注等量生理盐水。3 d后手术取肝,保存时间分别为1,2,3和4 h。观察各组枯否细胞和肝细胞线粒体的形态变化,测定肝组织和肝细胞线粒体脂质过氧化物(LPO)的含量。结果:对照组枯否细胞表现为细胞膜突起增多,细胞内颗粒物质增多等。肝细胞线粒体普遍肿胀,内膜嵴断裂,空泡形成以及破坏等。实验组肝组织和肝细胞线粒体脂质过氧化程度在冷保存1 h和2 h显著低于对照组(P<0.05)。结论:抑制枯否细胞对鼠肝的冷保存损伤有一定的保护作用。     

《非酒精性脂肪肝诊断标准(草案)》应用的体会(附30例病理分析)

《非酒精性脂肪肝诊断标准 (草案 )》〔1〕已在临床实施 ,我们根据此标准对肝穿刺活检确诊的 30例脂肪肝进行病理学回顾性分析。1　材料与方法1999年 1月～ 2 0 0 2年 6月 ,我院病理科确诊的脂肪肝 30例 ,作ＨＥ切片。参照《非酒精性脂肪肝诊断标准(草案 )》进行分类、分级与分期。2　结果本组单纯性脂肪肝 15例 (其中轻度 8例、中度 5例、重度 2例 ) ,肝细胞脂肪变 2例 ,脂肪性肝炎伴肝纤维化13例 (其中轻度 9例、中度 4例 )。2 .1　单纯性脂肪肝　肝细胞脂肪变性主要分布在肝小叶 2～ 3区 ,脂肪空泡大多为大泡性、部分呈小泡性或混合性改…     

酒精是意大利北部丙型肝炎患者发生肝细胞脂肪变性和肝纤维化的重要协同因素

慢性丙型肝炎(CH C)患者发生肝细胞脂肪变性可能是病毒和宿主因素共同作用的结果。本研究旨在阐明:①脂肪变性与宿主或病毒因素的关系;②CH C患者肝细胞脂肪变性与肝纤维化的相关性。测定了连续349例患者的肝脂肪变性程度。通过肝脏活检对患者进行了病毒学检查和实验室分析,并且记录了患者饮酒量的情况。Logistic回归分析显示脂肪变性分别与下列因素独立相关:基因型3a型(OR3.5),取活检时的酒精摄入量(OR2.6),年龄>35岁(OR2.7)。在多变量分析中,发现肝纤维化与酗酒史(OR3.7)、年龄>44岁(OR2.2)相关。总体而言,肝脂肪变性分级和肝纤维…     

Psychiatry.

Reye's syndrome (encephalopathy and fatty liver) is generally considered a disease of children. Four patients, aged 16, 18, 19, and 23 years, with Reye's syndrome were initially seen by internists. A viral prodrome followed by vomiting and encephalopathy without focal neurological signs or jaundice clinically suggested Reye's syndrome. Normal findings of CSF examination (except for increased opening pressure), abnormal findings of liver function tests, and increased blood ammonia further supported the diagnosis. None was hypoglycemic. Reye's syndrome was related to influenza B virus in three patients and to Varicella in another. Three patients survived. Reye's syndrome may be seen intially by general practitioners, emergency room physicians, internists, or psychiatrists. The importance of considering this syndrome in the differential diagnosis of unexplained encephalopathy in adults is stressed.     

Defects of metabolism of fatty acids in the sudden infant death syndrome

Two hundred consecutive cases of the sudden infant death syndrome were reviewed for the presence of fat in the liver; 14 showed diffuse panlobular microvesicular fatty change indistinguishable from that found in Reye's syndrome. Samples of frozen liver were available in five of the 14 cases; histochemical analysis showed well preserved cytochrome oxidase and succinate dehydrogenase activity in all five, uncharacteristic of Reye's syndrome. Fatty acyl-coenzyme A dehydrogenase activity in the liver was assayed biochemically in two of the same five cases with severe hepatic fatty infiltration; both showed a defect in medium chain acyl-coenzyme A dehydrogenase activity using the substrate octanoyl-coenzyme A. Both cases also showed cerebral oedema in association with fatty infiltration of renal tubules, myocardium, and skeletal muscle, characteristic of Reye's syndrome. It is concluded that diffuse panlobular microvesicular fatty change of the liver in victims of the sudden infant death syndrome, although essentially non-specific, indicates that the state of mitochondrial enzymes should be investigated.     

Public Health Service study of Reye's syndrome and medications. Report of the main study

Between January 1985 and May 1986, following completion of a pilot study, a main study concerning the possible association between Reye's syndrome and salicylates was conducted. Twenty-seven patients with stage II or deeper Reye's syndrome whose diagnoses were confirmed by an expert panel and who had appropriate antecedent illnesses (chickenpox, respiratory illness, or gastrointestinal illness) prior to the onset of Reye's syndrome were compared with 140 controls matched for age, race (black or not black), and type and timing of onset of antecedent illness. Controls were selected from the same hospital, emergency room, or school as case-patients or were identified by random-digit telephone dialing. As in the pilot study, a strong statistical association with ingestion of salicylates during the antecedent illness and prior to the onset of Reye's syndrome was observed (odds ratio, 40; lower 95% confidence limit, 5.8). Analysis of the independent risk of aspirin and nonaspirin salicylates revealed a significant association with aspirin (odds ratio, 26; lower 95% confidence limit, 6.4); the independent risk of nonaspirin salicylates could not be assessed because only two cases were not exposed to aspirin. Assessment of epidemiologic issues of concern, including case-control differences in the severity of the antecedent illness, did not explain the high odds ratios that were observed. The high percentage of patients with Reye's syndrome exposed to salicylates (greater than or equal to 90%) in this and prior studies suggests that, though the reported incidence of Reye's syndrome has declined in recent years, concomitant with a decline in salicylate use among children, a majority of Reye's syndrome cases may be attributable to salicylate use.     

Reye's syndrome: assessment of intracranial monitoring

Direct measurements of arterial blood pressure and intracranial pressure were recorded in 39 patients aged 3.6 months to 5 years 11 months with Reye's syndrome judged to be stage 2 or beyond. Of 33 patients who survived, 27 made a full recovery and six were severely handicapped. Measurement of cerebral perfusion pressure, which is greatly reduced in the more severe forms of Reye's syndrome, was a better guide to prognosis and management than intracranial pressure alone. The findings emphasise that maintenance of cerebral perfusion pressure is essential if mortality and morbidity are to be reduced. Intracranial monitoring is mandatory in all but the mildest cases of Reye's syndrome.     

脑损伤和急性肝炎病人血清过氧化脂质的研究—血清过氧化脂质与Reye综合征(英文)

Reye综合征是由Douglas,Reye等人在1963年描述的。然而,Reye综合征的原因现在还不清楚。吉田(1989)提出损伤性介质链(辛酸)和高血清过氧化脂质水平,可能与Reye综合征细胞毒性作用的发病机制有关。我们分别对30例脑损伤和急性肝炎病人血清过氧化脂质进行了研究,得到如下结论:①仅有单纯的血清过氧化脂质水平增高,不会发生脑功能紊乱。30例急性肝炎病人的血清过氧化脂质水平很高(P<0.01),但是,他们的脑电图与对照组无明显差异(P>0.05);②脑损伤发生的同时,血清过氧化脂质水平的增高和肝功能紊乱程度一致,30例脑损伤病人的血清过氧化脂质和GOT、GPT水平均高于对照组(P<0.01)。在Reye综合征发病机制中,血清过氧化脂质的作用应当进一步研究。     

大鼠肝细胞线粒体周围内质网的三维重建

目的：研究肝细胞线粒体与内质网的空间结构关系。 方法：通过连续超薄切片重建线粒体与其周围内质网的三维模型,结果：连续超薄切片和三维模型显示：除极少量的线粒体与脂滴直接接触外,几乎每个线粒体都被内质网所包裹,大多数线粒体周围既有RER又有小囊泡状SER,少数线粒体则仅有小的SER。这些内质网与线粒体紧贴如同线粒体外壳,二者的间隙小于30nm,其间无任何其它细胞器。结论：肝细胞线粒体通常在内质网包绕下执行生理功能,二者形成的结构和功能紧系的整体。     

Inborn errors of metabolism in children referred with Reye's syndrome. A changing pattern

Genetic disorders were identified infrequently among children presenting with Reye's syndrome in the past. During a two-year period, we evaluated four consecutive patients referred for intensive care of Reye's syndrome. A standard investigation for inborn errors of metabolism revealed that two patients had enzymatic defects of fatty acid oxidation, and the other two had partial deficiencies of ornithine transcarbamoylase. None had experienced a previous episode of Reye's syndrome, and three of the four had been entirely healthy in the past. Our experience suggests that as the incidence of Reye's syndrome has decreased, patients with its clinical features are now more likely to have manageable inborn errors of metabolism (eg, disorders of ureagenesis, ketogenesis, and branched-chain amino acids).     

大鼠肝细胞线粒体周围内质网的体视觉分析

目的：D直细胞与其周围内质网的结构关系,方法：使用钻占石刀对肝组织进行连续切片,电镜下观察线粒体及其周围内质网的三维结构。对肝细胞细胞器,特别是线粒体及其周围内质网进行体视学分析。结果：几乎所有的线粒体都在内质网的包绕下工作,在整个肝细胞内有26％的RER的32％的SER贴附近线粒体的周围。结论：肝细胞线粒体通常在内质网在包绕下执行生理功能,二者是结构和功能紧密联系的整体。     

复方柴胡汤加减对大鼠酒精性肝损伤形态学和线粒体的定量研究

目的：探讨中药复方对酒精性肝损伤的防护作用。方法：形态学观察（光镜,电镜）应用MPIAS－500病理图文分析系统做线粒体定量分析（面积,周长,等效直径,平均光密度）,结果：光镜损伤组肝细胞破坏明显,呈气球样变,有酒精小体,汇管区有炎细胞浸润,而防治组与正常组相似,肝小叶排列规则,细胞体积大,分界清晰,电镜损伤组细胞不规则,胞质疏松,含大量脂滴,而防治组与正常组相似,核大而规则,含丰富的细胞器,无或少量脂滴,线粒体各指标损伤组与防治组差异显著（P＜0．01）。结论：本中药复方对酒精性肝损伤具有一定的防护作用。     

水下冲击波致犬肺损伤的病理学观察

目的探讨水下冲击伤后犬肺的病理学改变.方法成年杂种犬37只,布放于离爆心3.5～17.5 m处,分别用200、500 g和1 000 g TNT水下3 m爆炸,水中压力传感器测定冲击波物理参数,观察伤后肺的大体形态学改变以及光镜和电镜下组织结构的变化.结果肺损伤的发生率达83.7%,大体形态学改变主要为肺出血、肺水肿及少数肺撕裂;光镜下可见肺泡腔内有大量的红细胞及纤维蛋白渗出;电镜下可见肺泡壁毛细血管内皮细胞破坏严重,部分线粒体出现空泡变与髓鞘样结构,核膜不完整等特点.结论严重的肺出血和肺水肿可能为动物水下冲击伤早期死亡的主要原因.