线粒体肌病的病理分析

目的:探讨线粒体肌病患者的临床特点及其组织化学病理、电镜超微结构病理特征,提高对本病的确诊率。方法:对4例患者肌活检组织进行光镜和电镜超微病理观察。结果:3例患者肌活检组织MGT染色光镜检查发现破碎红纤维,4例患者肌活检组织电镜下发现线粒体堆积于肌原纤维间及肌膜下,形态变异,均可见晶状包涵体。结论:MGT染色发现破碎红纤维,电镜下线粒体堆积、形态异常,特别是线粒体内晶状包涵体,对本病的诊断有重要价值。     

糖原累积在线粒体肌病中的意义

目的 结合线粒体肌病超微结构变化的特征，探讨该病的病因和可能的发病机制。方法 对2例线粒体肌病患者腓肠肌活检组织进行光镜和电镜超微病理观察。结果 患者病变肌纤维内，线粒体存在形态独特的类品格包涵体，符合诊断特征；另外，肌纤维间还存在大量糖原颗粒聚集。结论 线粒体内不同形态的类品格包涵体可能代表了不同种蛋白质的堆积，或是同一种蛋白质异常合成的不同时期的表现；糖原颗粒的异常增多，是继发于线粒体功能障碍所致。     

三例成年起病的线粒体肌病临床与病理研究

目的报道3例曾被误诊为多发性肌炎而后被确诊为成年起病的线粒体肌病的临床、MRI及病理学表现. 方法对3例病人进行临床、电生理、MRI和肌肉活检特殊染色、组织酶学等病理检查. 结果3例患者均表现为四肢近端肌无力与肌萎缩,肌酶升高,EMG示肌源性损害,MRI示近端肌肉萎缩较明显.肌肉病理学检查,MGT特染及NADH-TR和SDH组织酶学染色中发现典型的"玻碎红纤维",电镜证实肌纤维胞浆内线粒体增多.结论对临床成年起病的进行性对称性四肢近端肌无力与萎缩的患者应考虑线粒体肌病的可能;特殊染色及组织酶学在诊断线粒体肌病中起重要作用,激素治疗可能有效.     

晚发型酸性麦芽糖酶缺陷病的肌肉酶组织化学和超微结构

目的 :探讨酸性麦芽糖酶缺陷病的肌肉酶组织化学和超微结构特点。方法 :用酶组织化学方法观察快速冷冻后的肌肉组织切片 ,用透射电镜观察其超微结构。结果 :①光镜下见大量空泡肌纤维 ,空泡内可见嗜碱性絮状或粗颗粒状物质 ,形成镶边空泡 ;②ATP酶染色示空泡主要累及Ⅱ型肌纤维。空泡化肌纤维的酸性磷酸酶活性明显增强 ,PAS阳性物质轻度增多 ;③电镜观察发现肌原纤维间大量糖原及髓样结构 ,外包单位膜。含变性线粒体及糖原颗粒的自噬空泡多见。在肌间毛细血管的周细胞和间质成纤维细胞内发现多个糖原积聚区。结论 :肌活检超微病理观察和酶组织化学检测对酸性麦芽糖酶缺陷病有明显的特异性 ,对本病的诊断有重要价值。     

Joseph病黄氏家系患者骨骼肌中线粒体超微结构的电镜观察

对Joseph病黄氏家系不同型的3例患者的肌肉活检样品作了电镜观察,发现3例病肌均有不同程度的萎缩、变性、坏死等超微结构改变。线粒体主要表现为在肌膜下和肌纤维溶解坏死灶内聚集、增生,有的线粒体肿胀、空泡化;有的皱缩、坏死。在萎缩变性的肌纤维中可见剖巨大线粒体和畸形线粒体,有的线粒体内有包涵体形成。对这些病变结合临床进行了分析和讨论。     

三例成年起病的线粒体肌病临床与病理研究

目的：报道3例曾被误诊为多发性肌炎而后被确诊为成年起病的线粒体肌病的临床、MRI及病理学表现。方法：对3例病人进行临床、电生理、MRI和肌肉活检特殊染色、组织酶学等病理检查。结果：3例患者均表现为四肢近端肌无力与肌萎缩，肌酶升高，EMC示肌源性损害，MRI示近端肌肉萎缩较明显。肌肉病理学检查，MGT特染及NADH-TR和SDH组织酶学染色中发现典型的“玻碎红纤维”，电镜证实肌纤维胞浆内线粒体增多。结论：对临床成年起病的进行性对称性四肢近端肌无力与萎缩的患者应考虑线粒体肌病的可能；特殊染色及组织酶学在诊断线粒体肌症中起重要作用，激素治疗可能有效。     

常染色体隐性遗传杆状体肌病一个家系的临床与病理分析

目的 探讨杆状体肌病(NM)的临床和病理特点.方法 对1个常染色体隐性遗传NM家系临床资料进行回顾性分析,并观察肌组织病理和超微结构.结果 4例患者均为出生时或胎儿期起病,其中2例表现为运动发育迟滞,全身肌肉容积下降,其头面部特征包括长脸、帐蓬形嘴、高腭弓;2例累及呼吸,于新生儿期死亡.光镜显示肌纤维萎缩,Ⅰ型纤维优势化,改良Gomori三色(MGT)和HE染色可见肌纤维胞质中红染物质;电镜显示肌丝排列紊乱,肌膜下及核周杆状结构.结论 NM是一类具有明显临床和病理异质性的先天性肌病,其诊断依靠典型的临床和病理特点.     

先天性肌营养不良症患儿肌肉组织超微结构观察

目的研究先天性肌营养不良症（congenital muscular dystrophy,CMD）患儿肌肉的超微结构。方法取1例CMD患儿腓肠肌组织,经常规电镜样品制备后进行观察。结果CMD肌纤维出现下列超微结构改变：①肌纤维萎缩;②肌纤维Z线断裂,肌丝排列紊乱,肌膜下出现肌质块;③有些肌纤维坏死;④线粒体基质有晶格状包涵物。结论本病例出现的各种形态学改变,提示CMD的病情发展是一种渐进的过程。同时,它也可影响线粒体合成ATP功能。     

线粒体肌病的超微结构观察

线粒体肌病是指由于线粒体结构异常或功能缺陷而引起的肌肉能量代谢障碍的一组肌病。过去认为本组疾病罕见，随着肌活检，组织化学染色、超微结构观察及生化检测的进展，对本组疾病的诊断和认识水平有了提高，发现本病决非少见病，但很容易误诊其它疾病，如重症肌无力、多发性肌炎、进行性肌营养不良等Ⅲ。我们利用电镜对4例线粒肌病，1例线粒体脑肌病活检组织进行超微结构观察分析。并对该病的临床表现、超微结构改变及病因进行初步探讨。     

线粒体脑肌病合并脂质沉积性肌病1例报告并文献复习

目的 探讨线粒体脑肌病和肉毒碱缺乏的关系.方法 报道1例合并脂质沉积性肌病的线粒体脑肌病患者的临床和病理特点,并复习相关文献.结果 患者主要表现为癫痫大发作和四肢无力,激素治疗效果好.肌肉病理改变特点是许多肌纤维内可见细小空泡,被脂滴填充和较多不典型破碎红纤维(RRF).电镜下见大量脂肪滴,呈串珠样和片状分布;并出现线粒体增多和结构异常,可见嗜锇小体的形成.结论 此患者可以诊断为线粒体脑肌病合并脂质沉积性肌病,其发病机制可能是线粒体呼吸链的氧化缺陷使脂酰辅酶A过度聚集,导致继发性肉毒碱的缺陷.     

MITOCHONDRIAL MYOPATHY AND MITOCHONDRIAL ENCEPHALOMYOPATHY

This paper is the first report of mitochondrial encephalomyopathy and mitochondrial myopathy diagnosed in China. It includes l case of mitochondrial encephalomyopathy with lactic acidemia and stroke-Iike episodes (MELAS), 5 cases of mitochondrial myopathy with skeletal muscles predominantly involved, and 2 cases of mitochondrial myopathy with external ocular muscles predominantly involved. The diagnosis was confirmed by muscle biopsies which revealed the "ragged-red-fiber" CRRF) in modified Gomori trichrome CMGT) stain, accumulation of lipie droplets in oil-red-O stain in frozen sections, and aggregates of abnormal mitochondria with complex paracrystalline inclusions and distorted cristae and osmiophilic dense bodies in their matrix in electron microscopy.     

不同年龄人群肌肉组织中7种线粒体酶的表达差异

目的：探讨年轻人与中老年人肌肉中线粒体电子传递链和胞质中一些关键酶的表达差异。方法：收集7例年轻人及33例中老年人颈部肌肉标本,透射电镜观察两组肌肉中线粒体形态学变化,免疫组织化学染色和蛋白质印迹检测NADH氧化还原酶辅酶1[NADH dehydrogenase（ubiquinone）1 alpha subcomplex 1,NDUFA 1],琥珀酸脱氧酶复合体铁硫亚基（succinate dehydrogenase complex,subunit B,SDHB）,细胞色素b（cytochrome b,Cytb）,细胞色素C氧化酶（cytochrome C oxidase,COX）,V型H^＋ATP酶（vacuolar—type H^＋-ATPase,V—ATPase H）,苹果酸脱氢酶（cytosolic malate dehydrogenase,MDH）、短链羟烷基-辅酶A脱氢酶（hydroxyacyl—coenzyme A dehydrogenase,HADHSC）的表达情况。结果：与年轻人相比,中老年人肌肉中线粒体体积增大,空泡增多,嵴排列紊乱,出现类结晶状包涵体;NDUFA1、SDHB、Cytb、COX、V—ATPaseH表达量明显降低（P均〈0．05）,但MDH及HADHSC的表达差异无统计学意义;蛋白质印迹结果与免疫组织化学结果相一致。结论：肌肉组织中线粒体的形态和关键酶的表达随年龄的增加出现明显改变,可能在衰老过程中起到重要作用。     

充血性心肌病的心肌组织学及超微结构观察——附四例尸检心脏报告

应用光镜、电镜观察四例临床已确诊的黑人充血性心肌病尸检心脏改变,特征是心脏显著扩大,心壁稍增厚但松软,肌纤维肥大,间质纤维组织增生,肌原纤维排列紊乱或溶解,Z 带异常,线粒体数量增多,大小不一,线粒体内可见平行致密带状物及基质内致密的包涵物以及其他退行性变,这些病变虽然不是充血性心肌病特有的变化,但与其他一些心脏疾病包括肥厚性心肌病所见病变有所不同,如能结合临床所见,可作出肯定的诊断。在线粒体内见到包涵物及平行致密带状物,作者认为可能是饮酒引起的充血性心肌病的一种较有特征性的形态学改变。     

清开灵对大鼠脑细胞凋亡的保护作用

目的探讨清开灵注射液对大鼠局灶性脑缺血再灌注损伤细胞凋亡的保护作用。方法48只SD大鼠随机分为4组:假手术组、模型组、清开灵注射液A组(12.8mg/kg)、清开灵注射液B组(4.3mg/kg)。线拴法制作大鼠脑缺血再灌注模型,再灌注22h进行神经功能评分,再灌注24h后,应用化学比色技术检测线粒体琥珀酸脱氢酶(SDH)活性的变化,应用Hoechst33258荧光染色检测脑细胞凋亡。结果模型组大鼠脑缺血再灌注后神经功能障碍症状加重,脑组织线粒体SDH活性明显降低(P<0.05),皮质脑细胞凋亡增多。清开灵注射液干预后,神经功能障碍症状明显改善,可以促进线粒体SDH活性的恢复(P<0.05),细胞凋亡减少。结论清开灵注射液保护脑细胞凋亡,部分是通过促进线粒体SDH活性恢复、保护线粒体整体功能起作用的。     

锰对大鼠肝脏线粒体氧化损伤的作用机制

目的:观察不同剂量的锰对大鼠肝脏线粒体的氧化损伤作用,探讨其相关机制。方法:将24只雄性SD大鼠随机均分为对照组和MnCl₂低、中、高剂量组,分别腹腔注射生理盐水和2、8、32 g/kg MnCl₂溶液,每天1次,连续30 d后取大鼠肝组织测定线粒体PT孔、线粒体膜肿胀度、线粒体膜电位、琥珀酸脱氢酶(SDH)、细胞色素C、羟自由基(OH·)和谷胱甘肽过氧化物酶(GSH-PX)。结果:各组间肝线粒体PT孔差异均有统计学意义(P<0.01);MnCl₂高剂量组线粒体膜肿胀度小于对照组和MnCl₂低剂量组(P<0.05);MnCl₂高剂量组线粒体膜电位光密度均低于其他3组(P<0.05~P<0.01)。与对照组和MnCl₂低剂量组相比,MnCl₂中、高剂量组肝线粒体SDH均下降(P<0.01),且MnCl₂中、高剂量组间差异亦有统计学意义(P<;与对照组和MnCl₂低剂量组相比,MnCl₂高剂量组肝线粒体细胞色素C上升(P<0.05)。MnCl₂高剂量组肝线粒体OH·显著高于其他3组(P<0.01);与对照组比较,MnCl₂低、中、高剂量组大鼠肝线粒体GSH-PX显著降低(P<0.05)。结论:锰可导致线粒体氧化损伤,引起大鼠肝线粒体PT孔开放、膜电位下降,SDH、GSH-PX降低,细胞色素C、OH·显著升高,对机体产生毒性作用。     

硒多糖、亚硒酸钠对大鼠肝线粒体酶的影响及其拮抗亚砷酸钠毒性作用的机理

采用体内、体外实验方法研究了硒化合物（硒多糖、亚硒酸钠）和亚砷酸钠对大鼠肝线粒体丙酮酸脱氢酶、琥珀酸脱氢酶、谷胱甘肽过氧化物酶的活性以及对肝线粒体膜脂质过氧化、还原型谷胱甘肽含量的影响，探讨了其作用机理。结果表明：硒化合物可明显拮抗亚砷酸钠对线粒体丙酮酸脱氢酶、琥珀酸脱氢酶活性的抑制作用，且硒多糖的抑制作用较亚硒酸钠强。这种拮抗作用在防治砷中毒方面具有重要意义。     

Death mode-dependent reduction in succinate dehydrogenase activity in hair cells of aging rat cochleae

Background Our previous studies have shown that both apoptosis and necrosis are involved in hair cell (HC) pathogenesis in aging cochleae. To better understand the biological mechanisms responsible for the regulation of HC death, we examined the activity of succinate dehydrogenase (SDH), a mitochondrial bioenergetic enzyme, in the HCs of aging cochleae.Methods The auditory brainstem response thresholds elicited by tone bursts at 4, 10 and 20 kHz were measured in both young (2-3 months) and aging (22-23 months) Wistar rats. SDH activity was evaluated with a colorimetric assay using nitroblue tetrazolium monosodium salt. The SDH-labeled organs of Corti were double stained with propidium iodide, a DNA intercalating fluorescent probe for illustration of HC nuclei. All the specimens were examined with fluorescence microscopy and confocal microscopy.Results Aging rats exhibited a significant elevation of ABR thresholds with threshold shifts being 34 dB at 20 kHz, 28 dB at 10 kHz, and 25 dB at 4 kHz. Consistent with the reduction in the cochlear function, aging cochleae exhibited the reduction of SDH staining intensity in the apical and the basal ends of the cochleae, where a large number of apoptotic, necrotic, and missing HCs were evident. The reduction in SDH staining appeared in a cell-death-mode dependent fashion. Specifically, SDH labeling remained in apoptotic HCs. In contrast, SDH staining was markedly reduced or absent in necrotic HCs.Conclusions In the aging cochlea, SDH activity is preserved in HCs undergoing apoptosis, but is substantially reduced in necrosis. These results suggest that mitochondrial energetic function is involved in the regulation of cell death pathways in the pathogenesis of aging cochleae.     

Death mode-dependent reduction in succinate dehydrogenase activity in hair cells of aging rat cochleae

Background Our previous studies have shown that both apoptosis and necrosis are involved in hair cell （HC） pathogenesis in aging cochleae. To better understand the biological mechanisms responsible for the regulation of HC death, we examined the activity of succinate dehydregenase （SDH）, a mitochondrial bioenergetic enzyme, in the HCs of aging cochleae. Methods The auditory brainstem response thresholds elicited by tone bursts at 4, 10 and 20 kHz were measured in both young （2-3 months） and aging （22-23 months） Wistar rats. SDH activity was evaluated with a colorimetric assay using nitroblue tetrazolium monosodium salt. The SDH-labeled organs of Corti were double stained with propidium iodide, a DNA intercalating fluorescent probe for illustration of HC nuclei. All the specimens were examined with fluorescence microscopy and confocal microscopy. Results Aging rats exhibited a significant elevation of ABR thresholds with threshold shifts being 34 dB at 20 kHz, 28 dB at 10 kHz, and 25 dB at 4 kHz. Consistent with the reduction in the cochlear function, aging cochleae exhibited the reduction of SDH staining intensity in the apical and the basal ends of the cochleae, where a large number of apoptotic, necrotic, and missing HCs were evident. The reduction in SDH staining appeared in a cell-death-mode dependent fashion. Specifically, SDH labeling remained in apoptotic HCs. In contrast, SDH staining was markedly reduced or absent in necrotic HCs. Conclusions In the aging cochlea, SDH activity is preserved in HCs undergoing apoptosis, but is substantially reduced in necrosis. These results sUggest that mitochondrial energetic function is involved in the regulation of cell death pathways in the pathogenesis of aging cochleae.     

Death mode-dependent reduction in succinate dehydrogenase activity in hair cells of aging rat cochleae

Background Our previous studies have shown that both apoptosis and necrosis are involved in hair cell (HC) pathogenesis in aging cochleae. To better understand the biological mechanisms responsible for the regulation of HC death, we examined the activity of succinate dehydrogenase (SDH), a mitochondrial bioenergetic enzyme, in the HCs of aging cochleae.Methods The auditory brainstem response thresholds elicited by tone bursts at 4, 10 and 20 kHz were measured in both young (2-3 months) and aging (22-23 months) Wistar rats. SDH activity was evaluated with a colorimetric assay using nitroblue tetrazolium monosodium salt. The SDH-labeled organs of Corti were double stained with propidium iodide, a DNA intercalating fluorescent probe for illustration of HC nuclei. All the specimens were examined with fluorescence microscopy and confocal microscopy.Results Aging rats exhibited a significant elevation of ABR thresholds with threshold shifts being 34 dB at 20 kHz, 28 dB at 10 kHz, and 25 dB at 4 kHz. Consistent with the reduction in the cochlear function, aging cochleae exhibited the reduction of SDH staining intensity in the apical and the basal ends of the cochleae, where a large number of apoptotic, necrotic, and missing HCs were evident. The reduction in SDH staining appeared in a cell-death-mode dependent fashion. Specifically, SDH labeling remained in apoptotic HCs. In contrast, SDH staining was markedly reduced or absent in necrotic HCs.Conclusions In the aging cochlea, SDH activity is preserved in HCs undergoing apoptosis, but is substantially reduced in necrosis. These results suggest that mitochondrial energetic function is involved in the regulation of cell death pathways in the pathogenesis of aging cochleae.     

Joseph病黄氏家系患者腓肠肌活检的组织化学观察

本文报导1例Ⅲ型Joseph病黄氏家系患者腓肠肌活检的组织化学观察结果,表明NADH—TR反应增强,而SDH反应减弱,提示线粒体的酶反应出现异常,另外在蒌缩的肌纤维内还多见脂褐素颗粒沉集,揭示本例为一神经原性疾患。