碘剂及心得安对Graves病患者甲状腺影响的透射电镜研究

用碘剂及心得安分别对Ｇｒａｖｅｓ病患者的甲状腺超微结构的影响进行透射电镜研究．碘剂组甲状腺滤泡上皮细胞内出现大量空泡状结构，线粒体数量增多、体积增大，线粒体嵴短缺，并有髓样结构．内质网扩张，分泌颗粒电子密度高、大小不等、形态各异．心得安组线粒体数量增加，体积增大更明显，巨大线粒体多见，粗面内质网明显增多、扩张，分泌颗粒增多，电子密度低，呈圆形，上皮细胞基部或上皮细胞间有淋巴细胞浸润．因此，可推测碘剂对甲状腺功能有抑制作用．     

诊断用超声对早孕绒毛膜超微结构的近,远期影响

本文观察了诊断用超声辐照人官内胚胎绒毛膜引起的超微结构改变。将４６例早孕妇女分五组：Ｉ组，未经超声辐照；Ⅱ组、Ⅲ组，分别Ｂ超、彩超辐照３０分钟于２４±ｌ小时行人流术；Ⅳ组、Ｖ组，分别Ｂ超、彩超辐照３０分钟于７２±ｌ小时行人流术。结果：Ⅱ、Ⅲ组细胞，合体滋养层均见细胞核周间隙增大，粗面内质网扩张，胞质空泡化。表明超声辐照后，质膜和亚细胞器是受损的主要部位，上述改变于辐照３天后（７２小时）在一定程度上可以恢复。     

肝素加运动治疗稳定型心绞痛疗效探讨

为探讨肝素在冠心病治疗中的作用，将２０例冠心病患者分两组进行比较分析。Ａ组：肝素加运动，共１０例患者，按标准方法进行２０次踏车运动试验，每次踏车运动前２０分钟静脉注射肝素钠５０００Ｕ；Ｂ组：单独肝素组，共１０例患者，进行皮下注射１０次，每次肝素钠１００００Ｕ，试验期间不做运动试验。全部患者在第１次应用肝素前２４小时和最后１次应用肝素后２４小时均行症状限制性踏车运动试验。在Ａ组，运动总时间从７．１３±０．８９分钟（ｘ±ｓｘ，下同）增加到１１．６７±１．０４分钟（Ｐ＜０．００１），最大血压心率乘积从２４０４．００±３１２．００ｋＰａ／ｍｉｎ增加到３１８２．００±４９５．００ｋＰａ／ｍｉｎ（Ｐ＜０．００１），而Ｂ组上述参数无明显改变。结论：肝素配合运动能够加速侧枝循环的建立，而单独应用肝素则无此作用。运动诱发心肌缺血可始动肝素再生血管的作用。本试验为冠心病的治疗提供了又一新的、有效的、实用的治疗方法     

高血糖对非酒精性脂肪性肝炎大鼠肝脏超微结构及细胞凋亡的影响

目的探讨高血糖对非酒精性脂肪性肝炎(NAFLD)大鼠肝脏超微结构及细胞凋亡的影响。方法将58只SPF级雄性大鼠采用随机数字表法分为正常组(n=10)、高血糖模型组(n=12)、复合模型组(高血糖合并NAFLD,n=12)、氨基胍组(n=12)、格列美脲组(n=12),检测各组血糖值,在电镜下观察肝脏超微结构,应用TUNEL染色法观察肝细胞凋亡情况,以酶联免疫吸附试验测定血浆基质金属蛋白酶抑制因子-1(TIMP-1)、转化生长因子β1(TGF-β1)、晚期糖基化终产物(AGEs)水平。结果氨基胍组、格列美脲组大鼠血糖值低于高血糖模型组、复合模型组(P0.05),且氨基胍组血糖值高于正常组(P0.05),格列美脲组血糖值与正常组比较,差异无统计学意义(P0.05)。与正常组比较,高血糖模型组、复合模型组肝组织出现细胞超微结构改变,核周围存在脂滴,且肝细胞浆中线粒体、内质网变形;而与复合模型组比较,格列美脲组肝细胞超微结构较正常,可观察到核周围脂滴分布明显改善,线粒体及内质网形态趋于正常,而氨基胍组核周围脂滴分布、线粒体与内质网形态有所改善。肝细胞凋亡率大小:复合模型组高血糖模型组正常组,复合模型组、高血糖模型组格列美脲组(P0.05)。各组血浆TIMP-1、TGF-β1、AGEs水平排序均为:复合模型组高血糖模型组正常组,复合模型组氨基胍组、格列美脲组(P0.05)。结论高血糖可能会促进NAFLD大鼠肝纤维化、肝脏超微结构改变及肝细胞凋亡,降低血糖或减少TIMP-1、TGF-β1、AGEs,有助于减轻或抑制肝脏超微结构改变及肝细胞凋亡。     

妊娠及哺乳期金黄地鼠甲状旁腺的形态计量学研究

应用电镜技术超薄切片法，对妊娠及产后哺乳期金黄地鼠甲状分腺的结构进行了动态观察及形态学计量．与非妊娠对照组比较，妊娠５天甲状旁腺主细胞内高尔基复合体发育良好，其体积密度明显增加．妊娠１０天甲状旁腺主细胞内粗面内质网和脂滴的体积密度增加，妊娠１５天甲状旁腺主细胞内分泌颗粒的体积密度减少，脂滴增加．哺乳５天和１０天甲状旁腺主细胞的形态学与对照组基本相同。提示妊娠可影响金黄地鼠甲状旁腺的细胞活动．     

高能震波对家兔肝组织影响的超微细胞化学研究

目的为深入探讨高能震波对肝组织结构和功能的早期影响，给临床预防损伤提供依据。方法震波对肝脏定位作用后，取肝组织切超薄片，制备硝酸镧示踪和电镜酶细胞化学标本在透射电镜下观察。结果镧示踪标记法显示镧颗粒进入了细胞及线粒体内；毛细胆管紧密连接区也出现了致密的镧沉积，并与肝细胞间隙的镧沉积物相连，表明毛细胆管紧密连接已开放。酶细胞化学技术显示肝细胞线粒体琥珀酸脱氢酶（ＳＤＨ）和毛细胆管壁上的碱性磷酸酶（ＡＬＰ）活性明显减弱或消失，焦磷酸硫胺素酶（ＴＰＰａｓｅ）的活性及定位也发生了改变，ＴＰＰａｓｅ从损伤的高尔基复合体及溶酶体样小泡漏出进入胞浆，部分毛细胆管壁上的ＴＰＰａｓｅ反应物减少。肝细胞间隙和毛细胆管紧密连接区可见ＴＰＰａｓｅ反应物。超微结构观察显示线粒体肿胀破裂，粗面内质网扩张囊泡化和脱颗粒。结论高能震波可以损伤肝细胞的超微结构与功能。     

兔腰神经根慢性压迫和炎症刺激后背根神经节的形态学变化研究

目的 分别经光镜和电镜观察兔腰神经根经慢性压迫和炎症刺激后背根神经节(dorsalrootganglion，DRG)的形态学变化。方法 纯种新西兰大白兔20只，随机分为对照组(5只)和实验组(15只)，实验组又分为损伤后10d、30d和90d组。取兔尾部的自体髓核组织放入内径1．5mm、外径2．5mm、管壁带孔的硅胶管内，压迫左侧L，神经根，实验组各亚组分别于造模后10d、30d、90d取材，作光镜及电镜观察。结果 10d组中，经压迫和炎症刺激后神经根与DRG胞膜水肿，内膜间隙明显充血、水肿，大量炎性细胞浸润，出现变性、坏死及小胶质细胞“嗜神经”现象；DRG胞质内粗面内质网及线粒体等细胞器含量减少，粗面内质网核糖体脱落，线粒体肿胀；细胞核常染色质淡染且分布不均匀，核膜皱褶。30d组DRG胞膜稍增厚，节细胞染色不均，部分神经元出现变性、坏死，DRG溶酶体与滑面内质网含量增多，线粒体肿胀，嵴部分消失，核仁浓缩偏向一侧。90d组DRG胞膜明显增厚，节细胞内纤维样改变：溶酶体及滑面内质网含量增多，线粒体肿胀、嵴消失，核仁浓缩居中。结论 神经根慢性压迫和自体髓核刺激可导致神经组织出现水肿、炎性细胞浸润以及神经纤维增生等神经变性改变。     

P27基因转染对瘢痕成纤维细胞超微结构的影响

目的：观察P27基因转染对体外培养增生性瘢痕成纤维细胞超微结梅的影响，探讨P27基因抑制瘢痕的作用。 方法：实验于2001-06／2002-01在第四军医大学烧伤科实验室、第四军医大学电镜中心完成。pcDNA—p273真核表达质粒由第一作者构建，应用基因转染技术将所构建的pcDNA3-p27载体转染成纤维细胞，培养的增生性瘢痕成纤维细胞分为空白对照组（即未经转染的增生性瘢痕成纤维细胞）、转pcDNA3空载体组、转pcDNA3-P27组。获得稳定的P27表达后，用透射电镜观察成纤维细胞内细胞器形态和数量的变化。 结果：①空白对照组成纤维细胞核大而呈圆形，核仁明显，胞浆内具有较丰富的粗面内质网，较发达的高尔基复合体，较多的线粒体、微丝、微管，细胞表面微绒毛及突起较多。②转pcDNA3空载体组粗面内质网、线粒体较丰富。⑨转pcDNA3-P27组细胞胞浆内粗面内质网、线粒体、微丝、微管明显减少，大部分细胞出现染色体边聚，粗面内质网上的核糖体明显减少，部分细胞呈现凋亡，大部分细胞呈典型的生长抑制像。④P27明显抑制增生性瘢痕成纤维细胞的合成功能。 结论：P27可能通过抑制成纤维细胞的细胞合成、增殖功能来抑制瘢痕形成。     

CO2超声造影对鼠肝影响的观察

通过对１２只Ｓｐｒａｇｕｅ－Ｄａｗｌｅｙ大鼠进行经股动脉肝脏ＣＯ２超声造影，并 与对照组比较，结果显示ＣＯ２微泡进入肝脏后。血清谷丙转氨酶升与对照组相比无明显差异；病理切片显示ＣＯ２组中仅２个肝细胞灶性能脂肪变性；电镜仅显示ＣＯ２组肝细胞有脂滴存在，但无明显的细胞器改变。     

自发性高血压大鼠心房特殊颗粒超微结构的形态计量分析

目的：观察自发性高血压大鼠右心耳肌细胞心房特殊颗粒(ASG)的形态学变化。方法：实验动物分为两组，取每组动物右心耳，运用透射电镜观察ASG的形态并应用形态计量学方法进行定量分析。结果：成年自发性高血压大鼠的心肌细胞内，ASG数目增加，直径增大，高尔基复合体发达；线粒体肿胀，部分嵴溶解断裂，部分内质网扩张，糖原颗粒增多。结论：自发性高血压大鼠心房利钠肽(ANP)的合成和释放均增加。     

糖尿病患者心内膜下心肌的超微结构改变

通过对１１例糖尿病患者心内膜下心肌活检的超微结构研究，发现部分心肌细胞肌原纤维排列紊乱，甚至局部消失；胞浆内有脂褐素、糖原颗粒沉积及脂滴浸润；线粒体增生、变性，出现巨线粒体；横小管肥大，横小管内有絮状物沉积。７例不伴有半发症的糖尿病患者中有６例可见心肌间的毛细血管基膜增厚，其中３例的心肌间质出现轻度纤维化，本研究认为糖尿病者有心肌细胞代谢紊乱基础上形成的心肌微血管病变在糖尿病心肌病变中起主要作用。     

Influence of feeding schedule on 24-h rhythm of hepatotoxicity induced by acetaminophen in mice

The influence of feeding schedule on the chronopharmacological aspects of acetaminophen (APAP) was examined in mice housed under 12-h light/dark cycle (lights on from 7:00 AM to 7:00 PM) with food and water ad libitum feeding (ALF) or under repeated time-restricted feeding (feeding time between 9:00 AM and 5:00 PM) for 2 weeks before the experiment. For the ALF group, there was a significant 24-h rhythm of mortality after APAP (600 mg/kg i.p.) injection. Peak mortality was observed after APAP injection at 9:00 PM and 1:00 AM, and nadir mortality was observed after drug injection at 9:00 AM. Hepatotoxicity after APAP (300 mg/kg i.p.) injection at 9:00 PM was significantly more severe than that after drug injection at 9:00 AM. Immunohistochemical staining using anti-APAP antibody 2 h after APAP injection was detected in centrilobular hepatocytes after drug injection at 9:00 PM but not after drug injection at 9:00 AM. CYP2E1 activity and hepatic glutathione (GSH) levels in untreated mice showed significant 24-h rhythms associated with APAP toxicity rhythm. The reduction in hepatic GSH levels after APAP injection at 9:00 PM was greater than that after drug injection at 9:00 AM. On the other hand, manipulation of the feeding schedule modified APAP hepatotoxicity rhythmicity, CYP2E1 activity, and GSH levels in the liver. Manipulation of the feeding schedule and choosing the most appropriate time of the day for drug administration may help to achieve rational chronopharmacology of some drugs including APAP in specific experimental and clinical situations.     

THE IN VITRO DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES : IV. THE ULTRASTRUCTURE OF MACROPHAGE DIFFERENTIATION IN THE PERITONEAL CAVITY AND IN CULTURE

The structure of unstimulated mouse peritoneal phagocytes has been examined by electron microscopy and compared to cells obtained from the inflamed peritoneum and from cultures maintained in vitro. The unstimulated cell resembles the blood monocyte and contains a moderate amount of rough surfaced endoplasmic reticulum, a small but well defined Golgi apparatus and a few, small, electron-opaque granules in the cytoplasm. During in vitro cultivation there are marked changes in cell ultrastructure. Most prominent is the formation of large electron-opaque granules, some of which have a complex matrix containing both electron-opaque and lucent vesicles. In addition, there is an increase in size of the Golgi apparatus with the appearance of new lamellae and tiny, smooth surfaced vesicles. With continued cultivation, large lipid droplets are found in apposition to the rough endoplasmic reticulum. The formation and size of electron-opaque granules as well as the enlargement of the Golgi region is stimulated by high concentrations of serum in the medium. Cells obtained from the peritoneal cavity of lipopolysaccharide stimulated animals demonstrated changes in ultrastructure similar to those seen in cells cultured in vitro.     

似昼夜节律对小鼠视网膜电图的影响

目的:观察不同时间对昆明、BALB/C,C57BL/6J小鼠视网膜电图(electroretinography,ERG)的影响,探讨小鼠ERG的似昼夜节律改变。方法:将各品系小鼠分为6组,每组5只,分别在4:00～8:00,08:00～12:00,12:00～16:00,16:00～20:00,20:00～24:00,24:00～4:006个时间区间,按照国际临床视觉电生理标准化方案进行暗适应ERG(ScotERG),最大混合反应(MaxERG),明适应ERG(PhotoERG)记录。结果:各品系小鼠视网膜电图表现较为规律的节律性,在20:00～24:00区间其ERG的b波幅值最高,在4:00～8:00区间开始下降,在12:00～16:00区间b波幅值最低。明适应ERG的b波幅和暗适应b波幅值有相反的节律性。结论:不同品系小鼠视网膜光敏感性有较规律的节律性,可能和小鼠的活动规律有关,时间节律的影响能严重的影响小鼠视觉电生理检查的稳定性。     

Dosing time-dependent tolerance of catalepsy by repetitive administration of haloperidol in mice

To investigate the effect of repeated administration time on the development of tolerance, male ICR mice, housed under 12:12-h light/dark cycle (7:00 AM, lights on), were treated with haloperidol 4 mg/kg/day i.p. at 9:00 AM or 9:00 PM, the time nearly corresponding to the maximal or minimal catalepsy responses to a single dose, respectively, for 14 days and catalepsy responses were monitored at 1 h after administration each day. The findings indicated that, on day 1 to day 6, a greater development of tolerance was seen in the group of mice treated at 9:00 AM, and catalepsy behavior exhibited a significant difference between the two dosing times (P < 0.01). The study of D(2) receptor mRNA expression in mouse striatum revealed that the phase of D(2) receptor mRNA rhythm was similar to that of catalepsy response, with the maximum around mid-light and the minimum around mid-dark. After repeated administration, the increase in D(2) receptor mRNA levels in mice treated with haloperidol at 9:00 AM was higher than that of mice treated with haloperidol at 9:00 PM. In addition, from a [(3)H]spiperone binding study, the amount of binding site [(3)H]spiperone after repeated injection of haloperidol at 9:00 AM was greater than that after repeated injection at 9:00 PM. These findings demonstrate the importance of dosing time on the susceptibility to extrapyramidal effects and the relation of administration time to D(2) receptor change and tolerance.     

人外周血树突状细胞的超微结构及其细胞化学特征

目的　观察体外富集的人外周血树突状细胞（ｄｅｎｄｒｉｔｉｃ ｃｅｌｌｓ,ＤＣ） 的光镜形态学,细胞超微结构及细胞化学特征。方法　取健康人新鲜外周抗凝血,采用淋巴细胞分离液分离单个核细胞进行培养,经细胞因子（ｒｈＧＭＣＳＦ,ｒｈＩＬ４ ,ｒｈＴＮＦα） 联合刺激培养９～１２ 天,富集含ＤＣ的细胞群,光镜形态学分辨ＤＣ形态及含量,用抗人血ＤＣ表面特异单克隆抗体（ｍＡｂ Ⅻ） 确认ＤＣ的细胞化学特征。结果　体外培养富集的人外周血ＤＣ群的ＤＣ含量达７０ ％ ～８０ ％ 。透射电镜观察表明,细胞因子诱导的人外周血ＤＣ群可见到两类ＤＣ亚群：一类可能来自ＤＣ前体细胞,其细胞表面有大量不规则树枝状突起（ 粗细不等） ,细胞核不规则,核仁小,细胞化学染色［髓过氧化物酶（ＰＯＸ） 、非特异性酯酶（ＮＳＥ）］ 均为阴性;另一类是由单核细胞分化来的ＤＣ,细胞形态不规则,细胞表面粗糙,有大量皱褶及较粗大树枝状突起,胞核常呈现肾形或马蹄形,核内异染色质边集。结论　细胞因子诱导的人外周血ＤＣ群存在多相性。     

TREM2-dependent lipid droplet biogenesis in phagocytes is required for remyelination

Upon demyelinating injury, microglia orchestrate a regenerative response that promotes myelin repair, thereby restoring rapid signal propagation and protecting axons from further damage. Whereas the essential phagocytic function of microglia for remyelination is well known, the underlying metabolic pathways required for myelin debris clearance are poorly understood. Here, we show that cholesterol esterification in male mouse microglia/macrophages is a necessary adaptive response to myelin debris uptake and required for the generation of lipid droplets upon demyelinating injury. When lipid droplet biogenesis is defective, innate immune cells do not resolve, and the regenerative response fails. We found that triggering receptor expressed on myeloid cells 2 (TREM2)–deficient mice are unable to adapt to excess cholesterol exposure, form fewer lipid droplets, and build up endoplasmic reticulum (ER) stress. Alleviating ER stress in TREM2-deficient mice restores lipid droplet biogenesis and resolves the innate immune response. Thus, we conclude that TREM2-dependent formation of lipid droplets constitute a protective response required for remyelination to occur.     

Chronopharmacology of analgesic effect and its tolerance induced by morphine in mice

The influence of morphine dosing time on analgesic effect after acute or chronic treatment, recovery of analgesic effect after once developed tolerance, and their pharmacological mechanisms were investigated in ICR male mice under a 12-h light/dark cycle (light on from 7:00 AM to 7:00 PM). There was a significant 24-h rhythm in the latency of thermal response at 30 min after morphine injection. The analgesic effect was significantly greater at the dark phase than at the light phase. The rhythmic pattern resembled overall the rhythm occurring in the latency of thermal response under non-drugged state. The absolute value of morphine analgesic effect (the real time spent on the hot-plate) on days 1 and 2 after morphine daily injection was significantly larger after morphine injection at 9:00 PM than after saline injection at 9:00 PM or after morphine injection at 9:00 AM. The recovery from tolerance of analgesic effect was significantly faster at the dark phase than at the light phase. The time-dependent difference in the analgesic effect after chronic treatment or recovery from tolerance is closely related to that in the expression of mu-opioid receptor. The present study suggests that 24-h rhythm of morphine analgesic effect is consistent with 24-h rhythm of mu-opioid receptor expression.     

Deficient activity of dephosphophosphorylase kinase and accumulation of glycogen in the liver

Low activity of phosphorylase and increased concentration of glycogen were found in liver tissue from five children with asymptomatic hepatomegaly. In vitro activation of liver phosphorylase in these patients occurred at the rate of 10% or less of normal. Elimination of the defect by the addition of kinase that activates phosphorylase demonstrated the integrity of the phosphorylase enzyme and the deficient activity of dephophophosphorylase kinase.On the average, 60% of the phosphorylase enzyme of normal human liver was in the active form. Phosphorylase kinase of rabbit muscle activated phosphorylase of normal human liver to a final value that was significantly higher than the one obtained in the absence of muscle phosphorylase kinase.The ultrastructural examination of hepatic tissue from the five patients revealed increased amounts of glycogen. There was scarcity of endoplasmic reticulum. There was intercellular glycogen in continuity with the glycogen of the hepatocytes through breaks in their circumference. Lipid droplets with lucid areas in the form of needles and plates contained aggregates of glycogen. There were numerous lysosomes, some containing glycogen. Large vacuoles filled with glycogen and surrounded by a membrane were seen occasionally. The vacuoles might reflect the lysosomal pathway of glycogen degradation, since there was apparent fusion of such autophagic vacuoles with small vesicles resembling primary lysosomes.