3-硝基丙酸的神经毒理

３－硝基丙酸的神经毒理何凤生付以同（中国预防医学科学院劳动卫生与职业病研究所，北京１０００５０）３－硝基丙酸（３－ＮＰＡ）是引致我国北方流行的变质甘蔗中毒的一种霉菌毒素．儿童吃后数小时内即可引起急性非炎性脑病，出现抽搐与昏迷；重者还可留有迟发性肌张力...     

正常大鼠、高血压大鼠局灶性脑缺血损伤及 764-3 的保护作用

目的：观察丹参有效成分７６４－３对正常大鼠和高血压大鼠脑缺血损伤的保护作用。方法：分别阻断正常大鼠和肾性高血压大鼠一侧大脑中动脉，观察缺血２４ｈ其脑比重、脑血管通透性、脂质过氧化代谢产物——丙二醛等脑损伤指标的改变，以及丹参有效成分７６４－３对这种改变的作用。结果：正常大鼠脑局灶性缺血２４ｈ后，皮层、尾核、海马的比重降低，形成了脑水肿，脑血管通透性、脑丙二醛的含量也明显增加，丹参有效成分７６４－３对这种改变有明显抑制作用。高血压大鼠仅杏仁核形成水肿，其脑血管通透性、脑丙二醛的含量明显增加，７６４－３对脑丙二醛增加和脑水肿的形成有明显抑制作用，对血管通透性的增加无抑制作用。结论：丹参有效成分７６４－３对脑缺血具有保护作用。     

3－硝基－1，2，4－三唑类乏氧细胞放射增敏剂的构效关系

为了寻找毒性低、增敏作用强的乏氧细胞放射增敏剂，设计并合成了一系列５－溴－，５－甲基－，和５－未取代的３－硝基－１，２，４－三唑－１－乙酰胺类化合物，用ＨｅＬａＳ３细胞进行了体外试验。结果表明５－溴取代衍生物的增敏作用强于相应的５－甲基－或５－未取代的硝基三唑衍生物，但是它们的毒性亦增大。修饰１位乙酰胺侧链也可以改变化合物的增敏作用和亲脂性。在所测定的化合物中ＴＡ－１０１［２－（３－硝基－１－三唑基）乙酰胺］由于有高的增敏作用和低亲脂性，可能是一个有希望的放射增敏剂。     

3-硝基丙酸预处理诱导沙土鼠脑缺血耐受与海马星形胶质细胞的激活

目的：探讨海马区星形胶质细胞的激活与3－硝基丙酸（3－NPA）预处理诱导脑缺血耐受的关系。方法：阻断沙土鼠双侧颈总动脉造成前脑缺血模型，通过HE染色和免疫组化观察海马锥体细胞死亡和星形胶质细胞的反应。结果：对照组海马CA1区已失去正常结构，锥体细胞大部分丧失，存活神经元计数显低于假手术组。3－NPA预处理组存活神经元减少，但高于对照组，假手术组海马CA1区仅见少量胶质原纤维酸性蛋白（GFAP）阳性细胞，染色较弱，突起不明显，对照组海马CA1区GFAP阳性细胞增多，多为弱阳性。3－NPA预处理组海马CA1区GFAP阳性细胞数目明显增多，染色较深，突起增粗。结论：星形胶质细胞形态和机能的改变可能与3－硝基丙酸预处理诱导脑缺血耐受有关。     

甲状旁腺素对人成骨肉瘤细胞株SaOS-2内cAMP,IP3,Ca~(2+)的作用研究

目的通过研究ｈＰＴＨ（１～３４）对人成骨肉瘤细胞株ＳａＯＳ－２胞浆内ｃＡＭＰ、ＩＰ３、Ｃａ２＋的影响，来阐明ＰＴＨ与其膜上特异受体结合后的胞浆内主要信息传递途径。方法利用蛋白竞争结合法测定胞浆内ｃＡＭＰ，以Ｆｌｕｏ－３／ＡＭ作为荧光指示剂，激光共聚焦显微系统显示ＳａＯＳ－２内［Ｃａ２＋］ｉ的变化，离子交换层析法测定ｈＰＴＨ（１～３４）作用下胞浆内ＩＰ３的改变。结果ｈＰＴＨ（１～３４）可使ＳａＯＳ－２胞浆内ｃＡＭＰ明显升高且与其浓度呈正相关，其最佳作用时间为１０ｍｉｎ。ｈＰＴＨ（１～３４）能迅速提高ＳａＯＳ－２内［Ｃａ２＋］ｉ，而且作用３０ｓ时ＳａＯＳ－２胞浆内ＩＰ３升高即达最高峰，未发现百日咳毒素对此现象有抑制作用。结论ｃＡＭＰ及ＩＰ３／Ｃａ２＋两条信息途径均参与ｈＰＴＨ（１～３４）对成骨细胞的调节作用     

甲状旁腺素对人成骨肉瘤细胞株SaOS—2内cAMP,IP3,Ca^2＋的作 …

目的 通过研究ｈＰＴＨ（１￣３４）对人成骨肉瘤细胞株ＳａＯＳ－２脑浆内ｃＡＭＰ、ＩＰ３、Ｃａ＾２＋的影响，来阐明ＰＴＨ与其膜上特异受体结合后的胞浆内主要信息传递途径。方法 利用蛋白竞争结合法测定胞浆内ｃＡＭＰ，以Ｆｌｕｏ－３／ＡＭ作为荧光指示剂，激光共聚焦显微系统显示ＳａＯ２－２内［Ｃａ＾２＋］ｉ的变化，离子交换层析法测定ｈＰＴＨ（１￣３４）作用下胞浆内ＩＰ３的改变。结果 ｈＰＴＨ（１￣３４）可使     

硝基咪唑N－烷基化的固液相转移催化法

硝基咪唑Ｎ－烷基化的固液相转移催化法ＬｉｕＺＺ等［ＳｙｎＣｏｍｍｕｎ，１９９３：２３．２６１１］２－甲基－４（５）－硝基咪唑与卤烷在Ｋ２ＣＯ３／ＴＢＡＢ／ＣＨ３ＣＮ固液相转移催化下生成１－烷基－２－甲基－４－硝基咪唑，１０例收率８４～９６％。该反应收...     

1,3—双[2—（3—氨基苯基）咪唑—1—基甲基]苯的合成

间硝苯甲腈与乙二胺进行缩合反应生成２－（３－硝基苯基）咪唑啉,继以活性二氧化锰氧化生成２－（３－硝基苯基）咪唑。该咪唑与间－二（溴甲基）苯进行烷基化反应生成１,３－双「２－（３－硝基苯基）咪唑－１－基甲基」苯,再以水合肼还原生成目标化合物。     

TxA_2/PGH_2受体拮抗剂——过敏性鼻炎治疗药 雷马曲班(ramatroban)

１ 商品名 Ｂａｙｎａｓ２ 化学名(Ｒ）－３－［［（４－氟苯）磺酰］氨基］－１，２，３，４－四氢化－９Ｈ－咔唑－９－丙酸３ 开发与上市厂商(德）Ｂａｙｅｒ公司研制，２００１年５月首次在日本上市。４ 适应证 适用于治疗过敏性鼻炎。５ 药理 血栓烷（Ｔｘ）Ａ２及其前体──前列腺素内过氧化物Ｈ２（ＰＧＨ２）均作用于同一受体，具有极强的血管、支气管平滑肌收缩作用和血小板活化作用。ＴｘＡ２主要在血小板中形成，但也可由其它细胞和组织如肺、多形核白细胞和人血管产生。据认为ＴｘＡ２是血栓性疾病，心、脑血管病和支气管哮喘的…     

大鼠缺血性周围神经病的实验模型制作

为探讨缺血性周围神经损伤的病理机制,采用结扎Wistar大鼠股动静脉建立坐骨神经缺血模型,将40只大鼠,随机分5组(假手术组和缺血1、2、3、4周组),采用坐骨神经功能指数(SFI)评价其功能状态,并观察病理改变。结果表明,大鼠的SFI第1天明显变坏,第2周最明显,第3周开始恢复。组织病理的最早改变为神经外膜下组织水肿,开始出现膨大、断裂的轴索;第2周水肿达高峰,轴索变性明显并出现髓鞘的脱失和吞噬细胞反应;第3、4周在神经的横断面上见到中心性有髓纤维丢失。结论:缺血性周围神经病的病理表现为神经外膜下水肿,轴索变性,继之出现髓鞘脱失。中心性有髓纤维的丢失,提示分水岭性神经损害。     

Investigation of the renal injury caused by liver ischemia-reperfusion in rats

To explain the mechanism of renal injury caused by liver ischemia-reperfusion, we investigated biochemical and morphological changes in the liver and kidney in rats. After reperfusion following 60 min of liver ischemia, numerous changes were found. The level of serum transaminases and lipid peroxide formation in the liver tissue increased significantly. Electron microscopic studies revealed that most of the hepatocytes had swollen mitochondria and clumping of the nuclear chromatin. The sinusoidal endothelium was disrupted and the sinusoidal lumen was filled with numerous erythrocytes. Blood endotoxin concentration, plasma lipid peroxide levels, and serum -glucuronidase activities were significantly higher than in the control group. Biochemical and morphological renal injury was also observed. Tissue lipid peroxide levels increased in both the kidney and the liver. Microscopic examination revealed damage to the renal tubules, including interstitial edema, dilatation of the lumen, and granular casts derived from necrotic cells in the proximal convoluted tubule. The levels of urinary N-acetyl--d-glucosaminidase (NAG) in the liver ischemia-reperfusion group were also higher than in the control group. These results suggest that the renal injury was caused by an increase in endotoxin, lipid peroxide, and lysosomal enzymes in the blood following the liver injury induced by the ischemia-reperfusion.     

Isoproterenol-induced ultrastructural alterations in hearts of alloxan-diabetic rabbits

1. The effects of isoproterenol (ISO) on the ultrastructure of hearts from 10-week alloxan diabetic rabbits were examined. 2. Following alloxan injection, all rabbits developed severe hyperglycemia, hyperlipidemia and hypoinsulinemia. 3. Injection of ISO induced marked alterations in both control and diabetic rabbit hearts including accumulation of lipid and swelling of sarcoplasmic reticulum. 4. Myofibrils in both groups of animals were dispersed and appeared as a homogeneous mass with poorly defined Z-bands. 5. The most marked effect of ISO treatment in both groups of animals was damage to mitochondria. Mitochondria were extensively damaged and showed partial or complete disruption of their cristae network. 6. Glycogen granules were few in number or not detectable in both groups of animals. 7. The diabetic animals treated with ISO showed greater clumping and margination of nuclear chromatin, fewer intact mitochondria and a greater number of amorphous dense bodies in and around the mitochondria. 8. The presence of greater sarcolemmal damage in diabetic animals was inferred from the significantly greater accumulation of calcium and decreased magnesium in the myocardium.     

A Fine Structural Study of Liver (Littoral) Cells of Methylmercury Fed Japanese Quail (Coturnix coturnix japonica)

Abstract Tissues of Japanese quails were subjected to electron microscopical study. The birds had received 0–8 ppm methylmercury added to their diets for 6 weeks. The ultrastructural changes in the littoral cells of the liver were swollen mitochondria, with dilatation of the endoplasmic reticulum, loss of ribosomes from the rough endoplasmic reticulum and an increase in the number of vesicles in the cytoplasm. The nuclear membrane in some littoral cells became dilated, and the nuclear chromatin was condensed. The physiological effect of the destruction of the littoral cells is discussed.     

诊断用彩色多普勒超声辐照对小鼠早孕胚胎细胞超微结构的影响

目的:应用彩色多普勒超声辐照早孕小鼠胚胎,观察小鼠早孕胚胎细胞超微结构的变化。方法:8只孕6~7 d成年昆明种小鼠,按彩超辐照时间不同随机等分为4组,组(对照组)、组(辐照10 min组)、组(辐照20 min组)、组(辐照30 min组),仪器采用百胜公司DU-8型彩色超声诊断仪。照射条件:腹部凸阵探头,探头频率为3.0MHz,MI=0.9 TiS=0.9。照射后24 h取小鼠胚胎标本,HE染色光镜观察组织结构,透射电镜观察超微结构变化。结果:各组光镜下观察胚胎组织结构均未见异常。照射30 min组小鼠胚胎细胞电镜检查发现染色质浓缩边集、线粒体肿胀等超微结构变化。结论:彩色多普勒超声辐照早孕小鼠可引起胚胎细胞超微结构发生改变。     

Sweat gland toxicity induced by bis (tributyltin) oxide: an ultrastructural and X-ray microanalysis study

Acute toxicity of bis (tributyltin) oxide in the sweat glands in the rat footpad was investigated by electron microscopy and an energy-dispersive X-ray microanalyzer. Male Wistar rats received an intramuscular injection of 0.5 ml/kg bis (tributyltin) oxide. After 6-8 h, swelling of mitochondria appeared in the secretory cells of the sweat glands. After 12 h, the secretory cells began to show intracytoplasmic edema. After 16-20 h, secretory cells in some sweat glands showed marked hydropic degeneration with swollen cytoplasm. Using X-ray microanalysis, tin peaks were preferentially obtained from the swollen mitochondria of the affected secretory cells. Mitochondria dysfunction due to the toxic effects of bis (tributyltin) oxide induced changes in the secretory cells of rat sweat glands. After 24-48 h, the secretory portion of the sweat glands contained three types of cells: degenerating dark cells, regenerating cells carrying injured mitochondria, and light cells which were morphologically very similar to the cells in the transitional portion of the sweat gland. These light cells appeared to differentiate into active secretory cells after settling down in the secretory portion. Based on these observations, we concluded that the cells in the transitional portion could play an important role at least as reserve cells against secretory cell toxicity. In association with the regenerating process of the damaged secretory portions, increased mitotic activities were seen in different areas of all the dermal sweat ducts. The above-mentioned morphological observations for cell damage and subsequent regeneration and renewal ofsecretory cells in sweat gland intoxication have not been reported so far.     

3-硝基丙酸对沙土鼠海马CA1区锥体细胞超微结构的影响

目的观察小剂量3-硝基丙酸(≤20mg/kg)对沙土鼠海马CA1区锥体细胞超微结构的影响.方法将沙土鼠腹腔注射不同剂量3-硝基丙酸或双蒸水后3d,取海马CA1 区用戊二醛和锇酸固定,电镜下观察CA1区锥体细胞层神经元细胞核和细胞器超微结构形态变化,用体视学方法计算每张照片线粒体和粗面内质网体面积变化.结果实验组与对照组比较细胞核无明显变化,线粒体和粗面内质网轻度肿胀,体密度高于对照组.结论小剂量3-硝基丙酸可引起神经元缺氧代偿性反应,无致死性损害.     

Duodenal mucosal response to the pungent principle of hot pepper (capsaicin) in the rat: Light and electron microscopic study

Light and electron microscopic investigations were undertaken on adult rats in order to clarify the immediate effect of capsaicin on duodenal absorptive cells following intraduodenal and intragastric administration. Both natural and synthetic capsaicin administered by the same route for the same length of time produced identical morphologic alterations. Injury increased with duration of exposure, and within 2 min mitochondria were swollen with rarefied matrix and disorganized cristae. Increased numbers of free ribosomes and lysosomes and dilatation of endoplasmic reticulum and Golgi complexes were evident. Nuclei were shrunken and chromatin was clumped and marginated at the nuclear envelope. The consequences of these cellular alterations, as they relate to the function and physiology of the absorptive cell, are under investigation.     

大鼠脑心综合征模型的建立

目的建立大鼠脑心综合征模型。方法采用线栓法栓塞大鼠右侧大脑中动脉,连续监测大鼠标准II导联心电图,观察记录心律失常出现情况;大鼠右侧大脑中动脉栓塞后30min、2h、24h及缺血2h再灌6h分别取左心室心肌,透射电镜观察心肌细胞受损程度;TTC染色测定脑梗死率。结果大鼠右侧大脑中动脉栓塞后(14.9±11.4)min内0.71大鼠出现室性早搏(0.38)、房性早搏(0.27)、室性心动过速(0.05)、窦性心动过速(0.01)等心律失常,心律失常持续时间为(29.0±23.2)min。电镜下见心肌细胞有明显损伤:线粒体嵴紊乱、断裂,细胞核膜下染色质聚集,胞质内糖原颗粒沉着等。脑组织TTC染色结果显示,大鼠右侧大脑中动脉栓塞后30min、2h、24h脑梗死率分别达到0.087±0.011、0.114±0.023和0.137±0.031。结论采用线栓法栓塞大鼠右侧大脑中动脉,能制得稳定的脑心综合征模型;大鼠右侧大脑中动脉栓塞引起的心律失常是脑缺血致心肌组织的病理损害所致。     

Corneal edema induced by bis (tributyltin) oxide

Comeal edema induced by bis (tributyltin) oxide (TBTO) was studied with an electron microscope and the accumulation sites of tin were determined with an X-ray microanalyzer. Male Wistar rats received an intramuscular injection of 0.5 ml/kg TBTO. After time intervals of 2,4, 6, 8, 10, 12 h after injection, corneas were isolated and provided for electron microscopy. Corneas from untreated rats served as controls. Marked swelling of mitochondria in the corneal endothelial cells occurred at 4 h after TBTO injection. The corneal edema appeared in the endothelial layer and the stroma at 6 h after injection. By X-ray microanalysis, Sn peaks were obtained from swollen mitochondria in the endothelial cells. At 12 h after TBTO injection, edematous swelling of the corneal tissue became more advanced. These results indicated that parenterally administered TBTO accumulated in the mitochondria of corneal endothelial cells. The direct toxic effects of TBTO on the mitochondria might cause the interference with active pump function of endothelial cells and induced the corneal edema.     

急性压力超负荷后大鼠心肌损伤与血管紧张素Ⅱ的关系

观察大鼠腹主动脉狭窄后心肌形态学动态变化及其与心肌血管紧张素Ⅱ（ＡｎｇⅡ）含量的关系． 结果表明腹主动脉狭窄形成急性压力超负荷后,大鼠心肌出现明显的缺氧性损伤,线粒体数密度减小,肿胀变性,心肌中ＡｎｇⅡ含量迅速升高,一氧化氮（ＮＯ）含量迅速降低． 卡托普利（３０ ｍ ｇ·ｋｇ－ １·ｄ－ １,术前ｐｏ ２ ｄ）可明显抑制急性压力超负荷引起的心肌中ＡｎｇⅡ含量升高和ＮＯ 含量降低,减轻心肌缺氧性损伤． 提示急性压力超负荷所致心肌缺氧性损伤可能与心肌血管紧张素系统活化有关．