三硝基甲苯(TNT)对大鼠毒作用的实验研究

本文报道了TNT对大鼠毒作用所引起主要脏器的病理改变和某些生化指标的变化.对肝组织作了电镜观察.染毒早期可见肝内质网扩张.亚急性中毒肝线粒体变性和内质网扩张成小泡状.光镜检查见肝细胞浊肿、嗜酸变和嗜酸小体形成.生化指标测定中,LDH_1和LDH_2升高,提示TNT除作用于肝脏外,可能对心肌亦有作用.200mg/kg染毒一周,大鼠睾丸即出现明显的病理改变,因此,睾丸对TNT也是敏感的器官之一.     

3-硝基-1,2,4-三唑-5-酮染毒大鼠病理学观察

探讨新型含能材料3-硝基-1,2,4-三唑-5-酮(NTO)对大鼠主要脏器的亚慢性毒作用。将NTO以食用植物油为溶剂分为0、250、500、1000 mg/kg剂量组给大鼠经口灌胃。染毒90 d,每周5 d,每天1次。染毒结束处死大鼠,取心、肝、脾、肺、肾、脑、睾丸、子宫观察其病理改变。结果显示,NTO染毒大鼠病理改变为肝细胞水肿、肝窦充血、炎细胞浸润、中央静脉扩张、点状坏死;肾脏病变表现为小球系膜细胞增生、近端小管水肿、炎细胞浸润、细部小管细胞增生纤维化;睾丸曲细精管变细,间隙较大,仅可见基底膜单层细胞,未见向管腔内分化的初级精母细胞、次级精母细胞、精子细胞及精子,间质水肿。250、500、1000 mg/kg剂量组睾丸系数低于对照组。提示NTO对大鼠的肝脏、肾脏、睾丸有一定的毒作用。     

氯乙烯染毒大鼠代谢酶活性的动态变化和肝损伤

目的　研究氯乙烯 (VCM)染毒大鼠代谢酶活性和肝损伤生化指标的动态变化 ,以及大鼠肝脏的病理改变 ,探索血清、肝组织VCM代谢酶活性变化与肝脏损伤间的关系。方法　大鼠染毒 12周 ,分别在第 3、6、9和 12周处死动物 ,代谢酶活性测定采用分光光度法 ;肝功能生化指标用自动生化分析仪测定 ;光镜、电镜检测染毒大鼠肝组织病理改变。结果　VCM代谢酶ALDH、CYP2E1和GSTs活性随染毒时间和剂量的增加发生改变 ,差异具有统计学意义。ALP与血清ADH的活性呈负相关 (r=- 0 6 4 9) ;血清GSTs、ADH的活性分别与肝组织中GSTs、ADH活性呈正相关 (r- =0 4 39、0 5 0 8,P <0 0 5 )。结论　VCM致肝损伤程度可能与代谢酶活性有关 ,肝脏代谢酶变化是VCM引起机体损害的早期较敏感指标。     

4种血清酶在三硝基甲苯染毒致大鼠肝损伤中的变化及意义

[目的]观察三硝基甲苯(TNT)染毒致大鼠肝损伤时血清乳酸脱氢酶(LDH)、谷氨酸氨基移换酶(ALT)、天门冬酸氨基移换酶(AST)和碱性磷酸酶(ALP)的活力变化情况,并探讨其意义。[方法]以50、100和200mg/kg体重剂量的TNT对大鼠每天一次经口染毒,分别于染毒2、4、6和8周后处死,测定血和肝组织TNT代谢产物2,6-二硝基-4-氨基甲苯(DNAT)水平、血靛青绿(ICG)10min滞留率(ICG_(R10))和血清LDH、ALT、AST、ALP的变化情况。[结果]TNT染毒大鼠血和肝组织DNAT均比对照组有明显升高,TNT染毒剂量与大鼠血清或肝组织DNAT呈显著性相关(P<0.01),血清与肝组织DNAT呈显著性相关(P<0.01);各TNT染毒组大鼠血清ICG_(R10)明显高于对照组。TNT高剂量染毒组大鼠血清LDH、ALT、AST和ALP活力有所降低,其他剂量组与对照组相比未见显著性变化;血清或肝组织DNAT与血清LDH呈显著性负相关(P<0.05或0.01),与ALT、AST和ALP均负相关,但未见显著性(P>0.05)。[结论]血清LDH、ALT、AST和ALP指标对TNT染毒诱导的大鼠肝损伤的反应并不敏感,似与TNT代谢产物DNAT对血清4种酶活力可能具有的一定抑制作用有关。     

蔬果洗涤剂的亚慢性毒性研究

本文用蔬果洗涤剂 6 2 5、 12 5 0、 2 5 0 0 m g/ kg· d对大鼠连续经口染毒三个月 ,同时设阴性对照组。结果发现蔬果洗涤剂对动物体重、血液常规及生化等各项指标均无明显的损伤作用。病理组织学检查 ,各实验动物肝、肾未见毒性病理改变 ,但睾丸组织细胞则有明显的毒性改变 ,随剂量增加病变加重 ,精子畸形率中剂量组高于对照组 ,血清乳酸脱氢酶同功酶(L DHx)活性随剂量增加而显著升高。显示蔬果洗涤剂对睾丸细胞有明显损害作用 ,值得注意。     

三硝基甲苯对大鼠肝脏毒性的实验研究

三硝基甲苯(TNT)是常见工业毒物,而中毒性肝损害又是TNT毒作用的重要表现形式之一。对其中毒机理目前已有不少研究,它在肝脏中还原活化并进而引起的脂质过氧化与钙稳态紊乱可能在造成细胞损伤上有一定作用、本文就TNT急性和亚急性染毒和体外肝脏灌流时某些生化指标与形态学改变,进     

硫酸镍对体外培养大鼠睾丸间质细胞超微结构的影响

目的通过观察硫酸镍(NiSO4)对体外培养大鼠睾丸间质细胞超微结构的改变,初步探讨镍致睾丸间质细胞损伤的特点。方法采用胶原酶消化、Percoll分离液密度梯度离心和差速贴壁法体外分离、纯化睾丸间质细胞,采用3β-HSD染色法鉴定其纯度;采用MTT法观察NiSO4(浓度为0.0、62.5、125.0、250.0、500.0和1000.0μmol/L)染毒3、6和12h后,对睾丸间质细胞生长抑制的影响;采用透射电镜观察染毒6h后大鼠睾丸间质细胞超微结构的变化。结果纯化的睾丸间质细胞采用3β-HSD染色后,镜下可见睾丸间质细胞被染成蓝黑色,细胞纯度可达到95%以上;与对照组比较,染毒6h,NiSO4浓度为125.0μmol/L及其以上浓度组对间质细胞生长具有明显的抑制作用,差异有统计学意义(P<0.05或P<0.01);NiSO4可引起大鼠睾丸间质细胞线粒体和内质网超微结构改变,主要表现为线粒体肿胀,滑面内质网扩张及脱颗粒现象,溶酶体增多,尤其NiSO4浓度为500.0和1000.0μmol/L变化明显。结论 NiSO4可引起大鼠睾丸间质细胞超微结构改变。     

TNT影响肝脏混合功能氧化酶的规律

利用大鼠苯巴比妥诱导条件下急性和亚急性实验模型,以肝微粒体细胞色素P-450含量、氨基比林脱甲基酶活性、苯胺羟化酶活性和脂质过氧化水平为指标,进一步探讨不同剂量、不同时间TNT染毒对肝脏MFO影响规律及TNT改变MFO活性的可能机理。急性染毒时,各剂量组动物肝脏MFO功能均表现抑制,呈明显剂量反应关系;TNT对MFO抑制的酶谱较广,P-450含量、脱烷基功能和羟化功能均受影响。亚急性染毒见P-450含量与MFO代谢活性的改变同步,呈先诱导后抑制的双相效应,继而可表现“钝感”。TNT可在活体大鼠引起肝微粒体脂质过氧化,过氧化强度与MFO抑制程度经统计分析高度相关。本文扼要讨论了上述结果。     

太安染毒大鼠病理学观察

目的 研究太安对大鼠主要器官的毒作用。方法 用PETN以食用植物油为溶剂分为0,2．5,8．3,25mg／kg剂量组给大鼠灌胃,每日1次,每周6次,共90d。在45dg寸处死部分动物,其余染毒结束后处死,取其肝、肾、心、肺、脾脏、睾丸,观察其病理改变。结果 大鼠主要器官病理改变与对照组比较差异无显著件。结论 上述染毒条件下PETN未引起大鼠某些主要器官的病理改变。     

妊娠期二月桂酸二丁基锡暴露对子代雄性大鼠生殖系统的影响

目的探讨妊娠期二月桂酸二丁基锡(DBTD)暴露对子代雄性大鼠性成熟后生殖系统的影响及其作用机制。方法将16只健康SPF级妊娠Wistar大鼠随机分为4组,分别为溶剂对照(玉米油)组和低(10 mg/kg)、中(20 mg/kg)、高剂量(30 mg/kg)DBTD染毒组,每组4只。采用灌胃方式进行染毒,染毒容量为5 ml/kg,自妊娠第12～20天连续染毒。仔鼠出生后第70天,每组随机抽取10只雄性大鼠,称重后处死,测定睾丸和附睾重量及其脏器系数、附睾精子数以及血清中黄体生成素(LH)、卵泡刺激素(FSH)和睾酮(T)以及睾丸组织中睾酮(T)的水平,并观察睾丸组织病理学改变。结果各剂量DBTD染毒组子代雄性大鼠体重、附睾重量及其脏器系数、血清中LH和FSH水平与溶剂对照组相比,差异均无统计学意义。与溶剂对照组比较,高剂量DBTD染毒组子代雄性大鼠睾丸重量及其脏器系数,中、高剂量DBTD染毒组子代雄性大鼠附睾精子数较高,差异均有统计学意义(P0.05或P0.01)。且随着DBTD染毒剂量的升高,子代雄性大鼠睾丸重量及其脏器系数以及附睾精子数均呈升高趋势。与溶剂对照组比较,高剂量DBTD染毒组子代雄性大鼠血清T水平和各剂量DBTD染毒组子代雄性大鼠睾丸T水平均较高,差异有统计学意义(P0.05或P0.01)。结论在本实验染毒时间和剂量范围内,孕期DBTD染毒可干扰子代雄性大鼠体内T的合成和代谢,从而促进睾丸发育和精子形成。     

Copper-induced hepatic ultrastructural alterations in the snake-headed fish, Channa punctatus

Ultrastructural alterations in the liver of the snake-headed fish (Channa punctatus) following short-term exposure to 0.05 and 0.1 mg/liter of Cu were investigated by means of transmission electron microscopy. The changes consisted of extensive proliferation of the smooth endoplasmic reticulum and dilation of the rough endoplasmic reticulum, suggesting an active detoxification attempt by the liver. Mitochondrial degenerative changes such as loss of normal material density, cristae, or outer or inner membranes with mitochondrial swelling were also observed after Cu intoxication. An increase in the numbers of lysosomes and electron dense bodies was examined. Granular chromatin and electron dense accumulation were observed in the nucleus at 0.05 mg/liter of Cu after 4 days of exposure. Cytoplasmic debris in the hepatocyte cells became a frequent finding after 7 days of 0.05 mg/liter Cu treatment. More prominent alterations in hepatocytes were recorded at 0.1 mg/liter of Cu after 4 and 7 days of exposure. A highly dilated endoplasmic reticulum and shortened and reduced mitochondria were the prominent features of acute Cu toxicity. Nuclei of the necrotic cells showed marked clumping of chromatin with the aggregation of interchromatin material at the center of the nucleus. In some hepatocytes, bilobed nuclei with dilated nuclear membranes were also observed. The nucleoplasm of many cells showed continuity with the cytoplasm due to loss of nuclear inner and outer membranes. A comparison of liver pathology with that of other fish species and mammals has been attempted. The relationship of these cellular changes with the possible mode of action of Cu at cellular and subcellular levels is discussed.     

Ultrastructural and histochemical observations regarding the ovarian follicles of the amago salmon (Oncorhynchus rhodurus)

Pre- and postovulatory ovarian follicles of the amago salmon were investigated with special consideration given to the steroid production site. In the preovulatory specimens, the special thecal cells contained abundant mitochondria and smooth endoplasmic reticulum, as in the case of other steroid-producing cells, while the granulosa cells developed rough endoplasmic reticulum like protein-secreting cells. Remarkably ultrastructural changes occurred in the granulosa and the special thecal cells during the oocyte maturation stage; dilation of rough endoplasmic reticulum in the former cell and further development of smooth endoplasmic reticulum in the latter one. Histochemical reactions of delta 5-3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity were only positive in the special thecal cells of the postovulatory follicles. These results strongly suggest that the special thecal cells are the major sites of estrogen precursor synthesis in the amago salmon ovary.     

Pathological changes in testes and liver of male albino rats after dermal exposure to DDVP insecticide.

Exposure of male albino rats to DDVP insecticide at sublethal dose of 30 mg/kg/day through dermal painting for a period of 90 days didn't show any intoxication symptoms or mortality. However, cytopathological changes in testicular and liver tissues were evident. There was a positive correlation between the degree of cellular damage and the period of insecticide administration. In general, damages were prominent in rats treated for 30 days or more. Histological examination of testes showed degenerative seminiferous tubules and fewer leydig cells. Hepatic cells were congested, atrophied and showed different stages of necrobiotic changes. This suggests a great care and caution for workers during different phases of DDVP insecticide handling.     

大剂量吡哆醇的睾丸毒性体内外效应的比较研究

目的：　探讨大剂量吡哆醇（ＰＮ）的大鼠睾丸的毒性及可能机制。方法：采用腹腔注射和Ｓｅｒｔｏｌｉ－ｇｅｒｍ 细胞共培养两种模式,观察睾丸及副性腺变化。结果：注射１５ 天３００ｍ ｇ 和６００ｍ ｇ 组睾丸及副性腺萎缩,光镜和电镜下见精子细胞脱落、精母细胞变性坏死、精子释放延迟和异形精子,Ｓｅｒｔｏｌｉ细胞肿胀、微管稀少,内质网异位和扩张等。注射３０ 天效应更为明显。体外实验显示ＰＮ剂量与生精细胞脱落显著相关,并与Ｓｅｒｔｏｌｉ细胞骨架的变化一致。结论：　吡哆醇可能主要通过损伤Ｓｅｒｔｏｌｉ细胞,引起睾丸结构和功能改变。     

高功率微波辐射致大鼠心和肝损伤形态学观察

目的探讨高功率微波(HPM)辐射对大鼠心肌和肝实质细胞超微结构的影响。方法成年Wistar大鼠36只,雌雄各半,随机分为空白对照组和微波辐射组,每组18只;辐照后1,7和14 d处死大鼠,冰浴下立即取心肌心尖部、肝右叶组织,制作常规透射电镜标本并观察。结果高功率微波辐射后1,7 d时大鼠心肌细胞线粒体溶解空化,肌丝溶解、断裂;高功率微波辐射后最初大鼠肝细胞核内异染色质增多,部分线粒体嵴模糊,辐射后7 d部分线粒体肿胀;高功率微波辐射后14 d大鼠心肌细胞和肝细胞线粒体无明显肿胀,部分心肌肌丝仍有溶解、断裂,少数肝细胞胞质内有脂滴等。结论高功率微波辐射对大鼠心肌和肝实质细胞有明确的损伤效应,高功率微波辐射致大鼠心肌细胞损伤较重,并且损伤的心肌恢复较慢。     

Lower Respiratory Illness Among Alaskan Eskimo Children

The effects on mouse and monkey liver of long-term oral administration of chlorobiphenyls (CBP), 1.5 mg/day or more, have been investigated at selected intervals by light and electron microscopy. Hepatocytes of mice contained large amounts of acidophilic materials in the cytoplasm" and fatty vacuoles were observed later. Fine structural changes in the hepatocytes consisted of a marked increase of smooth endoplasmic reticulum, a reduction of rough endoplasmic reticulum, "myelin figure" formation in the cyto-plasm, and increase of microbodies and Iysosomes. A marked increase in lipid droplets was observed later. Results of electron microscopy in monkey liver showed an increase of smooth en" doplasmic reticulum in the hepatocytes and swelling of Kupffer’s cells, with an increased number of Iysosomes and vacuoles. Judging from the findings by electron microscopy, characteristic lesions of liver cells were produced by administration of CBP.     

三硝基甲苯对大鼠睾丸某些生化功能的影响

本研究采用急性染毒方式，观察三硝基甲苯（ＴＮＴ）对大鼠睾丸某些生化功能的影响。结果表明，２０００ｍｇ／ｋｇＴＮＴ染毒组睾丸葡萄糖－６－磷酸脱氢酶（Ｇ－６－ＰＤ）、乳酸脱氢酶（ＬＤＨ）、山梨醇脱氢酶（ＳＤＨ）和酸性磷酸酶（ＡＣＰ）活性下降，睾丸锌含量下降，而血清锌含量上升。１０００ｍｇ／ｋｇＴＮＴ染毒组睾丸Ｇ－６－ＰＤ和ＡＣＰ活性也下降，而血清锌含量升高。表明睾丸中Ｇ－６－ＰＤ和ＡＣＰ活性以及血清锌含量变化较为敏感。     

吴茱萸醇提物重复给药的靶器官毒性研究

摘要:目的　连续28 d对SD大鼠经口给予吴茱萸Evodia rutaecarpa（Juss）Benth醇提物,观察可能的毒性反应性质、程度及可逆性,判断毒性靶器官。方法　雌雄各半80只SD大鼠随机分4组,每组20只,分别给予20.83、6.66、2.50 g生药/kg· d吴茱萸醇提物和生理盐水,1次/d,连续28 d。给药结束、恢复14 d后各组解剖10只。解剖时称重脏器,腹主动脉采血进行血常规、生化检测,组织器官进行光镜、电镜检查。结果　（1）肝脏:给药动物肝肥大,无光泽,质脆;给药组肝脑比呈剂量依赖性改变,停药14 d后恢复;光镜下高剂量组肝细胞变性肿胀、炎细胞浸润（8/8）,病变分级高于对照组（P＜0.0083）,恢复期缓解;电镜下高剂量组肝细胞线粒体肿胀、内质网扩张,肝血窦内皮细胞有空泡,恢复期缓解。（2）血液系统:高剂量组红细胞及血红蛋白降低,有贫血征象,同时网织红细胞代偿性升高,恢复期未完全恢复。（3）心脏:电镜检查高剂量组心肌细胞肌丝紊乱、内质网扩张、线粒体肿胀,恢复期未好转,中低剂量组无明显异常,但恢复期加重。（4）肾脏:电镜检查高剂量组肾足细胞肿胀,肾小球系膜弯曲及肾小球血管内皮细胞肿胀,恢复期好转。结论　肝、血液系统为吴茱萸醇提物明确毒性靶器官;电镜检查心脏和肾脏有损伤,为可疑毒性靶器官。     

Ultrastructural changes in the liver after chronic exposure to methylmercury.

Adult male rats were injected daily with 1.0 mg/kg methylmercuric chloride for 5 weeks. Tissue samples from the liver were obtained at time intervals of 1, 2, 3, 4, 5, and 11 weeks for electron microscopic examination. A moderate accumulation of glycogen and proliferation of smooth endoplasmic reticulum was found in many hepatocytes after 1–2 weeks of intoxication. Swelling, pleomorphic, and degenerative changes of the hepatic mitochondria could be observed after the second week of methylmercury administration. After 3–5 weeks of intoxication, increased peribiliary accumulation of lysosomes, and large areas of focal cytoplasmic degradation were prominent pathological findings. Moderate accumulation of lipoprotein granules within dilated cisternae of the smooth endoplasmic reticulum and Golgi vesicle was observed in some hepatocytes after 5 weeks of continuous exposure to methylmercury. Large cytosegresomes containing various degenerating organelles were a frequent observation throughout the experimental period. Many of these cytosegresomes were being extruded into the sinusoidal spaces and engulfed by the Kupffer cells. At the eleventh week (6 weeks of recovery), various degenerative changes still could be found in some hepatocytes. Such long-lasting pathological changes in the liver are believed to be due to the effects of the residual and the recirculating mercury.