硝酸羟胺急性、亚慢性染毒大鼠毒作用靶器官的研究

目的研究硝酸羟胺(hydroxylammonium nitrate,HAN)的急性毒性及亚慢性染毒大鼠后主要毒作用的靶器官。方法急性毒性实验中经腹腔对大鼠进行单次染毒,观察动物中毒症状,计算HAN的LD50和95%的可信限;亚慢性毒性实验中,分别以HAN 71、42、8 mg/kg不同剂量和生理盐水经腹腔染毒动物,连续染毒13周后脱颈椎处死3/4动物,剩余1/4动物停止染毒再饲养4周后同法处死,观察大鼠中毒症状和脏器的组织病理学改变,探讨HAN主要毒作用靶器官。结果HAN腹腔染毒大鼠的LD50为139.3 mg/kg,95%可信限为132.3~146.7 mg/kg。HAN亚慢性染毒后,动物体重无明显变化,各染毒组动物脾脏脏器系数明显高于对照组(P<0.05);组织病理学检查表明,HAN可引起含铁血黄素在体内的大量沉积,主要位于肝、脾和肾内,对组织脏器的损伤主要以氧化性损伤为主,主要靶器官为肺、肝、脾和肾。结论HAN属于中等毒性物质,长期接触对机体有一定的毒性作用。     

石油沥青染毒大鼠亚慢性毒性实验研究

石油沥青是石油原油分馏后剩余的副产品。由于沥青具有防腐防水绝缘等特性 ,因此应用广泛。有关石油沥青烟吸入毒性的实验国内报道较少。现将石油沥青烟亚慢性吸入毒性的实验研究结果 ,报告如下。1　材料与方法实验用石油沥青由某石油化工厂提供 ;健康成年Ｗｉｓｔａｒ大鼠 6 0只 ,雌雄各半 ,体重为 130～ 140ｇ ,由黑龙江省中医学院实验动物中心提供。经过筛选 ,确定 42只大鼠为本组实验动物。实验分 3组 ,每组 14只 ,高浓度组石油沥青烟浓度为 32 0～ 410ｍｇ ｍ3(平均为 35 0ｍｇ ｍ3) ,低浓度组为 10 0～ 15 0ｍｇ ｍ3(平均为 12 0ｍｇ …     

环氧乙烷对大鼠肝脏毒性作用的实验研究

环氧乙烷对大鼠肝脏毒性作用的实验研究＊钟先玖周元陵范卫以组织病理学改变及血清酶活性变化作为观察指标，研究了环氧乙烷（ＥｔＯ）肝脏毒性作用。材料与方法一、材料１．ＥｔＯ购自杭州电化厂，纯度大于９９％。２．ｗｉｓｔａｒ大鼠，由中国科学院上海实验动物中心提...     

氯化镍对大鼠肝脏毒性实验

氯化镍对大鼠肝脏毒性实验周晓，甘卉芳，刚葆琪镍的肝脏毒性近年国外亦见零星报道，Ｄｏｎｓｋｏｙ等的研究表明，镍对大鼠可致急性和亚急性肝脏损伤［１，２］，为探讨相对较低剂量下镍对肝脏毒作用特点，进行了此项实验。材料与方法受试物为氯化镍（ＮｉＣｌ２·６Ｈ２...     

氢氧化镧对大鼠慢性肾衰高磷血症的改善作用研究

目的:研究氢氧化镧对大鼠慢性肾衰高磷血症的改善作用。方法:取大鼠建立慢性肾衰高磷血症模型,再随机分为模型组、碳酸镧组[0.3 g/(kg·d)]、碳酸钙组[4.2 g/(kg·d)]和氢氧化镧高、中、低剂量组[1.5、1、0.5 g/(kg·d)],每组10只。同日上午继续ig腺嘌呤0.2 g/(kg·d),下午ig相应药物,1周后停止给予腺嘌呤,连续给药22 d,另取10只正常大鼠作为正常对照组。对各组小鼠进行一般检查,末次给药后检测大鼠肾脏系数,血清中钙、磷、甲状旁腺素(PTH)、肌酐、尿素氮含量,以及肾脏病理学变化。结果:与正常对照组比较,模型组大鼠呈现慢性肾衰体征,肾脏系数和磷、PTH、肌酐、尿素氮含量均增加,钙含量减少(P<0.01),肾脏切片呈明显病理学特征。与模型组比较,碳酸镧组、碳酸钙组和氢氧化镧各剂量组大鼠慢性肾衰体征均改善,肾脏系数(除氢氧化镧高剂量组外)和磷(除碳酸钙组外)、PTH(除氢氧化镧低剂量组、碳酸钙组外)、肌酐(除氢氧化镧低剂量组、碳酸钙组外)、尿素氮含量均减少,钙含量和钙磷乘积(仅碳酸钙组)均增加(P<0.05或P<0.01),其余差异无统计学意义;肾脏切片病理学特征好转。结论:氢氧化镧可改善慢性肾衰高磷血症模型大鼠肾功能,降低血清磷含量。     

低剂量砷染毒SD大鼠肝脏差异蛋白的研究

目的观察低剂量急性砷染毒SD大鼠肝脏差异蛋白,为筛选有意义的低剂量砷中毒早期肝脏改变的特异性生物标志物提供依据。方法健康雄性SD大鼠48只,体质量180～220g,按体质量随机分为4组,每组12只,分别饮用含亚砷酸钠0、0.05、0.15、0.45mg/L的水。染毒4周后断头处死。采用双向凝胶电泳技术,对低剂量砷染毒后的大鼠肝脏蛋白表达谱进行分析。结果与对照组相比,0.05mg/L剂量组不表达的蛋白质点数有31个,表达下调的蛋白质点数有11个,表达上调的蛋白质点数1个;0.15mg/L剂量组不表达的蛋白质点数有23个,表达下调的蛋白质点数有15个,没有出现表达上调的蛋白质点数;0.45mg/L剂量组没有出现不表达的蛋白质点数,表达下调的蛋白质点数有8个,表达上调的蛋白质点数1个。结论染砷组肝脏差异蛋白主要表现为表达下调或不表达,染毒0.05mg/L剂量和0.15mg/L剂量不表达和表达下调的蛋白质点较多,其中重复不表达和重复表达下调的蛋白质点居多数,这些重复的蛋白质点可能和低剂量砷中毒肝脏早期损伤有密切的联系。     

杀螟丹对大鼠的亚慢性经口毒性研究

杀螟丹（cartap）属沙蚕毒素类农药，它是1965年由日本成功开发的第1个沙蚕毒素类杀虫剂，也是人类历史上第1次成功利用动物毒素进行仿生合成的动物源性杀虫剂。国内引进使用多年，广泛应用于水稻、蔬菜、茶树及旱粮作物害虫的防治，是一种高效低毒的广谱性农药。在我国农药的使用量大，据农业部统计我国农药年用量为80～100万吨，其中使用在农作物、果树及花卉等方面的化学农药约占95％以上，目前有关杀螟丹的毒性研究甚少。为此本试验进行杀螟丹亚慢性经口毒性研究，以期为评价杀螟丹的毒性及防治其可能不良影响提供依据。     

苍耳子水萃取物对大鼠肝脏毒性作用的实验研究

目的：观察不同浓度苍耳子水萃取物对大鼠肝脏功能与形态的影响,为临床安全使用苍耳子提供实验依据。方法：取苍耳子碎粉22 kg,用65%乙醇提取,用石油醚、乙酸乙酯、正丁醇萃取,回收有机溶剂后得到水萃取物743.6 g。水提取物用含3%吐温80生理盐水配制成28.00 mg/mL和1.12 mg/mL混悬液。144只SPF级雄性SD大鼠,体重（200±10）g,用随机数字表法分为苍耳子水萃取物高剂量组、低剂量组和对照组,每组48只。高、低剂量组分别给予28.00 mg/mL和1.12 mg/mL苍耳子水萃取物混悬液2.5 mL每日2次灌胃,对照组以3%吐温80生理盐水2.5 mL灌胃;均连续28 d。分别于给药开始后7、142、12、8 d和停药后71、4 d观察大鼠被毛、摄食量和活动情况,测量大鼠体重,检测血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、碱性磷酸酶（AKP）水平,取肝脏计算肝脏指数（肝重/体重×100%）,进行肝脏病理分级和评分。结果：苍耳子水萃取物高剂量组大鼠给药28 d内先后出现竖毛、脱毛、疲倦少动、摄食量减少、对外界刺激反应缓慢等症状;低剂量组仅少数大鼠出现少动喜卧、精神萎靡等症状。停药14 d后高剂量组大鼠活动量和摄食量均增加,少动喜卧症状减轻,被毛光泽度恢复。给药212、8 d和停药7 d时,高剂量组大鼠体重（[10.5±4.2）（、10.2±3.1）（、12.1±4.5）g]明显低于低剂量组（[15.3±2.1）（、16.7±4.2）（、17.6±3.2）g]和对照组（[18.6±3.4）（、20.5±5.2）（、19.6±2.5）g],血清ALT（[42.8±3.2）（、49.3±5.9）（、43.2±3.2）U/L]和AST（[108.8±11.7）（、119.8±16.3）（、110.5±17.6）U/L]水平均明显高于低剂量组（[33.7±4.60）（、34.8±5.4）（、33.5±4.9）U/L（,94.7±12.6）（、95.4±10.7）（、96.8±12.8）U/L]和对照组（[31.2±4.3）（、32.5±6.3）、（31.7±5.7）U/L（,92.3±16.2）（、92.9±20.3）（、93.7±16.3）U/L;]血清AKP（[197.2±25.7）（、210.4±41.8）（、189.3±17.6）U/L]水平明显高于低剂量组（[174.3±22.6）（、175.3±27.4）（、176.3±22.8）U/L]和对照组[（171.3±25.6）、（172.5±28.7）（、172.8±26.3）U/L;]给药21、28 d和停药7 d时高剂量组肝脏指数（4.2±0.45、.0±0.7、4.9±0.3）明显高于低剂量组（3.4±0.63、.6±0.53、.9±0.6）和对照组（3.0±0.4、3.2±0.3、3.4±0.5）;给药14、21、28d和停药7d时高剂量组大鼠肝脏病理评分中位数分别为（1.0、1.5、3.0、1.5）,明显高于低剂量组（0.2、0.5、0.9、0.5）和对照组（0.1、0.1、0.2、0.1）。以上各指标高剂量组与低剂量组、对照组间差异均有统计学意义（P〈0.05,P〈0.01）;而低剂量组与对照组间差异均无统计学意义（均P〉0.05）。结论：苍耳子水萃取物致大鼠肝损害与其浓度和作用时间有关;大剂量和长时间用药可加重肝损害。     

丙烯腈染毒双大鼠肝脏钙稳态某此指标的影响

本研究观察了丙烯腈对大鼠肝脏Ｃａ＾２＋－ＡＴＰａｓｅ、Ｍｇ＾２＋－ＡＴＰａｓｅ、ＮＡ＾＋／Ｋ＾＋－ＡＴＰａｓｅ和磷酸化酶ａ（Ｐ－ａ）活性的影响,探讨其对大鼠肝脏钙稳态的影响。结果表明,随着染毒剂量的增大和染毒时间的延长,各ＡＴＰａｓｅ活性均逐渐降低,而Ｐ－ａ的活性却逐渐升高（Ｐ〈０．０１）。其中高剂量（５０ｍｇ／ｋｇ）组的各观察时段和染毒４２天时各染毒组酶活性的变化均具有显著性意义（Ｐ〈０．０５）     

混合蔬菜汁对四氯化碳染毒大鼠脂质过氧化和转氨酶活性的影响

目的　以四氯化碳 (CCl4 )染毒大鼠为肝损伤动物模型 ,观察了胡萝卜、西红柿、甘蓝、莴苣、芹菜、洋葱、茄子、菠菜等 8种蔬菜的混合菜汁对大鼠脂质过氧化和转氨酶活性的影响 ,并探讨其可能机制。方法　将 110只大鼠随机分为 5组 :对照组、CCl4 组、CCl4 +提前给予混合蔬菜汁组、CCl4 + 10 0 %混合蔬菜汁组、CCl4 + 5 0 %混合蔬菜汁组。CCl4 按0 3 5ml kg 1次性腹腔注射 ,混合蔬菜汁按 1ml 10 0g体重灌胃。分别于染毒后第 1天、第 2天、第 7天将各组大鼠随机处死 6只 ,测定血清丙氨酸转氨酶 (ALT)、天冬氨酸转氨酶 (AST)活性 ,血清脂质过氧化 (LPO)水平 ,血清铜蓝蛋白 (CP)含量 ,血清、肝匀浆超氧化物歧化酶 (SOD)活性 ,血清、肝匀浆过氧化氢酶 (CAT)活性。结果　各染毒组肝 体比值增加 ,血清ALT、AST活性增高 ,LPO水平升高 ,各混合蔬菜汁组血清AST、ALT活性均低于CCl4 组 ,以 5 0 %组血清AST、ALT活性最低。结论　在染毒同时给予 5 0 %混合蔬菜汁 ,对CCl4 引起LPO有明显的拮抗作用 ,可能与其能清除·CCl3有关。     

Changes in auditory brainstem response in rats chronically exposed to carbon disulfide

The chronic effect of carbon disulfide (CS₂) on the central nervous system (CNS) was studied by examining auditory brainstem responses (ABRs) in female rats (Jcl Wistar) exposed to 200 ppm or 800 ppm CS₂ by inhalation, 6 h a day, 5 days a week, for 15 weeks. Two modes of ABRs evoked by clicks at 61 and 96 dB sound pressure levels (61 dB-ABR and 96 dB-ABR) were recorded during the exposure and for 6 weeks afterwards. Three main components (I, III and V) of ABRs were analyzed from the latencies and differences between latencies of them (interpeak latencies, IPL I–III, IPL III–V and IPL I–V). The latencies of the three components and IPLs of 96 dB-ABR in rats group exposed to 800 ppm of CS₂ were significantly delayed during the exposure period. The delay of latency of component V and IPL III–V and I–V tended to increase with exposure time. At 61 dB-ABR, the changes in the latency of component V, IPL III–V and I–V resembled those at 96 dB-ABR. For the rats group exposed to 200 ppm CS₂, the latency of component I, IPL III–V and I–V at 96 dB-ABR were delayed significantly but transiently during the exposure period. For both groups, recovery from the latencies of the three components and IPLs of ABR was observed by the end of the recovery period. The delayed latencies of ABR observed in rats exposed to 800 ppm CS₂ suggested a conduction dysfunction in the brainstem due to CS₂ exposure. The transient delay of the parameters in the rats group exposed to 200 ppm CS₂ was considered to represent a slight conduction dysfunction.     

Subacute effects of low dose lead nitrate and mercury chloride exposure on kidney of rats

Lead nitrate and mercury chloride are the most common heavy metal pollutants. In the present study, the effects of lead and mercury induced nephrotoxicity were studied in Wistar rats. Lead nitrate (LN, 45 mg/kg b.w/day) and mercury chloride (MC, 0.02 mg/kg b.w/day) and their combination were administered orally for 28 days. Four groups of rats were used in the study: control, LN, MC and LN plus MC groups. Serum biochemical parameters, lipid peroxidation, antioxidant enzymes and histopathological changes in kidney tissues were investigated in all treatment groups. LN and MC caused severe histopathological changes. It was shown that LN, MC and also co-treatment with LN and MC exposure induced significant increase in serum urea, uric acid and creatinine levels. There were also statistically significant changes in antioxidant enzyme activities (SOD, CAT, GPx and GST) and lipid peroxidation (MDA) in all groups except control group. In this study, we showed that MC caused more harmful effects than LN in rats.     

大鼠原位肝移植手术技巧探讨

目的熟悉大鼠原位肝移植模型的手术步骤,总结手术技巧。方法在传统"二袖套法"基础上,改进部分手术操作,共施行大鼠原位肝移植50例。结果初步建立了大鼠肝移植模型,手术成功率为90%。结论改进方法简便易行,初学者可较快掌握手术操作。     

小剂量氯沙坦治疗大鼠肝硬化门静脉高压症的实验研究

目的探讨小剂量氯沙坦抗肝纤维化和降低肝静脉压力梯度(HVPG)的作用。方法采用复合因素法制作大鼠肝硬化门静脉高压症(PHT)模型,雄性Wistar大鼠随机分为3组:正常对照组7只、模型对照组6只和治疗组10只。治疗组给予氯沙坦2.5mg·kg-1.d-1。结果15d治疗结束后,与模型对照组比较,氯沙坦能够显著降低HVPG[(12.5±1.4)mmHg对(10.1±1.1)mmHg],其中肝静脉楔入压下降为著,且对平均动脉压无明显影响。氯沙坦可以减轻肝纤维化程度,降低血清透明质酸和丙氨酸转氨酶水平。结论小剂量氯沙坦能够安全有效地降低HVPG,减轻肝纤维化而用于肝硬化PHT的治疗。     

改进小体积肝移植供肝大鼠模型建立方法的实验研究

目的探讨改进切肝技术,以建立更可靠的小体积肝移植供肝大鼠模型。方法以Kamada的“二袖套法”为基础,建立30％小体积肝移植中叶供肝大鼠模型。实验分两组：Ⅰ组（28只）,常规方法切肝,以中叶作供肝;Ⅱ组（36只）,改进为左叶和右叶的切肝方法,余方法步骤同Ⅰ组。观察两组手术并发症和7d生存率。结果Ⅱ组肝后下腔静脉狭窄的发生率明显低于Ⅰ组（P〈0．05）,其他并发症发生率两组间无明显差异（P〉0．05）。术后7d生存率Ⅱ组（60％,21／36）高于Ⅰ组（33％,9／28）,但差异未显示有统计学意义（Χ^2=0．272,P〉0．05）。结论采用中叶供肝、改进切肝技术,可以建立更稳定可靠的部分体积肝移植供肝大鼠模型。     

Effect of various non-hepatotoxic compounds on urinary and liver taurine levels in rats

Administration of compounds which alter protein synthesis or sulphur amino acid metabolism in rats results in changes in the excretion of urinary taurine. Treatment with diethylmaleate (DEM) or phorone, which will deplete glutathione (GSH), reduces taurine excretion, whereas treatment with buthionine sulphoximine (BSO), which will inhibit glutathione synthesis, increases taurine excretion. Treatment with cycloheximide, an inhibitor of protein synthesis, increases taurine excretion, whereas pretreatment with phenobarbital, which will increase protein synthesis, decreases taurine excretion. Administration of agents which damage organs other than the liver such as the kidney, heart and testes, does not increase urinary taurine.     

谷氨酰胺对肝硬化大鼠肠屏障功能的保护作用

目的观察谷氨酰胺对肝硬化大鼠肠屏障功能是否具有保护作用。方法采用CCL4+酒精制备大鼠肝硬化模型。30只Wistar大鼠随机分为正常对照组,肝硬化模型对照组及谷氨酰胺治疗组。使用苏木素-伊红(HE)、胶原纤维(VG)染色以及电镜技术从形态学上检测谷氨酰胺对肝硬化程度以及肠功能屏障障碍的改善状况,采用血浆二胺氧化酶和血浆内毒素水平检测各干预组的疗效。结果 VG染色显示谷氨酰胺治疗组肝纤维化程度减轻;HE、电镜结果显示谷氨酰胺治疗组肠屏障结构损伤减轻;门静脉内毒素水平及血浆二胺氧化酶(DAO)水平在肝硬化模型组均显著高于正常对照组(P<0.05),谷氨酰胺治疗组两指标水平均低于同期肝硬化模型组(P<0.05)。结论谷氨酰胺对肝硬化大鼠肠屏障功能具有保护作用。     

The influence of low LSD dose administration during sleep in rats

LSD (subcutaneous infusion of 125 /kg of body weight in 1 ml during 60 min) administered during sleep in rats with implanted electrodes increases the frequency of hippocampal theta activity during paradoxical sleep. Neither the duration of slow wave and paradoxical sleep phases nor the total amount of slow wave and paradoxical sleep was influenced by the drug.     

Changes in the structure and function of the kidney of rats chronically exposed to cadmium. II. Histoenzymatic studies

Early effects of cadmium (Cd) on the structure and function of the kidney were studied in an experimental model using rats intoxicated with Cd at the levels of 5 and 50 mg Cd/l drinking water. The effect of Cd was evaluated histopathologically and biochemically. Damage to the cellular structures was assessed on the basis of histoenzymatic analyses of the activity and localization of indicator enzymes (succinate dehydrogenase, lactate dehydrogenase, glucose-6-phosphatase, Mg²⁺-dependent adenosine triphosphatase and acid phosphatase). The histochemical observations indicate that Cd causes damage to the organization and function of the nephron. Several structures, i.e. endoplasmic reticulum, mitochondrion, lysosome, cellular and intracellular membrane, as well as their biological functions, i.e. aerobic and anaerobic respiration, transport functions and biochemical processes taking place in the endoplasmic reticulum, were affected. The cytotoxic action of Cd occurs mainly in the tubules and partially also in the glomeruli. The results clearly indicate that Cd damages kidney structurally and functionally even at a relatively low level (5 mg/l) corresponding to human environmental exposure, and they confirm our previous hypothesis that the threshold for the kidney effects of Cd is less than 4.08±0.33 g/g kidney wet weight and higher than 2.40±0.15 g/g. The target for Cd action in the kidney is the tubules (proximal convoluted tubules and straight tubules), and disturbance in their function is the main toxic effect of Cd. Renal glomeruli are also injured, but only partially, whereas in other parts of the nephron the damage is slight. The results, together with observations reported in the first paper of the study, incline us to conclude that humans environmentally exposed to Cd are at risk of tubular damage.Electronic Supplementary Material Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00204-003-0500-9     

大鼠酒精肝的实验室检查B超特征与病理对照

目的制备大鼠酒精肝模型,探讨大鼠酒精肝时的超声、病理特征与实验室检查的关系。方法将64只SD大鼠随机分为两组,喂养不同的饮食,观察其在不同阶段的超声表现、血糖、血脂、肝肾功能,与病理结果对照。结果大鼠酒精肝的形成时间最短为42d,最长为84d;典型的酒精肝超声表现为以肝静脉为界,呈不规则的片状高回声,后方无回声增强;丙氨酸转氨酶(ALT)和尿素氮(BUN)增高,天冬氨酸转氨酶(AST)、白蛋白/球蛋白(A/G)、碱性磷酸酶(ALP)降低。结论30%的高粱白酒容易制备大鼠酒精肝模型,超声判断大鼠酒精肝与病理结果相一致,但估测严重性低于病理检查,ALT、BUN、AST、A/G和ALP在大鼠酒精肝时有改变。