半夏及其炮制品对SD大鼠的毒性作用

为研究半夏及其炮制品对大鼠心、肝、肾的毒性作用,将SD大鼠随机分为正常组、生半夏组(3 g/(kg·d))、法半夏组(3 g/(kg·d))、清半夏组(3 g/(kg·d))和姜半夏组(3 g/(kg·d)),连续灌胃21 d后,检测各组血清天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、尿素氨(BUN)、肌酐(Cr)、肌酸激酶(CK)和乳氨酸脱氢酶(LDH)的变化。用HE染色观察心肌组织病理变化,蛋白免疫印迹(Western blot)法测定心肌组织中TGF-β1/Smads/mTOR信号通路相关蛋白的表达。结果发现生半夏经炮制加工后的法半夏、姜半夏和清半夏炮制品的毒性较生半夏的毒性减弱,即对心、肝、肾均无毒性影响。可见合理炮制对半夏的心毒性的减毒作用有显著的改善,有助于临床半夏合理用药。

辛硫磷和灭多威对雄性大鼠生殖系统的联合毒性作用

背景与目的:观察辛硫磷(phoxi m,Pho)和灭多威(methomyl,Met)对雄性大鼠生殖系统的联合毒性作用。材料与方法:选择健康成年雄性SD大鼠24只,按2×2析因设计随机分为4组:即Pho(1/50 LD50,25.20 mg/kg)、Met(1/50 LD50,0.47mg/kg)、Pho+Met(25.20 mg/kg Pho+0.47mg/kg Met)和阴性对照组(蒸馏水)。灌胃染毒每天1次,每周5 d,连续染毒60 d。末次染毒24 h后测量大鼠体重增长量、脏器湿重,精子参数(精子计数、活率、畸形率),血清和睾丸中氧化损伤相关判定指标:超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽S转移酶(GST)、谷胱甘肽(GSH),睾丸标志酶:酸性磷酸酶(ACP)、乳酸脱氢酶(LDH)、ATP酶,血清中雄性激素睾酮(T),睾丸及附睾组织形态等的改变。结果:辛硫磷和灭多威混配对精子数量、活率、畸形率、和睾酮存在协同作用,对血清中SOD、GSH和睾丸组织中SOD、GST、GSH、ACP及Na+-K+-ATPase等存在拮抗作用,对其它指标尚未观察到交互作用。辛硫磷和灭多威混配引起的睾丸组织形态学变化主要表现为生精小管管腔内可见脱落的各级生精细胞,部分生精小管生精细胞层数和各级生精细胞数量均减少,细胞排列疏松紊乱,管腔内成熟精子数量减少,附睾未见明显组织病理学变化。结论:辛硫磷和灭多威混配染毒对雄性大鼠生殖系统存在联合毒性作用,对精子数量、活率、畸形率和血清睾酮水平呈协同作用,对部分氧化损伤指标和睾丸标志酶呈拮抗作用。提示辛硫磷和灭多威混配后对雄性大鼠生殖系统的毒作用可能是通过影响睾丸功能、激素水平和精子发生及成熟过程,导致雄性生殖功能的降低。

新生大鼠在1-氨基-3,5-二甲基金刚烷盐酸急性毒理实验中的毒性反应

目的研究1-氨基-3,5-甲基金刚烷盐酸(美金胺)对SD新生大鼠的急性毒性反应.方法在对47只SD新生大鼠进行美金胺死亡剂量预初实验、得出新生大鼠100%死亡剂量和最大耐受剂量的基础上,将60只新生大鼠根据所选剂距随机分为5组,并设对照组,每组10只,分别经腹腔注射不同剂量美金胺和注射用水,观察毒性反应并应用Bliss方法计算美金胺的半数致死量(LD50)值.结果美金胺在SD新生大鼠LD50值为(74.386+2.811)mg/kg,95%可信区间为59.334～93.257mg/kg.大鼠多在用药后1～4 min出现不良反应,较低剂量组(52.0、61.2、72.0 mg/kg)主要表现为兴奋性颤动、共济失调、呼吸减慢和抑制,部分表现为侧卧、皮肤发绀和呼吸衰竭.较高剂量组(85、100 mg/kg)主要表现为明显的抑制症状、呼吸衰竭、侧卧、皮肤发绀,无颤动及共济失调.死亡新生大鼠多在用药后1 h左右死亡,存活新生大鼠于用药后4～5 h毒性反应消失.结论美金胺不同剂量对新生大鼠均产生毒性反应,新生大鼠的毒性反应及死亡率与美金胺的剂量呈正相关,剂量越大,毒性反应越重,死亡率越高,提示美金胺应用于临床时应密切监测其毒性反应.

三聚氰胺对大鼠肾脏毒性损害的病理研究

目的：大鼠喂食含三聚氰胺饲料后观察肾脏损害的病理所见、生化改变及其超声表现。方法：实验动物随机分为2组，每组20例，第1组为正常对照组，给予正常维持鼠料20d；第2组为研究组（亚急性损害组），喂食掺有三聚氰胺的鼠料20d，每组完成饲养后先做超声检查，观察大鼠肾脏的形态、大小、皮质厚度、实质回声情况及肾内是否有结石形成，然后留取尿液、静脉血做相关检验，最后解剖大鼠，留取双侧。肾脏标本，福尔马林浸泡，待病理切片观察。结果：正常对照组病理所见、生化结果、超声表现未见异常改变。研究组超声显示20只大鼠的40个肾脏实质部回声增强，肾内均可见散在多发的细小强回声结石影，较大者位于集合系统内，伴有声影；8个肾脏出现集合系统分离；实验室检查14只大鼠出现结晶尿，其中8只出现三聚氰胺结晶，20只大鼠尿素升高，10只肌酐增高，14只出现二氧化碳结合率降低；研究组有不同程度病理损害，典型表现有肾组织广泛淤血伴灶性出血，’肾小管伴有点状坏死及成纤维细胞增生，数个肾小管（以皮质肾小管为多）内可见黄绿色针状扇形排列结晶体，相应肾小管扩张，部分区域间质内可见数个淋巴细胞浸润。结论：三聚氰胺可引起大鼠肾脏病理损害，并可导致结石形成，沉积于肾脏，造成肾损害。

医疗器械重复接触全身毒性试验新方法的研究--大鼠胃肠外双途径接触试验

为评价医疗器械极性及非极性可沥滤物同时接触人体时产生重复接触全身毒性的可能性,该研究设计了大鼠胃肠外双途径接触试验法并验证其可行性。本研究设计了空白对照组,腹腔注射玉米油组和胃肠外双途径接触组(尾静脉注射生理盐水,同时腹腔注射玉米油)。试验期间每天进行临床观察,每周称重。14 d后,取血进行临床病理检测、大体病理以及组织病理学检查并将数据进行统计学分析。与对照组相比,双途径接触组各项指标均未见毒性相关性改变。结果表明该试验法能够使大鼠同时充分接触极性及非极性浸提介质又不引起不良病理反应。

20种食品防腐剂抗氧化剂的分子结构与其急性毒性的相关关系研究

对苯甲酸等14种食品防腐剂及叔丁基对苯二酚等6种食品抗氧化剂的大鼠急性经口毒性[Log(LD50)]与其化学结构的关系进行了探讨,求出了这些防腐剂、抗氧化剂的部分分子连接性指数,并参照图论法对分子中各种基团进行了分类。采用多元线性拟合法,求出了各防腐剂分子中各种基团的个数及分子连接性指数与其大鼠急性经口毒性关系的回归方程,能得到方程的计算值与文献值一致的结果。

葛黄神箭片长期给药的安全性评价

目的观察葛黄神箭片(葛根总黄酮、黄柏总生物碱和鬼箭羽水提物)长期给药对大鼠的毒性反应。方法 SD大鼠128只,随机分成4组。给药组分别灌服葛黄神箭片4.37、1.94、0.73 g/kg,对照组同法给予等容量蒸馏水,连续给药27周,恢复期4周,每周称体质量和食耗量,在给药和恢复期间,取血检测血液、凝血、血清生化、电解质等指标,主要脏器称定质量,并作组织病理学检查。结果葛黄神箭片灌胃给药,可使大鼠耗食量减少,体质量增长缓慢,总胆固醇降低,还可使雌性大鼠子宫腔扩张,子宫内膜水肿、上皮脱落、核碎裂,乳腺导管扩张等。但上述反应可能与其药性、主要药效学活性以及富含葛根素等异黄酮类成分有关。结论葛黄神箭片经口长期给药的安全剂量为4.37 g/(kg·d),相当于临床推荐剂量的90倍。但对于育龄期妇女,建议就其长期给药的雌激素样作用作进一步观察。

发酵型大豆乳的毒理性试验研究

本文以纯大豆发酵豆乳为样品 ,对其进行了第一、二阶段的食品毒理性的试验研究 ,即大鼠经口急毒性试验 ;小鼠骨髓微核试验 ;小鼠精子畸形试验 ;Ames试验研究。结果表明 :该样品无急性、亚急性毒性。可做为常见食品进入市场 ,产品安全性是有保证的。

Chronic Toxicity of a Novel Recombinant Human Granulocyte Colony-stimulating Factor in Rats

Objective To assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship.Methods A total of 100 Sprague-Dawley rats (equal numbers of male and female) were randomly divided into five groups (20 rats in each group):four groups were treated with rhG-CSFa at 500,100,10,1 μg/kg,respectively,and one group was treated with vehicle only to serve as the control.The rats were received subcutaneous injections of rhG-CSFa or vehicle daily for 13 weeks.During the course of the chronic toxicity study,the physical status,body weight,and food consumption were monitored.Half of the rats in each group (n=10) were sacrificed after the last rhG-CSFa administration,and the other half were sacrificed at five weeks after the last rhG-CSFa administration.Urinalyses,blood biochemistry,hematological analysis,histopathological examination,and immunological tests were performed for each of the rats.Results The hematological analyses revealed that the mean white blood cells count,neutrophils count,and neutrophils percentage were increased in male rats at the dose of 10 μg/kg or higher,and these were related with the biological activity of rhG-CSFa.Some small abnormalities were observed in the spleen of a few rats when used highest dose (500 μg/kg,a dosage of 200 folds higher than the normal clinical dosage),but these abnormalities were recovered within 5-week recovery period.No other rhG-CSFa-related abnormalities were observed in this chronic toxicity study.Conclusion No significant toxicity and immunogenicity are observed with rhG-CSFa administration to rats in the chronic toxicity studies.

Acute Toxicity Test of Qiangli Bupi Paste

[Objective] The toxicity of Qiangli Bupi Paste was investigated, to provide a test basis for its further development and safe use. [Method] Forty Kunming mice, half male and half female, were selected and divided into the CK group and the Qiangli Bupi Paste group, each of which included 20 mice. The acute toxicity of Qiangli Bupi Paste was observed by the maximum administration dosage method. No mice and abnormal response were observed within 14 d in various groups. The tested animals were also subjected to anatomical observation. [Result] All the tested animals survived in the test, and behaved normally, with glossy hair. Their body weights accorded with the growth regularity. During the anatomy, no important vis- ceral organs showed pathological changes, and there were no significant differences in body weight between the two groups before administration, on the 7~ after ad- ministration and the 14 d after administration （P〉0.05）. [Conclusion] In the acute toxicity test of Qiangli Bupi Paste, the maximum administration dosage was 48 g/kg （equivalent to 96 times of the daily dose of adult in clinic）, and no obvious toxic response was observed.

The Protective Role of β-Carotene and Hesperidin on Some Hematological and Myocardial Measurements against Imidacloprid Toxicity in Albino Rats

Neonicotinoids including IM （Imidacloprid） are widely used as plant systemic insecticides. Several studies have indicated that pesticide toxicity may be associated with the enhanced production of ROS （reactive oxygen species）. Both β-carotene （I3C） and hesperidin （H） have an antioxidant property and quench free radicals. This study aimed to clarify the protective role of β-carotene and hesperidin as natural antioxidants on IM induced toxicity in hematological parameters and markers of cardiac muscle activity in male albino rats. The treatment of rats with IM showed a significant decrease in hemoglobin （Hb %）, MCH （mean corpuscular hemoglobin）, MCHC （mean corpuscular hemoglobin concentration）, HCT （hematocrit） values and RBCs count comparing with control group. On the other hand, MCV （mean corpuscular volume）, WBCs （white blood cells） and Pits （platelets） count pronounced a significant increase in IM group comparing to control. Also, αFP （plasma alpha fetoprotein）, CEA （carcinoembryonic antigen）, CK （creatine kinase）, CK-MB （creatine phosphokinase myocardial band） and LDH （lactate dehydrogenase） clarify a significant increase in IM group comparing to control. Both β-carotene and hesperidin mitigate the deleterious effects of IM on previous parameters. β-Carotene and hesperidin may protect hematopoietic system and heart muscle against toxicity of IM. These improvements of the results clarify the protective effect of the used antioxidants. Conclusion： β-carotene and hesperidin, natural antioxidants, have a protective effect against IM evoked hematological and biochemical changes.

纳米银对大鼠亚急性毒性研究

目的研究纳米银对大鼠的亚急性毒性。方法将40只Wistar大鼠随机分为4组，雌雄各半，以生理盐水为对照组以及3种浓度纳米银水溶液灌胃染毒14天后处死大鼠，称取脏器重量，计算脏器系数，测定大鼠血清某些生化指标，血液学指标并对脏器组织进行病理学观察。结果各染毒组心、肝、脾、肺、肾系数与对照组无明显差异；高剂量组碱性磷酸酶（ALP）活性均较对照组升高（P〈0.05）；染毒组动物的肝细胞出现少量线粒体外膜模糊。结论本实验条件下高剂量的纳米溶液可对大鼠肝脏产生一定程度损伤作用。

Single and Repeat Dose Toxicity Study of 7-Hydroxycoumarin, Ethanol, and Their Mixture in Rats

Acute and repeat-dose toxic effects ofHOC （7-hydroxycoumarin）, ethanol and their mixture were studied in rats. Single oral administration of HOC （5,000 mg/kg） caused transitional glycosuria associated with lowered serum glucose levels, decreased urea clearance. HOC given orally during 28 days （200 mg/kg） decreased serum glucose, and increased serum triglyceride concentrations. No enhancement of acute toxic effect of HOC （5,000 mg/kg） and ethanol （6,000 mg/kg） mixture was found in the acute toxicity study phase. Effect of HOC （200 mg/kg） and ethanol （750 mg/kg） during 28 days of exposure was less pronounced in comparison with HOC effect only, as far as neither decrease of glucose, nor increase oftriglyceride serum concentrations were found.

“量-权-证”网络毒理学的提出与应用:以八角莲醇提液致肝毒性为例

该研究首次提出"量-权-证"网络毒理学的研究方法,通过将毒性成分含量及成分作用靶点的频次赋予靶点权重,将传统定性网络转为定量网络,不断提高获取数据的信度,为系统性评价中药安全性及毒理学研究提供研究思路。首先,给予大鼠灌胃八角莲50%醇提物,基于血清药物化学辨识其中成分。随后从SwissTargetPrediction、PharmMapper等数据库获取成分靶点,以成分相对含量和钓靶频次赋予靶点权重,Comparative Toxicogenomics Database(CTD)、GeneCards等数据库预测肝毒性靶点,通过STRING数据库进行蛋白质互作分析及通路富集分析。最后,构建"毒性成分-加权靶点-效应通路"定量网络。八角莲体内外成分分析共筛选得到鬼臼毒素、鬼臼毒酮、去氧鬼臼毒素、6-甲氧基鬼臼毒素等11个潜在毒性物质,涉及肝毒性作用靶点106个,加权靶点涉及Cdk2、Egfr、Cyp2c9等65个。京都基因与基因组百科全书数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析表明其可能通过作用于PI3K-AKT、MAPK、Ras等信号通路呈现炎症反应、氧化应激、细胞凋亡、介导细胞色素P450(CYP450)酶系发挥肝毒性作用,然传统方法显示AKT1、Alb、Stat3等51个靶点可能通过介导炎症作用、细胞增殖等导致肝损伤,可知从不同层面获取的毒性机制有较大差异。综上,该研究提出并系统性应用"量-权-证网络毒理学"于八角莲致大鼠肝毒性机制研究,证实其广泛应用于中药毒理学评价的可行性,进一步完善中药安全性系统评价的思路。

Toxic effects of Litsea elliptica Blume essential oil on red blood cells of Sprague-Dawley rats

Litsea elliptica Blume leaves have been traditionally used as medicinal herbs because of its antimutagenicity,chemopreventative and insecticidal properties. In this study,the toxic effects of L. elliptica essential oil against Sprague-Dawley rat’s red blood cells (RBCs) were evaluated. L. elliptica essential oil was given by oral gavage 5 times per week for 3 treated groups in the doses of 125,250,and 500 mg/(kg body weight),respectively,and the control group received distilled water. Full blood count,RBC osmotic fragility,RBC morphological changes,and RBC membrane lipid were analyzed 28 d after the treatment. Although L. elliptica essential oil administration had significantly different effects on hemoglobin (Hb),mean cell hemoglobin concentration (MCHC),mean cell volume (MCV),and mean cell hemoglobin (MCH) in the experimental groups as compared to the control group (P<0.05),the values were still within the normal range. L. elliptica induced morphological changes of RBC into the form of echinocyte. The percentage of echinocyte increased significantly among the treated groups in a dose-response manner (P<0.001). The concentrations of RBC membrane phospholipids and cholesterol of all treated groups were significantly lower than those of control group (P<0.001). However,the RBC membrane osmotic fragility and total proteins of RBC membrane findings did not differ significantly between control and treated groups (P>0.05). It is concluded that structural changes in the RBC membrane due to L. elliptica essential oil administration did not cause severe membrane damage.

Effect of Xixin decoction on phosphorylation toxicity at specific sites of tau protein in brains of rats with sporadic Alzheimer disease

OBJECTIVE: To explore the mechanism of action of Xixin decoction(XXD) for the prevention and treatment of sporadic Alzheimer disease(SAD) by investigating the effects of XXD on the phosphorylation of Thr231 and Ser422 sites of tau protein. METHODS: Specific pathogen-free(SPF) male Sprague-Dawley(SD) rats with SAD were randomly divided into six groups: sham-operated, model(intracerebroventricular injection of Streptozotocin, ICV-STZ), donepezil(0.92 mg/kg), XXD low-dose(7.61 g/kg-1 ·d-1), moderate-dose(15.21 g/kg-1 ·d-1), and high-dose(30.42 g/kg-1 ·d-1). Immunohistochemistry and western immunoblotting were used to detect the phosphorylation at Thr231 and Ser422 sites of tau protein. RESULTS: XXD different dose groups decreased to varying degrees the expression of phosphorylated tau at P-Thr231 and P-Ser422 sites in the hippocam-pus of SAD rats. No significant difference was found between the donepezil and model group. CONCLUSION: XXD may prevent SAD pathological progress by inhibiting hyperphosphorylation at the key sites of tau proteins.