生脉饮的大鼠长期毒性研究

目的：研究生脉饮的长期毒性，方法：将大鼠97只分为4组，给药剂量分别相当于成人临床用量的100倍、25倍、5倍和0倍，连续给药90天，每周记录体重1次，并检测血液学，血液生化学指标、脏器系数和组织形态学观察。结果：未见明显毒性反应。结论：生脉饮是安全的。     

牛初乳粉大鼠长期毒性研究

目的 了解牛初乳对大鼠长期毒性。方法 每天按0．83、1．67和3．33g/Bw的牛初乳粉喂饲大鼠30d。实验结束时采血作血生化及血常规检测，统计脏体比并作肝、肾、脾、胃、睾丸、卵巢病理学检查。结果 牛初乳粉对大鼠生长发育无不良影响，血液学、血清生化指标值在正常值范围内，病理学检查未见特异性病变。结论 牛初乳粉对大鼠未表现出明显的长期毒性。     

甘乐胶囊大鼠长期毒性研究

目的 观察甘乐胶囊对大鼠所产生的毒性反应,为临床用药提供安全剂量.方法 甘乐胶囊20.4、40.8、81.6 g/ks(相当于临床剂量的15、30、60倍),连续给药6个月,观察对大鼠体重、心电图、血液细胞学、肝肾功能、系统尸解和脏器系数、组织形态学的影响.结果 灌胃给药6个月小、中、大剂量组与对照组体重增长率分别为433.6%、407.8%、398.7%和414.4%,各剂量组体重与对照组比较差异均无统计学意义(P均＞0.05);仅见大剂量组(临床剂量60倍)肝功能指标ALT、AST明显降低(P＜0.05、P＜0.05)、TP明显升高(P＜0.05);大剂量组动物肝、肾脏器系数增大(P＜0.05、P＜0.05).给药6个月其他检查:心电图、血液细胞学、肾功能、系统尸解和主要脏器病理组织学检查各剂量组与对照组比较差异均无统计学意义(P均＞0.05).结论 甘乐胶囊40.8 g/kg(相当于临床剂量30倍)以下剂量180 d灌胃大鼠无明显毒性反应,提示临床应用比较安全.但需注意在给药剂量较大时(临床剂量60倍)重点观察肝、肾方面的指标.     

珍珠口腔宝大鼠长期毒性试验

珍珠口腔宝临床为0 1g/次,3～5次/d (以0 5g/ 5 0kg人计算,即临床剂量为0 0 1g/kg) ,用药时间为3～7d。长毒试验剂量设计为临床剂量的4 0、80、12 0倍即0 4 g/kg、0 8g/kg、1 2 g/kg ,给药时间为30d ,观察连续重复给受试物对大鼠所产生的毒性反应,为临床用药提供依据。1　实验材料1 1　实验药物　珍珠口腔宝为浅黄色固体粉末,每克相当于原药粉1g ,由某制药公司提供,批号:94 0 6 11。临用时用蒸馏水配成所需浓度。1 2　实验动物Wistar大鼠(封闭群4 0代以上)一级动物,生产合格证号:川实动管第6 0号。体重10 0 g±10 g ,雌雄各半。由四川…     

人参石斛冲剂对大鼠的长期毒性实验研究

目的观察连续灌胃给予大鼠人参石斛冲剂所产生的毒性反应,以确定受试物作用靶器官和无毒反应剂量。方法将SD大鼠雌雄各半,按体重随机分为对照组及高、中、低3个剂量组。给药剂量分别为1 000、500、250 mg·kg1连续灌胃给予26周,给药期间进行一般状态观察,给药结束检测血液学、血液生化学、脏器重量等,并进行病理组织学检查。结果中、高剂量组雌鼠子宫卵巢脏器重量及系数高于对照组,病理组织学检查子宫呈分泌期变化的动物数与对照组比较有所增高,其余未见与用药相关的变化。结论人参石斛冲剂长期连续灌胃给予大鼠未见明显毒性反应,长期服用安全。     

圣母乳宝口服液对大鼠长期毒性的研究

目的 探讨圣母乳宝口服液对大鼠的长期毒性。方法 取大鼠６０只，雌雄各半，随机均分为３组，高剂量组给药２００ｍｌ／ｋｇ／ｄ、低 剂量组给药２０ｍｌ／ｋｇ／ｄ和空白组给水２０ｍｌ／ｋｇ／ｄ，均连续给药２１天。作血液学、血液生化学检查，主要脏器作肉眼及组织学检查。将结果与空白组比较，作统计学处理。结果 高剂量组引起大鼠的血清ＴＰ、ＧＬＵ降低，未上起其它明显毒性反应，停药两周后ＴＰ、ＧＬＵ与空白组比较无显     

香薏冲剂大鼠长期毒性实验

小鼠经口急性毒性实验已测得香薏冲剂的LD50和LDo,该冲剂属基本无毒[1].在此基础上进行大鼠长期毒性实验[2,3,4].观察大鼠对该冲剂的一般表现、体重增长、血象、肝功、肾功、脏器系数,病理组织学等有无变化损伤,为药效及临床应用提供长期毒性实验依据.现将结果报告如下.     

凯龙疫苗先驱论坛——疫苗中的硫柳汞

硫柳汞是一种含汞的有机化合物。自1930年以来．它一直被广泛用作生物产品及药物制剂包括许多疫苗的防腐剂．以预防有害微生物污染所致的潜在危害。疫苗中添加防腐剂是为了防止疫苗发生意外污染时微生物的生长．尤其是在多剂量瓶装制剂的反复取用过程中。事实上．在全世界范围内．多剂量瓶装疫苗中均常规添加防腐剂。另外，在疫     

三聚氰胺对SD雌鼠卵巢毒性的研究

目的:初步探讨不同剂量三聚氰胺对SD雌鼠卵巢的毒性作用。方法:将60只SD雌性大鼠随机分A、B、C、D四组,A、B、C为实验组,D为对照组。分别予以400 mg/kg、800 mg/kg、1 600 mg/kg的三聚氰胺灌胃,1次/日,持续35天,用药结束后24 h处死大鼠。切取卵巢称量湿重、做病理切片、记数各级卵泡。取大鼠卵巢组织固定切片,做HE染色;用免疫组化方法检测P450arom在大鼠卵巢中的分布及表达。结果:A、B、C 3组大鼠卵巢湿重与D组相比明显减轻(P<0.05);B、C组卵巢湿重相比无统计学差异,但与A组相比亦有减轻(P<0.05);A、B、C 3组的总卵泡数、成熟卵泡数、初级卵泡数和生长卵泡数明显少于D组(P<0.05)。与对照组比较,各实验组P450表达强度减弱(P<0.05);B组和C组各级卵泡数均减少,B组伴间质及颗粒细胞的崩解坏死;A组生长卵泡、成熟卵泡数均明显减少。结论:三聚氰胺所致的卵巢毒性与摄入量有一定的相关性。过量的三聚氰胺能够抑制鼠体内细胞色素芳香化酶P450的表达,使体内E2生成障碍,从而影响卵泡发育。     

长期铝摄入对大鼠记忆的影响

目的 通过观察长期摄入不同量的铝对大鼠记忆的影响,进一步探讨铝的神经毒性.方法 选择Wistar成年大鼠40只,随机分4组,分别饮用含Al2（SO4）30.05%,0.5%及2.5%的饮水,即Al^3＋浓度分别为40、400、2000mg/L（低、中、高铝）的饮水并设对照组,各组共饲养6个月后进行被动回避实验.亲代孕前1个月分组,分别饮用低铝和高铝饮水.生下子鼠后摄入高铝饮水分为2组,一组母、子鼠继续饮用高铝饮水,另一组则改为饮用自来水;低铝饮水组母、子鼠继续饮含相应Al^3＋浓度的饮水,各组子鼠达3月龄后进行被动回避实验并与同龄大鼠比较.结果 各组成年大鼠记忆获得均无影响,但高、中铝饮水组大鼠记忆消失明显早于对照组（P＜0.01）,低铝饮水组大鼠记忆消失与对照组无统计学意义（P＞0.05）.生后高铝持续摄入对子鼠的记忆获得及记忆储存均有明显损害（P＜0.01）,但生后即停用铝仅影响记忆储存,低铝摄入对子鼠记忆储存也具明显损害（P＜0.01）.结论 成年大鼠摄铝量高出正常摄入量50倍以上则影响记忆储存,但高出250倍对记忆获得仍无损害.自孕前亲代大鼠即摄铝则对子鼠的毒性最大,低浓度（40 mg/L）即明显子鼠影响记忆储存,高浓度（2 000 mg/L）不仅影响子鼠记忆的储存且影响记忆的获得,且其毒性至少持续到成年.     

黄芩苷对雄性大鼠肝肾毒性作用研究

目的:观察不同剂量黄芩苷给药不同时间对大鼠肝肾的毒性作用,为临床用药的安全性提供实验参考依据。方法:于2019年4月,将42只Wistar雄性大鼠随机分为对照组（0.9%氯化钠溶液,14只）和黄芩苷给药组（100、200 mg/kg,各14只）,经口灌胃,1次/d,6次/周,于给药28、56 d后各组分别处死7只大鼠,...     

氟铃脲原药大鼠亚慢性毒性实验研究

目的了解氟铃脲原药对大鼠的亚慢性毒性,求出最大无作用剂量。方法将80只sD大鼠随机分为4组,每组20只,分别给氟铃脲原药800、400、200、0mg／（kg·d）灌胃染毒90d,每周称量大鼠体重,90天后检测各项血生化指标,测定脏器重量并计算脏器系数,光学显微镜下对脏器进行病理学检查。结果氟铃脲原药大剂量组[800mg／（kg·d）]、中剂量组[400mg／（kg·d）]肝组织病理学检查可见形态改变,血清天冬氨酸转氨酶（AST）活力升高。小剂量组[200mg／（k·d）]各项指标与对照组比较未见异常。结论氟铃脲原药对大鼠有肝脏毒性,最大无作用剂量为200mg／（kg·d）。     

二硫化碳对大鼠雌性性腺毒性研究

本文通过亚慢性二硫化碳腹腔注射染毒,观察二硫化碳对雌性大鼠卵巢锌、铜含量、动情周期以及卵泡细胞生长发育的影响。显示二硫化碳染毒高剂量组大鼠卵巢锌、铜含量均显著低于对照组;染毒组大鼠动情周期均比对照组显著延长;高剂量染毒组大鼠初、次组卵泡数显著低于低剂量组和对照组。表明二硫化碳对雌性大鼠性腺毒性也可表现为动情周期的明显延长,卵巢细胞生长发育过程的明显障碍,而卵巢锌、铜含量降低在其发生机理中的作用值得     

全氟异丁烯 Wistar大鼠动态吸入急性毒性观察

目的 观察Wistar大鼠吸入全氟异丁烯(PFIB)的急性毒性.方法 大鼠分9组分别吸入不同质量浓度(114.2、128.3、149.3、155.8、165.7、177.9、189.6、200.5、219.6 mg/m<'3>)的PFIB 5 min,记录染毒前及染毒后第1、2、7、14天动物体质量,染毒后动物的死亡数,平均每只动物每天摄食量和饮水量.采用Bliss氏法计算半数致死浓时积(LCT<,50>)并比较性别差异;染毒后第14天处死存活动物,进行大体病理观察,取114.2、149.3、200.5、219.6 mg/m<'3>组存活动物肺组织测定肺系数.结果 雌、雄性大鼠LCT<,50>分别为921.3 mg;m<'-3>.min<'-1>、943.5 mg.m<'-3>.min<'-1>;95%置信区间(CI)分别为828.9～1 124.0 mg·m<'-3>·min<'-1>、844.0<'-1> 211.0 mg·m<'-3>·min<'-1>,两者差异无统计学意义.两者合并计算的LCT<,50>为932.1 mg·m<'-3>.min<'-1>,95%CI为863.9～1 049.0 mg·m<'-3>·min<'-1>.在染毒后第14天大体病理检查发现,除219.6 mg/m<'3>组的2只雄性大鼠有较严重的肺水肿,其他各组动物的肺水肿有较好的恢复.但肺部的瘀血、出血点,肠出血、肿胀、灰白色斑块等病理症状随PFIB染毒水平的增加逐渐加重.大鼠吸入PFIB后2d内体质量缓慢下降,而后雌性动物的体质量缓慢上升,而雄性动物的体质量与雌性动物相比上升较快.平均摄食量和饮水量与动物体质量的变化趋势一致.结论 PFIB急性毒性较强,肺是其主要损伤器官,但后期仍伴随其他组织器官的损伤.     

Sensitization to social anxiolytic effects of ethanol in adolescent and adult Sprague-Dawley rats after repeated ethanol exposure

Ontogenetic studies using a social interaction paradigm have shown that adolescent rats are less sensitive to anxiolytic properties of acute ethanol than their adult counterparts. It is not known, however, whether adaptations to these anxiolytic effects on repeated experiences with ethanol would be similar in adolescents and adults. The present study investigated sensitivity to the anxiolytic effects of ethanol in adolescent and adult male and female Sprague-Dawley rats after 7 days of exposure (postnatal day [P] 27-33 for adolescents and P62-68 for adults) to 1 g/kg ethanol or saline (intraperitoneally]) and in animals left nonmanipulated during this time. Anxiolytic effects of ethanol (0, 0.75, 1.0, 1.25, and 1.5 g/kg for adolescents and 0, 0.25, 0.5, 0.75, 1.0, and 1.25 g/kg for adults in experiments 1 and 2, respectively) were examined 48 h after the last exposure using a modified social interaction test under unfamiliar test circumstances. At both ages, repeated ethanol exposure resulted in the development of apparent sensitization to anxiolytic effects of ethanol, indexed by enhancement of social investigation and transformation of social avoidance into social indifference or preference and expression of tolerance to the socially inhibiting effects induced by higher ethanol doses. Evidence for the emergence of sensitization in adults and tolerance at both ages was seen not only after chronic ethanol but also after chronic saline exposure, suggesting that chronic manipulation per se may be sufficient to alter the sensitivity of both adolescents and adults to socially relevant effects of ethanol.     

动式吸入纳米二氧化硅的大鼠肺毒性研究

目的 探讨连续动式吸入条件下不同浓度的纳米二氧化硅(SiO2)是否可以导致大鼠肺部明显的毒性作用.方法 48只雄性SD大鼠按体重随机分成4组,包括分散剂对照组(对照组,生理盐水)和纳米SiO2低剂量组(质量浓度为0.3％)、中剂量组(质量浓度为1.0％)和高剂量组(质量浓度为3.0％).于动式染毒28 d后(每天染毒2h)处死动物,采集肺泡灌洗液(BALF)和肺组织,观察肺脏器系数、BALF中白细胞总数及分类、总蛋白含量、乳酸脱氢酶(LDH)活力、肺组织病理改变(HE染色)和肺纤维化形成情况(VG染色).结果 与对照组相比,纳米SiO2组肺脏器系数的差异无统计学意义(P＞0.05).1.0％和3.0％纳米SiO2组BALF中的白细胞总数明显高于对照组,差异有统计学意义(P＜0.05).各剂量纳米SiO2组的总蛋白含量和LDH活力与对照组比较,差异均无统计学意义(P＞0.05).与对照组相比,各剂量纳米SiO2组淋巴细胞的比例明显降低,单核和巨噬细胞的比例明显升高,差异有统计学意义(P＜0.05).HE染色显示,纳米SiO2组肺泡壁明显增厚,支气管和血管壁周围发生明显的炎性细胞浸润,各纳米SiO2组肺纤维化VG染色均未见胶原纤维分布的明显增加.结论 本实验条件下,连续28d动式吸入纳米SiO2只引起大鼠肺部显著的炎症反应,未出现肺纤维化现象.     

Repeated dose intramuscular injection of the CIMAvax-EGF vaccine in Sprague Dawley rats induces local and systemic toxicity

CIMAvax-EGF consists of a human recombinant epidermal growth factor (EGF), coupled to P64k, a recombinant carrier protein from N. meningitis, and Montanide ISA 51 as adjuvant. The vaccine immunization induces a specific antibody production, inhibiting the EGF/EGF-R interaction through EGF deprivation. The objective of this study was to assess the CIMAvax-EGF toxicity in Sprague Dawley rats after intramuscular administration of repeated doses (6 months) and at the same time to determine if rat is a relevant species for studying CIMAvax-EGF vaccine. Rats were randomly distributed into four groups: control, Montanide ISA 51, treated with 1× and 15× of human total dose of the antigen. Animals were immunized weekly during 9 weeks, plus 9 immunizations every 14 days. Rats were inspected daily for clinical signs. Body weight, food consumption, and rectal temperature were measured during the administration of doses. Blood samples were collected for hematological, serum biochemical determinations and EGF titles at the beginning, three months and at the end of experimentation. Gross necropsy and histological examination of tissues were performed on animals at the end of the assay. Vaccine provoked the apparition of antibodies against EGF in the rats, demonstrating rat species relevance in these studies. Body weight gain, food and water consumption were not affected. CIMAvax-EGF and Montanide ISA 51 produced local damage at the administration site, showing multiple cysts and granulomas. Both vaccine-treated groups showed neutrophil elevation, besides an AST increase probably related to the damage at the administration site. Rectal temperature was found to be significantly higher in 15× treated group after immunizations, probably induced by the inflammatory process at the injection site. In summary, the clinical pathology findings together with the body temperature results, appear to be caused by the inflammatory reaction at the administration site of the vaccine, mainly mediated by the oil-based adjuvant Montanide ISA 51, probably enhanced by the immunological properties of the antigen. This study showed evidences that intramuscular administration during 26 weeks of CIMAvax-EGF at doses up to 15× human total dose is well tolerated in rats and it has a clinical importance since this long lasting study in relevant species allows to treat cancer patients with tumors during long periods with relative weight safety margin.     

Oral toxicity of indium in rats: single and 28-day repeated administration studies

Indium is widely used in the electronics industry to make semiconductors, liquid-crystal panels, and plasma display panels, and its production is increasing. However, it is necessary to handle it more cautiously than before, because the pulmonary toxicity of inhaled indium has been identified. The present study aimed to characterize the potential toxic effects of indium through oral administration and observation for fourteen days following a single dose of 0 or 2,000 mg/kg (acute oral toxicity study), and repeated oral administration for 28 days at dose levels of 0, 40, 200, or 1,000 mg/kg daily (28-day repeated oral dose toxicity study) to male and female Crj:CD (SD) IGS rats (SPF). No deaths and no abnormalities in clinical signs, body weights, and necropsy findings were observed for any of the animals in the acute oral toxicity study. Furthermore, no changes related to indium were also observed in the dose groups up to 1,000 mg/kg of the 28-day repeated oral dose toxicity study. From the results described above, the lethal dose 50% (LD(50)) of indium is greater than 2,000 mg/kg under these study conditions, and the no-observed-adverse-effect-level (NOAEL) is considered to be 1,000 mg/kg for males and females under these conditions.