硒锌对大鼠肾脏氧化应激、细胞凋亡和增殖周期的影响

将亚硒酸钠和硫酸锌配伍制备低剂量 (0 .1mg/ kg体重 Na2 Se O3 和 14.8mg/ kg体重 Zn SO4· 7H2 O)和高剂量 (0 .2 mg/ kg体重 Na2 Se O3 和 2 9.6 mg/ kg体重 Zn SO4· 7H2 O)硒锌制剂 ,通过灌胃方式给予 Wistar大鼠 ,6个月后用 TUNEL 法和流式细胞术检测大鼠肾脏细胞凋亡和细胞增殖周期的变化。结果表明 ,低剂量和高剂量硒锌均能明显诱导大鼠肾脏细胞凋亡 ,低剂量硒锌对细胞增殖周期不产生明显影响 ,而高剂量硒锌使 G2 / M期细胞减少 ,DNA相对含量下降。研究提示 :一定剂量硒锌能有限改善机体抗氧化能力 ,但仍可诱导肾脏细胞凋亡并影响 DNA合成 ,使细胞滞留于 S期 ,改变细胞增殖周期     

苯对小鼠胚胎发育的毒性作用研究

目的探讨苯对小鼠胚胎体内发育的毒性。方法随机选择健康性成熟的昆明种小鼠,雌雄合笼产生孕鼠,孕鼠被随机分成5组（溶剂对照组、高、中、低剂量苯染毒组和环磷酰胺染毒组）,每组8只,分别在小鼠妊娠第6-15天用25（低剂量）、100（中剂量）、400 mg/kg.d（高剂量）的苯进行灌胃染毒,每天一次,同时设植物油溶剂对照和环磷酰胺（10 mg/kg体重）阳性对照。观察孕鼠的体重增长情况;于妊娠第18天处死孕鼠取出胚胎,观察胚胎的生长发育状况、死胎和吸收胎鼠数及畸形发生情况。结果与植物油对照组比较,中、高剂量苯染毒可降低孕鼠体重的增长率（P〈0.05）,高剂量苯染毒孕鼠能使胚胎吸收和死亡发生率增加（P〈0.05）,并可抑制胎盘和胎仔生长发育,中、高剂量苯染毒导致胎鼠畸形发生率增加（P〈0.05）,但对孕鼠和胎仔的毒作用影响均弱于环磷酰胺的毒性作用（P〈0.05）。结论苯在体内对小鼠胚胎具有发育毒作用和致畸形作用。     

葡甲胺对顺铂所致肾损害的预防作用

目的：观察葡甲胺（NMG）对顺铂（CP）染毒大鼠相关指标的影响,初步确定NMG预处理对CP所致大鼠肾损伤的预防作用。方法：以不同剂量NMG预处理后给予CP,收集染毒后60－72h,108-120h尿液,分别于染毒后3d,5d处死动物留取血液及肾脏,测定相关指标。结果：NMG预处理可明显降低CP所致大鼠肾脏系数升高,抑制血尿素氮（BUN）、尿蛋白、丙二醛（MDA）含量升高,并随NMG剂量升高,作用越显著,存在一定的剂量－反应关系。结论：NMG预处理能明显预防CP所致肾损伤。     

他克莫司与环孢霉素治疗单纯性V型狼疮性肾炎的疗效比较

目的比较他克莫司（Tacrolimus,TL）与环孢霉素（Cyclosporine,CsA）联合激素治疗单纯性V型狼疮性肾炎的疗效及安全性。方法选择本院确诊为V型狼疮性肾炎的35例患者,比较同期激素联合TL[0.07-0.08mg/（kg·d）,n=17例]与激素联合CsA[3-5mg／（kg·d）,n=18例]治疗6个月的疗效。主要观察治疗前后SLE-DAI、尿蛋白、血清白蛋白、血清补体C3、anti-dsDNA和ANA阳性率的变化,以及治疗前后的完全缓解率、部分缓解率。结果CsA或TL治疗后,治疗指标均出现明显的改善,其中,6个月治疗效果更为明显。治疗3个月TL组与CsA组有效率分别为77.7％和58.8％,经比较两组差异无统计学意义（P〉0.05）,但是,3个月TL治疗组在降低SLE-DAI、24h蛋白尿和增加血清白蛋白方面疗效比CsA组更明显（P〈0.05）。治疗6个月TL组有效率及治疗指标的改善均较好于CsA组,但差异无统计学意义（P〉0.05）。TL组无严重副作用出现。结论TL联合激素治疗单纯性V型狼疮性肾炎是有效和安全的。与CsA相比,TL可迅速缓解单纯性V型狼疮性肾炎患者蛋白尿和LN狼疮的活动。     

Caffeine Exposure Causes Immune Dysfunction and Intrauterine Growth Restriction Retardation in Rats

<正>This study was conducted to assess the effects of caffeine on the dam and the physical development of rat offspring.Pregnant Sprague-Dawley rats (20per dose group) were administered caffeine by gavage at 0 (control),5,20,and 80 mg/kg body weight bw daily from gestational day 6 through lactation using caffeine dissolved in water.The developmental toxicity of caffeine was evaluated.     

The effect of CYP3A5 polymorphisms on the pharmacokinetics of tacrolimus in adolescent kidney transplant recipients.

BACKGROUND: CYP3A5 gene polymorphism has been shown to influence tacrolimus (TAC) blood concentration and dose requirement in adult kidney transplant patients. The aim was to analyze retrospectively the modification induced by CYP3A5 gene polymorphism on TAC's pharmacokinetic parameters obtained from 26 adolescents receiving TAC as their main immunosuppressive drug. MATERIAL/METHODS: The adolescent kidney transplant patients were genotyped for CYP3A5*3 and grouped accordingly. TAC dose, blood levels, and dose-normalized TAC blood concentration and volume of distribution obtained at different post-transplant periods during the first post-transplant year were correlated with the corresponding genotype. RESULTS: During the first three months post-transplant, heterozygotes (CYP3A5*1/*3) displayed a lower TAC blood concentration than homozygotes (CYP3A5*3/*3) (at 1 month: 7.8+/-2.1 vs. 13.4+/-6 ng/ml, p=0.007) despite a therapeutic monitoring strategy. Between 3-12 months post-transplant, TAC blood concentration was comparable between the two groups, but a two-fold increase in the daily drug dose was necessary for the heterozygotes (at 6 months: 0.23+/-0.1 vs. 0.13+/-0.06 mg/kg, p=0.04). The dose-normalized TAC concentration [(ng/ml)/(mg/kg)] was significantly lower in patients displaying the CYP3A5*1/*3 polymorphism (at 2 weeks: 33+/-2.16 vs. 71.1+/-37.8, p=0.01; 6 months: 35.4+/-12.9 vs. 85.2+/-58.9, p=0.01). At the same time, the volume of distribution of the drug in the latter group was distinctly increased for the entire post-transplant year (at 6 months: 1.79+/-0.42 vs. 0.73+/-0.5 l/kg, p=0.001). CONCLUSIONS: The great influence of CYP3A5 on the pharmacokinetics and pharmacodynamics of TAC in young transplant recipients suggests the need for pre-transplant screening of this polymorphism to improve TAC therapy.     

金石散的慢性毒性试验

金石散慢性毒试验取豚鼠和大鼠进行。１．取５０只豚鼠,随机分为５组,即高、中、低剂量组及ＵＤＣＡ和生理盐水两组为对照组。每只豚鼠每日经口灌服相应药物,１月后采血作肝、肾功能测定。２．取８０只大鼠,随机分为４组,即高、中、低剂量为生理盐水组,每日灌服相应药物,连续９月。其中半数动物在６个月时采血作肝、肾功能试验。９月后处死,作各主要脏器功能及组织学检查,包括体笪、血、尿常规、血生化指标如血糖、血清东西     

Evaluation of the teratogenic potential of pyrazinamide in Wistar rats

We have tested Pyrazinamide (PZA), an essential component of modern short-course tuberculosis treatment regimen, for teratogenicity using Wistar rats. The drug was given by oral intubation from 6-15 days of gestation, at doses of 0, 25, 100 and 500 mg/kg body weight per day. Reduction in body weight and food consumption were observed in the treated dams. On day 20 of gestation, all the dams were killed by cervical dislocation and signs of maternal toxicity, reproductive indices and fetal measurements were recorded. Dams given doses of 100 and 500 mg/kg had significantly higher incidence of reabsorbed fetuses, reduced litter size, and impaired neonatal growth than those given no PZA or only 25 mg/kg dose. External visceral and skeletal examination of all fetuses of PZA-treated dams showed several types of variations which were neither dose related nor having a consistent pattern. However, these variations occurred mostly in the dams treated with the dose of 500 mg/kg. In conclusion, these data show that in Wistar rats, only high doses of PZA (100 and 500 mg/kg) produced fetotoxicity. No evidence of teratogenic effect of the drug was observed.     

三聚氰胺等物质给予幼年恒河猴的毒性试验

目的观察三聚氰胺及其同系物给予动物后,导致肾脏损伤、形成结石的过程,及肾脏损伤的恢复过程。方法选择6月龄恒河猴6只,雌雄各半,随机分为3组,2只/组,分别为T1(140 mg/kg三聚氰胺和14 mg/kg三聚氰酸),T2(140 mg/kg三聚氰胺和50mg/kg腺嘌呤)和T3组(140mg/kg三聚氰胺)。连续70 d口服受试物,观察动物的一般状态,分别于不同时间点进行血液学、血生化、尿常规和肾脏B超的检测;并连续观察18个月,观察动物的生长发育情况。结果 1.各剂量组动物在给予受试物8周后所有动物肾脏中均出现多个结石;停止给予受试物后,所有动物结石数量和大小均呈下降趋势,至停止给予受试物16个月后,全部动物肾脏均未检测出结石。2.各剂量组,血清中β2微球蛋白(β2-MG)和尿酸(UA)等指标随着给药时间的延长而有所增高,但在正常范围内。在动物的恢复期,此两项指标的数值明显下降。结论 1.单纯三聚氰胺(相当于人体使用量48 mg/kg.w.d)不能造成恒河猴肾脏功能的明显损害,可形成肾结石。2.在三聚氰酸或腺嘌呤存在的情况下,三聚氰胺可以造成恒河猴肾功能指标β2-MG和UA在正常范围内升高,并可在肾脏形成结石;。3.经过16个月的恢复所有动物结石无法检出,其中三聚氰胺组动物恢复最快。     

硒对阿霉素所致大鼠心肌损害的保护作用

本文研究了硒对阿霉素所致大鼠心肌损害的保护作用。给大鼠腹腔注射阿霉素3mg/kg隔日1次,共4次,可引起实验动物血和心肌谷胱甘肽过氧化物酶(GSH-Px)活性明显降低,血清磷酸肌酸激酶(CPK)活性明显增高,同时发生心脏的组织病理学改变和心功能不全。从注射阿霉素之前1周开始腹腔注射亚硒酸钠0.2mg/kg,连续14日,以后每周2次,可使受阿霉素影响的GSH-Px和CPK活性得到恢复,并使心脏结构和功能的病理改变减轻。     

吡咯烷二硫氨基甲酸对小鼠大剂量顺铂肾毒性损伤的防治作用

[目的]探讨抗氧化剂吡咯烷二硫氨基甲酸(pyrrolidine dithiocarbamate,PDTC)对大剂量顺铂(cisplatin,DDP)所致肾毒性损伤的防治作用.[方法]昆明种小鼠100只,雌雄各半,依体重随机分为DDP组,DDP+PDTC组,生理盐水(NS)对照组.DDP 12 mg/kg单次腹腔内注射,PDTC 50 mg/kg每日皮下注射1次,连用3 d,等量NS对照.每组取10只小鼠,观察并记录其用药后的反应、体重变化及存活时间;分别取对照组小鼠和DDP用药后24、48、72 h的DDP组和DDP+PDTC组小鼠各10只,内眦静脉取血检测肾脏功能,然后剖腹取两侧肾脏,称重并计算肾系数,统计学分析. [结果]DDP用药后24 h,DDP用药组小鼠体重下降、肾系数增高;用药后48 h,小鼠血尿素氮、肌酐含量明显升高;用药72 h 66%小鼠死亡,与对照组小鼠比较差异具有显著性意义(P<0.01).PDTC可明显减轻DDP所致小鼠的体重下降,并能有效预防DDP用药后小鼠血尿素氮和肌酐的升高,明显提高小鼠的生存率,与DDP用药组小鼠比较差异具有显著性意义(P<0.01).[结论]PDTC可改善小鼠DDP用药的毒副作用,预防大剂量DDP所致的肾损伤.     

亚硒酸钠对艾氏腹水癌(实体型)生长的抑制作用

本文用“肿瘤抑制率”为指标,观察亚硒酸钠对艾氏腹水癌(实体型)生长的抑制作用。3个实验组小鼠腹腔注射亚硒酸钠,剂量分别为1/7LD_(50)(3.50mg/kg体重)、1/10LD_(50)(2.45mg/kg体重)和1/30LD_(50)(0.82mg/kg体重)每日给药1次,共7天。结果以1/10LD_(50)组的“肿瘤抑制率”为最高,经体重校正瘤重后,“肿瘤抑制率”仍高达35.59％。     

三聚氰胺及其类似物致大鼠肾结石动物模型建立

目的探讨三聚氰胺及其类似物（三聚氰酸）致肾结石动物模型的建立方法.方法雌性SD大鼠48只（167～206 g）随机分为对照组和实验组.根据每只大鼠每日进食三聚氰胺和三聚氰酸量的不同,将实验组又随机分为A、B、C三组.将计算出的每只大鼠每日进食三聚氰胺和三聚氰酸的量,溶于2 mL1%羧甲基纤维素钠内配制成混悬液予实验组灌胃,灌胃1周.对照组每日予2 mL1%羧甲基纤维素钠灌胃1周.灌胃结束时检测大鼠血肌酐、尿素氮并观察肾脏病理切片.结果给予不同剂量三聚氰胺其类似物后观察肾脏病理切片均有结晶形成,但181 mg组动物死亡率高,32 mg组结石形成率低.结论采用121 mg/（kg.day）（2 mL/day,共1周）三聚氰胺和三聚氰酸灌胃,能成功建立三聚氰胺及其类似物（三聚氰酸）肾结石动物模型.     

DEHP对新生雄性仔鼠毒性作用的实验研究

目的探讨邻苯二甲酸二乙基己基酯(DEHP)对新生雄性仔鼠毒性作用及机制。方法 DEHP分别以低、中、高3组剂量[10、100、750mg/(kg.d)]灌胃作用于怀孕12天到产后21天(GD12～PND21)的SD母鼠,观察DEHP对产后1天(PND1)及产后21天(PND21)雄性仔鼠体重、睾丸重量、肛生殖器距离(AGD)和其对胚胎Leydig细胞形态结构、促黄体生成素受体(LHR)及类固醇激素合成急性调节蛋白(StAR)的蛋白表达水平的影响。结果 PND1中、高剂量组雄仔鼠的体重下降明显,分别与对照组和低剂量组相比较均有显著性差异(P<0.01);高剂量组睾丸重量下降明显,与对照组相比较有显著性差异(P<0.05);中、高剂量组雄仔鼠的AGD均有不同程度缩短,与对照组和低剂量组相比缩短均有显著性差异(P<0.01)。PND21中、高剂量组雄仔鼠的体重下降明显,分别与对照组和低剂量组相比均有显著性差异(P<0.01);高剂量组睾丸重量下降明显,与对照组相比有显著性差异(P<0.01);中、高剂量组雄仔鼠的AGD缩短明显,分别与对照组比较有显著性差异(P<0.01)。光镜下低剂量组可见胚胎Leydig细胞(FLC)聚集呈簇分布,中剂量组与高剂量组均可见胚胎Leydig细胞呈瘤样增生。电镜示低剂量组Leydig细胞椭圆形、长梭形,脂质颗粒减少,线粒体、滑面内质网丰富。中、高剂量组Leydig细胞呈梭形或椭圆形,大小不一,核大、圆,胞质丰富,细胞聚集一起,胞质内可见丰富的脂质颗粒,脂质颗粒染色深,滑面内质网及线粒体扩张。中、高剂量组睾丸FLC的LHR蛋白表达明显减弱,与对照组比较有显著性差异(P<0.01);高剂量组睾丸FLC的StAR蛋白表达减弱明显,与对照组比较有显著性差异(P<0.01)。结论 DEHP对新生雄性仔鼠具有毒性作用,其可能机制是DEHP宫内暴露后,抑制睾丸FLC的LHR蛋白和StAR蛋白的表达从而影响睾丸的发育。     

Pathology of acute 3-acetyldeoxynivalenol toxicity in mice

Mice were killed 2, 4, 6, 12, 24, 48 and 96 hours after intragastrical administration of 0, 5, 10, 20, or 40 mg/kg body weight of 3-acetyldeoxynivalenol. The animals became clinically ill after 12 hours and some animals in the highest dose group died. Histological examination of duodenal crypts, thymus and spleen revealed, in all dose groups, presence of the characteristic lesions that are known to be produced by trichothecenes, but the intensity of lesions in the 40 mg group corresponded to lesions known to be caused by 4 mg/kg of T-2 toxin. A rabbit skin bioassay with 3-acetyldeoxynivalenol gave negative results on one occasion and a mild reaction to 100 to 500 micrograms/mL on another. It is concluded that 3-acetyldeoxynivalenol is considerably less toxic than T-2 toxin, but causes acute effects in the dividing cells of the body in a manner characteristic of trichothecenes.     

Neurobehavioral Assessment of Rats Exposed to Yttrium Nitrate during Development

Objective The aim of this study was to assess the effects of yttrium nitrate on neurobehavioral development in Sprague-Dawley rats.
Methods Dams were orally exposed to 0, 5, 15, or 45 mg/kg daily of yttrium nitrate from gestation day (GD) 6 to postnatal day (PND) 21. Body weight and food consumption were monitored weekly. Neurobehavior was assessed by developmental landmarks and reflexes, motor activity, hot plate, Rota-rod and cognitive tests. Additionally, brain weights were measured on PND 21 and 70.
Results No significant difference was noted among all groups for maternal body weight and food consumption. All yttrium-exposed offspring showed an increase in body weight on PND 21;however, no significant difference in body weight for exposed pups versus controls was observed 2 weeks or more after the yttrium solution was discontinued. The groups given 5 mg/kg daily decreased significantly in the duration of female forelime grip strength and ambulation on PND 13. There was no significant difference between yttrium-exposed offspring and controls with respect to other behavioral ontogeny parameters and postnatal behavioral test results.
Conclusion Exposure of rats to yttrium nitrate in concentrations up to 45 mg/kg daily had no adverse effects on their neurobehavioral development.     

全氟辛酸致小鼠脾脏氧化损伤的实验研究

目的:探讨不同剂量全氟辛酸(perfluorooctanoic acid, PFOA)对小鼠脾脏组织的脂质过氧化损伤效应。方法:40只SPF级ICR小鼠, 按单纯随机抽样方法分为正常对照组和低剂量组(1 mg/kg PFOA)、中剂量组(5 mg/kg PFOAS)、高剂量组(25 mg/kg PFOA)3个染毒组, 每组10只。染毒组各组每天1次灌胃相应剂量PFOA染毒, 灌胃溶液体积为0.1 ml/10 g,正常对照组给予等体积0.9%氯化钠注射液, 持续14 d, 每天称质量1次, 观察行为, 14 d后称质量处死, 计算脾脏系数, 检测脾组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、山梨醇脱氢酶(SDH)、乳酸脱氢酶(LDH)、丙二醛(MDA) 及一氧化氮(NO)水平。结果:各染毒组小鼠出现不同程度的体质量增长缓慢甚至减轻, 其中中、高剂量组出现明显减轻(P<0.01);各染毒组脾脏系数均明显高于对照组(P<0.05);与对照组相比, 各剂量组的脾组织匀浆中MDA、NO及 LDH 含量明显增高, SOD、SDH及GSH-Px 活性均明显降低(P<0.01)。结论:PFOA能抑制小鼠体质量的增长, 对脾脏组织造成一定的脂质过氧化损伤。     

对二氯苯对小鼠肝肾抗氧化功能的影响

目的:评价对二氯苯(p-DCB)亚急性染毒对小鼠的氧化性应激效应.方法:选用36只小鼠,雌雄各半,随机分成3组,每组12只,分别给予0(溶剂对照),450,900 mg/kg,每天灌胃1次,连续染毒1周.以丙二醛(MDA)作为脂质过氧化的产物指标;超氧化物歧化酶(SOD)代表抗氧化酶、还原性谷胱甘肽(GSH)代表非酶性抗氧化物综合评价氧化应激效应.结果:染毒后各组间体质量无显著性差别;染毒组肾体系数显著高于溶剂对照组(P＜0.05).小鼠肝脏及肾脏中SOD水平无显著性变化;高剂量组肾脏中GSH水平均低于对照组和低剂量组,与低剂量组比有显著性差别(P＜0.05);染毒组肝脏和肾脏中MDA水平随着染毒剂量的增加逐渐升高,高剂量组MDA水平明显高于对照组和低剂量组.结论:p-DCB能降低小鼠组织的抗氧化功能,氧化性损伤可能是其重要的毒作用机制.     

风湿平胶囊对大鼠生殖功能及胚胎发育的影响

目的:观察风湿平胶囊对大鼠生殖功能及胚胎发育的干扰和影响.方法:采用SD大鼠对风湿平胶囊进行一般生殖毒性试验.雄鼠从交配前9周至交配成功,雌鼠从交配前2周到妊娠后第8 d,连续经口灌胃给药,每天1次.交配结束后处死雄鼠,进行精子畸形检查及睾丸组织病理学检查.交配成功的雌鼠于妊娠第20 d解剖,记录胎儿总重、黄体数、着床腺数、吸收胎数、活胎数、死胎数等指标.计算雌雄大鼠交配率及妊娠率.各取一半存活胎鼠进行内脏及骨骼检查.结果:223 mg/kg、304 mg/kg、446 mg/kg、608 mg/kg的风湿平胶囊可导致雄性大鼠睾丸生精细胞发育不良、精子减少及精子畸形等.1216 mg/kg的风湿平胶囊可致雌鼠体重增长缓慢,304 mg/kg以上剂量的风湿平胶囊可降低雌性大鼠妊娠率,608 mg/kg和1216 mg/kg的风湿平胶囊可降低雌鼠黄体数及着床腺数,1216 mg/kg的风湿平胶囊可致胎鼠骨骼发育迟缓.结论:风湿平胶囊可导致雄鼠睾丸生精细胞发育不良、精子减少及精子畸形等,影响雌鼠受精卵着床及引起胎鼠骨骼发育缓慢.