锌、硒对镉中毒小鼠金属硫蛋白合成及脂质过氧化损伤的影响

目的 观察锌、硒对镉中毒小鼠金属硫蛋白合成及脂质过氧化的影响,为镉中毒的研究及防治提供理论基础. 方法 36只昆明小鼠随机分成6组,每组6只:对照组,经口灌注生理盐水;CdCl2组,100 μmol/kg的CdCl2,经口灌胃;Zn2SO4组,Zn2SO4 20 μmol/kg经口灌胃;Na2SeO3组,Na2SeO3 10 μmol/kg经口灌胃;CdCl2+Zn2SO4组,Zn2SO4和CdCl2交替经口灌胃;CdCl2+Na2SeO3组,Na2SeO3和CdCl2交替经口灌胃.109Cd-血红素饱和法测小鼠组织金属硫蛋白含量;试剂盒检测小鼠组织丙二醛(MDA)含量及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性. 结果 单独镉、锌、硒组及Zn+Cd、Se+Cd组小鼠肝、心和肾脏MT含量均明显高于对照组,CdCl2组小鼠肝、心和肾脏MDA含量增高、SOD和GSH-Px活力降低.CdCl2+Zn2SO4组和CdCl2+Na2SeO3组小鼠肝、心和肾脏MT含量较单用CdCl2组进一步增高(P<0.05),MDA含量降低,SOD和GSH-Px活力升高. 结论 锌、硒增加镉中毒小鼠金属硫蛋白合成,减轻镉中毒小鼠脂质过氧化损伤.     

大鼠慢性砷中毒生精细胞XRCC_1蛋白表达与凋亡

目的:研究大鼠不同剂量慢性砷中毒生精细胞XRCC1蛋白表达水平和凋亡变化及其相互作用。方法:将40只健康雄性SD大鼠随机分为对照、低剂量、中剂量和高剂量4组,每组10只。以灌胃方式分别给予双蒸水、0.375mg/kgAs2O3水溶液、0.75mg/kgAs2O3水溶液、1.5mg/kgAs2O3水溶液,每日1次,连续给药16周。取睾丸组织免疫组化法检测其睾丸XRCC1蛋白表达、TUNEL检测细胞凋亡。结果:大鼠生精细胞XRCC1蛋白表达低剂量组与对照组无显著性差异(P>0.05);中、高剂量组XRCC1蛋白的表达较对照组降低(均P<0.05),XRCC1蛋白表达量随着染毒剂量的增高而降低(r=-0.637,P<0.001)。生精细胞凋亡指数低剂量组与对照组无显著性差异(P>0.05);中、高剂量组均高于对照组(P<0.05),且随着染毒剂量的增高而升高(r=0.893,P<0.001)。XRCC1蛋白表达与生精细胞凋亡指数呈负相关关系(r=-0.738,P<0.001)。结论:慢性接触0.75mg/kg和1.5mg/kgAs2O3可诱导SD大鼠生精细胞凋亡增加,XRCC1蛋白的表达降低可能是导致大鼠生精细胞凋亡增加原因之一。     

高脂膳食、硒对大鼠抗氧化功能的影响

目的 探讨在高脂膳食模式、不同安全剂量的硒暴露情况下,硒对大鼠抗氧化功能的影响.方法 选取SPF级Wistar大鼠60只,6周龄,雌雄各半,采用完全随机化法分为普通组、普通+0.3 mg/kg Se组、普通+0.9 mg/kg Se组、高脂组、高脂+0.3 mg/kg Se组和高脂+0.9 mg/kg Se组,每组10...     

三七总皂苷联合环磷酰胺对荷肝癌H22细胞移植瘤小鼠的治疗作用

目的 探究三七总皂苷（PNS）联合环磷酰胺（CTX）对肝癌H22荷瘤小鼠的治疗作用。方法 不同浓度的PNS体外干预肝癌H22细胞24~72 h后,CCK8比色法检测PNS对肝癌H22细胞增殖的影响;Annexin V/PI双荧光染色法检测PNS对肝癌H22细胞凋亡的影响;体内构建肝癌H22荷瘤小鼠模型,随机分为模型组、CTX组（25 mg/kg）、PNS低剂量组（120 mg/kg）、PNS中剂量组（240 mg/kg）、PNS 高剂量组（480 mg/kg）及 PNS 低剂量+CTX 组（120 mg/kg+25 mg/kg）、PNS 中剂量+CTX 组（240 mg/kg+25 mg/kg）、PNS高剂量+CTX组（480 mg/kg+25 mg/kg）,连续给药10 d后处死小鼠,取材,检测PNS及PNS联合CTX对肝癌H22荷瘤小鼠单核-巨噬细胞的吞噬能力、脾淋巴细胞增殖能力、肿瘤坏死因子（TNF-α）、白介素-2（IL-2）的水平、血清溶血素抗体水平、血液指标、抑瘤率和生存期的影响。结果 PNS对肝癌 H22细胞的增殖抑制呈浓度依赖性,能显著促进肝癌H22细胞的凋亡（P<0.01）。体内单用PNS及PNS联合CTX能增强单核-巨噬细胞的吞噬、刺激脾淋巴细胞的增殖、促进TNF-α、IL-2释放、促进血清溶血素抗体的生成,增加外周血中白细胞、红细胞、淋巴细胞的数量,PNS高剂量+CTX组的抑瘤率高达83.28%（P<0.01）、生命延长率达131.25%（P<0.05）。结论 PNS及PNS与CTX联用可提高机体的免疫力和抑瘤率,延长肝癌H22荷瘤小鼠的生存期。     

As2O3对人子宫内膜癌细胞HEC-1-B皮下移植瘤抗肿瘤作用

目的 检测不同浓度As2O3对人子宫内膜癌HEC-1-B细胞裸鼠皮下移植瘤的抗肿瘤作用及对瘤细胞内磷酸化细胞外信号调节蛋白激酶(p-ERK)表达的影响,进一步探讨As2O3的抗肿瘤机制.方法 建立人子宫内膜癌HEC-1-B细胞皮下移植瘤模型,随机分为实验组,即As2O3低剂量(1.0 mg/kg)、中剂量(2.5 mg/kg)、高剂量(5.0 mg/kg)剂量组,生理盐水(NS)组及顺铂组(5 mg/kg),腹腔内注射给药,连续8 d.观察用药前后裸鼠体质量改变.剥取瘤组织,计算药物的抑瘤率.检测用药后裸鼠的肝肾功能及血常规.透射电镜观察细胞变化,流式细胞仪检测细胞凋亡周期和细胞凋亡率,免疫组化法检测p-ERK的表达.结果 不同浓度As2O3和顺铂均有不同程度抑制肿瘤细胞生长、促进肿瘤细胞凋亡的作用,其中As2O3低剂量组的抑瘤率为34.3%,p-ERK的表达率为37.5%,该组在亚G1期出现典型的凋亡峰,且As2O3低剂量组与NS组比较,凋亡率、瘤质量差异均有显著意义(F=27.20、33.92,q=9.19、13.34,P<0.05).As2O3低剂量组与顺铂组相比,无明显血液及肝肾毒性.结论 低剂量As2O3组能明显抑制肿瘤细胞HEC-1-B生长,且毒副作用轻,可能与阻滞细胞周期,抑制p-ERK表达有关.     

丹参素异丙酯对D-半乳糖致衰老大鼠肾脏的保护作用

目的:探讨丹参素异丙酯(IDHP)对D-半乳糖(D-gal)致衰老大鼠肾脏组织的保护作用。方法:40只Wistar大鼠分为空白对照组、衰老模型组、维生素E(VE,100.0 mg/kg)组、高剂量IDHP(21.0 mg/kg)组和低剂量IDHP(7.0 mg/kg)组5组,每组8只。后4组大鼠皮下注射25 g/L D-gal 2 mL/(kg·d)制作衰老大鼠模型,VE组、高剂量IDHP组和低剂量IDHP组大鼠皮下注射相应浓度的药物2 mL/kg, 1次/d,连续8周。计算各组大鼠肾脏指数,HE染色观察肾脏组织细胞形态变化,检测血清肌酐、尿素水平,肾脏组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)活性及丙二醛(MDA)和过氧化脂质(LPO)水平。结果:与衰老模型组相比,VE组、高剂量IDHP组和低剂量IDHP组大鼠肾脏指数升高;与低剂量IDHP组相比,VE组、高剂量IDHP组大鼠肾脏指数升高(P<0.05)。衰老模型组大鼠肾脏组织呈现典型衰老性病理改变,VE组、高剂量IDHP组、低剂量IDHP组均有改善,但VE组、高剂量IDHP组改善更为...     

甘草甜素对周围神经损伤模型大鼠神经再生的干预效果及其可能机制

目的探讨甘草甜素对周围神经损伤模型大鼠的干预效果及其可能机制。方法选取50只SD健康雄性大鼠,建立周围神经损伤模型,随机分为对照组、模型组、低剂量、中剂量、高剂量组各10只。低、中、高剂量组大鼠分别给予10 mg/kg、20 mg/kg、30 mg/kg甘草甜素溶液灌胃,对照组、模型组大鼠灌胃等体积生理盐水。检测各组大鼠有髓神经纤维直径和数量,计算比目鱼肌肌肉指数;并检测脊髓组织生长相关蛋白43(GAP-43)、神经营养因子受体p75(p75NTR)蛋白表达水平,T、B淋巴细胞增殖率,神经元细胞凋亡率。结果模型组、低剂量组、中剂量组、高剂量组、对照组大鼠脊髓GAP-43相对表达量依次升高,p75NTR相对表达量依次降低,比目鱼肌肌肉指数及有髓神经纤维直径、数量依次升高(P<0.05);各个时间段,模型组、低剂量组、中剂量组、高剂量组、对照组大鼠T、B淋巴细胞增殖率、神经元细胞凋亡率依次降低(P<0.05)。结论甘草甜素可能通过调控GAP-43、p75NTR蛋白的表达,来抑制周围神经损伤模型大鼠T、B淋巴细胞增殖以及神经元细胞凋亡,从而促进周围神经再生,减轻比目鱼肌萎缩程度。     

消渴康复颗粒对糖尿病肾病大鼠肾脏损伤的保护作用研究

目的 探讨消渴康复颗粒对糖尿病肾病（DN）大鼠肾脏损伤的保护作用。方法 取50只SD大鼠,采用高糖高脂饲料喂养及35 mg/kg链脲佐菌素于尾部静脉注射建立DN模型,依据随机数字法将其分为模型组、消渴康复颗粒低剂量组（128.57 mg/kg）、中剂量组（257.14 mg/kg）、高剂量组（514.29 mg/kg）及阳性对照组（厄贝沙坦混悬液25 mg/kg）各10只,另外10只正常大鼠作为正常对照组,经尾部静脉注射生理盐水。干预8周后,比较各组大鼠相关生化指标和肾脏指数情况,观察SD大鼠肾脏组织的病理改变、细胞DNA损伤情况以及肾脏组织张力蛋白同源基因（PTEN）、蛋白激酶B(AKT)、雷帕霉素靶蛋白（m TOR）蛋白表达。结果 与正常对照组比较,模型组SD大鼠肾细胞胞质肿胀,细胞膜破裂,胞核固缩断裂增多,空腹血糖、尿微量白蛋白与尿肌酐比值（UACR）、尿素氮（BUN）、肾脏指数、阳性细胞数量及PTEN蛋白表达水平升高,AKT、mTOR蛋白表达水平降低,差异均有统计学意义（P均<0.05）。与模型组比较,消渴康复颗粒低剂量、中剂量、高剂量组及阳性对照组肾小管上皮细胞有较好的...     

长期低剂量锰染毒对子代大鼠睾丸生精细胞线粒体状态和细胞凋亡的影响

目的 探讨长期低剂量氯化锰染毒对子代大鼠睾丸生精细胞线粒体形态和凋亡的影响.方法 健康雌性SD大鼠32只分为对照组、低、中、高剂量组.腹腔注射2、4和8 mg/kg MnCl2·4H2O或生理盐水,1次/天,5天/周,共8周,并在妊娠期和哺乳期继续染毒.每组8只12周龄子代大鼠断头处死后,观察睾丸生精小管结构和生精细胞线粒体形态、视神经萎缩蛋白1(Opa1)、动力相关蛋白1(Drp1)、半胱氨酸蛋白酶9(Caspase9)表达和细胞凋亡情况.结果 随锰染毒剂量增加,生精细胞层数逐渐减少,细胞排列紊乱、数量减少;中、高剂量组可见线粒体分离、肿胀等表现;中、高剂量组Opa1显著降低(P＜0.05,P＜0.01),Drp1、Caspase9则随锰染毒剂量增加而递增(P＜0.05,P＜0.01);锰染毒组生精细胞凋亡指数随锰染毒剂量增加而上升(P＜0.05).结论 长期低剂量锰染毒可调节Opa1/Drp1基因表达而影响线粒体功能,导致子代大鼠生精细胞凋亡.     

六味地黄汤对糖尿病肾病大鼠肾功能及细胞凋亡的影响

目的 探讨六味地黄汤对糖尿病肾病 (DN) 大鼠肾脏功能保护作用的量效关系及对细胞凋亡的影响。方法采用单侧肾脏结扎术+腹腔注射链脲佐菌素 (STZ) 的方法建立 DN 模型2周实验结束时测定大鼠血糖、肌酐清除率、尿蛋白定量;2、4、8周实验结束时分析大鼠肾皮质细胞 DNA 降解的琼脂糖凝胶电泳,TUNEL 法观察大鼠肾皮质细胞凋亡发生的部位,流式细胞仪测定细胞凋亡率。结果2周实验结束时,3个剂量给药组均可不同程度降低 DN 大鼠血糖,减少尿蛋白的排泄,有效降低肌酐清除率;中、低剂量间显示出一定的量效关系,中剂量 24.96 g/kg 作用最佳;模型组大鼠 8 周时肾皮质细胞 DNA 琼脂糖凝胶电泳可出现 100～300 bp 的条带。TUNEL 法检测模型组肾皮质细胞凋亡提示,2周时凋亡极少发生,4周时凋亡明显增多,多数在远端肾小管,8周时除远端肾小管外,近端肾小管亦可见散在的凋亡细胞,但肾小球未见凋亡细胞。流式细胞仪分析各组细胞凋亡率,4周及8周时 DN 模型大鼠存在肾脏皮质细胞凋亡率增加,给药组与之相比细胞凋亡率显著下降。结论 六味地黄汤干预 DN 大鼠2周后,可以显著降低血糖、减少尿蛋白排泄量、改善肌酐清除率,从而起到保护 DN 大鼠肾功能的作用,24.96 g/kg 为最佳剂量,六味地黄汤可以通过抑制 DN 大鼠肾皮质细胞凋亡来改善 DN 肾脏病理变化。     

Effects of Selenium and Zinc on Renal Oxidative Stress and Apoptosis Induced by Fluoride in Rats

To study the effects of selenium and zinc on oxidative stress, apoptosis, and cell cycle changes in rat renal cells induced by fluoride. Methods Wistar rats were given distilled water containing sodium fluoride (50 mg/L NaF) and were gavaged with different doses of selenium-zinc preparation for six months. Four groups were used and each group had eight animals (four males and four females). Group one, sham-handled control; group two, 50 mg/L NaF; group three, 50 mg/L NaF with a low dose of selenium-zinc preparation (0.1 mg/kg Na2 SeO3 and 14.8 mg/kg ZnSO4·7H2O); and group four, 50 mg/L NaF with a high dose of selenium-zinc preparation (0.2 mg/kg Na2 SeO3 and 29.6 mg/kg ZnSO4·7H2O). The activities of serum glutathione peroxidase (GSH-Px), kidney superoxide dismutase (SOD), and the levels of malondialdehyde (MDA) and glutathione (GSH) in the kidney were measured to assess the oxidative stress. Kidney cell apoptosis and cell cycle were detected by flow cytometry. Results NaF at the dose of 50 mg/L increased excretion of fluoride in urine, promoted activity of urineγ-glutamyl transpeptidase (γ-GT), inhibited activity of serum GSH-PX and kidney SOD, reduce kidney GSH content, and increased kidney MDA. NaF at the dose of 50 mg/L also induced rat renal apoptosis, reduced the cell number of G2/M phase in cell cycle, and decreased DNA relative content significantly. Selenium and zinc inhibited effects of NaF on oxidative stress and apoptosis, promoted the cell number of G2/M phase in cell cycle, but failed to increase relative DNA content significantly. Conclusion Sodium fluoride administered at the dose of 50 mg/L for six months induced oxidative stress and apoptosis, and changes the cell cycle in rat renal cells. Selenium and zinc antagonize oxidative stress, apoptosis, and cell cycle changes induced by excess fluoride.     

硒镉联合作用的不同染毒方式研究

目的研究亚硒酸钠和氯化镉在联合作用时的不同染毒方式。方法检测亚硒酸钠和氯化镉在同时经口染毒时肝肾组织中的硒、镉含量以及同时腹腔注射染毒时镉在肝组织中的含量和在肝细胞器中的分布。结果经口染毒时，氯化镉对低剂量硒染毒时肝肾组织中的硒含量无明显影响，低剂量硒在实验早期可使肝肾组织中的镉含量增高，在实验后期又使肝肾组织中的镉含量下降，高剂量的亚硒酸钠和氯化镉彼此降低其在肝肾组织中的含量。腹腔注射染毒时亚硒酸钠对氯化镉在肝组织中的含量以及在肝细胞器中的分布没有明显影响。结论经口或腹腔注射同时染毒亚硒酸钠和氯化镉仍不失为研究硒镉联合作用的适宜染毒方式。为了避免硒镉形成复合物和硒镉彼此影响吸收，采用经口和腹腔注射的混合染毒方式，值得推荐。     

Inhibitory effects of grape seed proanthocyanidin extract on selenite-induced cataract formation and possible mechanism

This study investigated the inhibitory effect of grape seed proanthocyanidin extract(GSPE) on selenite-induced cataract formation in rats and the possible mechanism.Eighty 8-day-old Sprague-Dawley rats were divided randomly into 5 groups:control group,model group,three GSPE groups(low dose,medium dose and high dose).Control group received subcutaneous injection of physiological saline.Model group was given subcutaneous injection of sodium selenite(20 μmol/kg body weight) on the postpartum day 10,and once every other day for consecutive three times thereafter.GSPE treated groups were respectively administered GSPE at doses of 50,100,and 200 mg/kg body weight intragastrically 2 days prior to the selenite injection(that was,on the postpartum day 8),and once daily for fourteen consecutive days thereafter.The opacity of lenses was observed,graded and photographed under the slit lamp microscopy and the maximal diameter of the nuclear cataract plaques was measured.The lenses were analyzed for superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-PX),malondialdehyde(MDA),calcium(Ca 2+),nitric oxide(NO) and anti-hydroxyl radical ability(anti-OH).The histomorphology of lenses was observed with HE staining under a light microscope.The levels of calpainⅡ,and iNOS protein and mRNA expression in lenses were detected by using immunohistochemistry and real-time quantitative RT-PCR.The results showed subcutaneous injection of sodium selenite led to severe nuclear cataract in model group,and the achievement ratio of model group was 100%.As compared with model group,the degree of lenses opacity and the maximal diameter of nuclear cataract plaques were significantly reduced in GSPE-treated groups.Moreover,we observed selenite treatment caused a significant decrease in the activities of antioxidative enzymes(SOD,CAT,GSH-PX) and anti-OH ability,accompanied by a significant increase in the levels of MDA,NO,Ca 2+ as well as iNOS,and calpainⅡ protein and mRNA expression.Administration of GSPE could dose-dependently pre     

Zinc in CCl4 toxicity

Objective To investigate the protective effect of zinc in CCl4-induced hepatotoxicity. Methods Rats were treated with zinc acetate for four days. The zinc doses were 5 mg Zn/kg and 10 mg Zn/kg body weight respectively. Two groups of the zinc acetate-treated rats were later challenged with a single dose of CCl4 (1.5 mL/kg body weight). Results Compared to control animals, the plasma of rats treated with CCl4 showed hyperbilirubinaemia, hypoglycaemia, hypercreatinaemia and hypoproteinaemia. When the animals were however supplemented with zinc in form of zinc acetate before being dosed with CCl4, the 5 mg Zn/kg body weight of zinc acetate reversed the hypoproteinaemia induced by CCl4, whereas the 10mg Zn/kg body weight of zinc acetate reversed the hypoglycaemia, hyperbilimbinaemia and hypercreatinaemia induced by CCl4. Conclusion The 10mug Zn/kg body weight of zinc acetate is more consistent in protecting against CCl4 hepatotoxicity. The possible mechanisms of protection are highlighted.     

植酸钠对饮食所致高脂血症大鼠心血管的保护作用

目的研究植酸钠对饮食所致高脂血症大鼠心血管保护作用机制。方法5周龄的Wistar大鼠按体重随机分成4组：正常饮食组（对照组）、高脂饮食组（高脂模型对照组）、高脂饮食＋100mg／kg植酸钠（高剂量植酸钠组）、高脂饮食＋50mg／kg植酸钠（低剂量植酸钠组）。4周后测定各组大鼠血脂、氧化应激、心肌瘦素、心肌Na^＋，K^＋-ATPase和Ca^2＋，Mg^2＋-ATPase酶水平。结果与对照组相比，高脂血症显著提高血清总胆固醇、甘油三脂、高密度脂蛋白、低密度脂蛋白的含量，提高血清丙二醛（MDA）水平，显著降低血清超氧化物岐化酶（SOD）、谷胱甘肽过氧化物酶（GSH—Px）、过氧化氢酶（CAT）3种抗氧化酶水平，降低心肌Na^＋，K^＋-ATPase、Ca^2，Mg^2＋-ATPase和瘦素水平；高剂量或低剂量植酸钠组均可显著升高血清SOD、GSH—Px、CAT抗氧化酶水平，增高心肌Na^＋，K^＋-ATPase、Ca^2＋，Mg^2＋-ATPase水平，降低MDA含量，但对血脂水平无显著影响。高剂量植酸钠组还可显著增加心肌瘦素水平。结论植酸钠具有心血管保护作用，其作用机制至少包括抗氧化作用和增加心肌细胞的瘦素表达两个方面。     

Role of reactive oxygen species in triptolide-induced apoptosis of renal tubular cells and renal injury in rats

This study investigated the role of reactive oxygen species(ROS) in the pathogenesis of triptolide-induced renal injury in vivo.Rats were randomly divided into 4 groups(n=5 in each):triptolide group in which the rats were intraperitoneally injected with triptolide solution at a dose of 1 mg/kg of body weight on day 8;control group in which the rats received a single intraperitoneal injection of 0.9% physiological saline on day 8;vitamin C group in which the rats were pretreated with vitamin C by gavage at a dose of 250 mg/kg of body weight per day for 7 days before the same treatment as the control group on day 8;triptolide+vitamin C group in which the rats were first subjected to an oral administration of vitamin C at a dose of 250 mg/kg of body weight per day for 7 days,and then to the same treatment as the triptolide group on day 8.All the rats were sacrificed on day 10.Blood samples were collected for detection of plasma creatinine(Pcr) and plasma urea nitrogen(PUN) concentrations.Both kidneys were removed.The histological changes were measured by haematoxylin-eosin(HE) staining.The production of ROS was determined by detecting the fluorescent intensity of the oxida-tion-sensitive probe rhodamine 123 in renal tissue.Renal malondialdehyde(MDA) content was meas-ured to evaluate lipid peroxidation level in renal tissue.TUNEL staining was performed to assess apop-tosis of renal tubular cells.Renal expression of apoptosis-related proteins Bcl-2,Bax,Bid,Bad,Fas and FasL,as well as corresponding encoding genes were assessed by Western Blotting and real-time PCR.The results showed that triptolide treatment promoted the generation of a great amount of ROS,up-regulated the expression of Bax,Bid,Bad,Fas and FasL at both protein and mRNA levels,as well as the ratio of Bax to Bcl-2,and caused the apoptosis of renal tubular cells and renal injury.However,pretreatment with an antioxidant,vitamin C,significantly reduced the generation of ROS and effectively inhibited the triptolide-induced apoptosis of renal tubular cells and renal injury.It was concluded that ROS plays a critical role in triptolide-induced apoptosis of renal tubular cells and renal injury.The protective administration of vitamin C may help alleviate triptolide-induced renal injury and nephrotoxicity.     

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％。     

产前糖皮质激素应用对胎鼠脑发育的影响

目的:探讨产前应用不同剂量糖皮质激素(antenatal corticorsteriod theray,ACT)对胎鼠脑发育的影响.方法:对怀孕第17天的SD大鼠每天肌注地塞米松0.8 mg/kg,肌注1次的为1剂组、肌注3次的为3剂组和肌注4次的为4剂组,没有使用地塞米松的为对照组.对各组孕鼠所生的胎鼠,分别于生后第1、第7和第14天测量体重、全脑重量、脑细胞凋亡情况并与对照组作比较.结果:实验组胎鼠的体重、全脑重量较对照组明显下降,尤以4剂组最明显;脑细胞凋亡数3剂组、4剂组与对照组在第1天有差别,第7天和第14天差别减弱.结论:ACT对胎鼠的体重、全脑重量、脑细胞凋亡等产生不良影响,剂量越大副作用越明显.     

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.     

Absorption and metabolism of paracetamol in rats drinking high concentration of arsenic

The effect of chronic intake of arsenic on the plasma concentration of paracetamol in rat was investigated. Rats received saline water with or without arsenic trioxide (10 mg/kg body weight/day) by gastric gavage on every alternate day for 29 days. A single dose of paracetamol (range 10 infinity 40 mg/kg body weight) was administered by gastric gavage to both arsenic-untreated and -treated rats on 30(th) day. Rats were sacrificed after 30 min and the amounts of free paracetamol and its metabolites in plasma were estimated using isocratic reverse-phase High Performance Liquid Chromatography (HPLC). Arsenic toxicity reduced the plasma concentration of paracetamol to 53 - 65% when compared with the rats received no added arsenic. There were maximum 67.4 and 76.9% inhibitions of sulfate and cysteine conjugations of paracetamol respectively. But arsenic had no effect on glucuronide and mercapturate conjugations. Both liver and small intestine showed increased accumulation of arsenic and decreased amount of glutathione in arsenic-treated rats. This study suggests that chronic ingestion of arsenic inhibit the absorption and metabolism of paracetamol.