益气活血中药的毒性实验研究

目的 观察益气活血中药对正常小鼠的毒性作用.方法 取健康小鼠120只,随机分为78 g/kg剂量组、156 g/kg剂量组、312 g/kg剂量组和对照组,每组30只.不同剂量组分别予相应剂量益气活血中药灌胃,对照组予0.9%氯化钠注射液灌胃.观察不同组用药前,给药1、2、3个月及停药后2周一般情况,并于给药后3个月及停药后2周采血测定血液学及生化指标,同时对其肝、肾和胃等组织结构进行病理学检查.结果 给药期间不同剂量组和对照组一般情况均未发现异常.给药前,给药1、2、3个月及停药后2周不同剂量组体重与对照组比较差异均无统计学意义(P＞0.05).给药后3个月及停药后2周,不同剂量组血液学及生化指标与对照组比较差异亦均无统计学意义(P＞0.05);处死小鼠病理学检查结果示心、肝、脾、肺、肾、胃、小肠及性腺等组织结构均未发现明显异常.结论 益气活血中药口服安全,长期使用无毒副作用.     

益气活血中药的毒性实验研究

目的 观察益气活血中药对正常小鼠的毒性作用.方法 取健康小鼠120只,随机分为78 g/kg剂量组、156 g/kg剂量组、312 g/kg剂量组和对照组,每组30只.不同剂量组分别予相应剂量益气活血中药灌胃,对照组予0.9%氯化钠注射液灌胃.观察不同组用药前,给药1、2、3个月及停药后2周一般情况,并于给药后3个月及...     

风痛宁丸对大鼠的长期毒性试验

目的：观察大鼠长期使用风痛宁丸的毒性反应及其程度,评价其安全性。方法：健康Wistar大鼠随机分低、中、高剂量（1g生药·kg^-1,4g生药·kg^-1,8g生药·kg^-1）组及蒸馏水对照组,每组20只,灌胃给药,qd,连续给药3个月,检测血液学、血液生化、脏器系数及组织病理学改变。结果：连续3个月对大鼠灌胃给药及停药2周,与灌胃蒸馏水的空白对照组比较,各剂量组给药对大鼠的一般状态、体重、造血功能、肝肾功能和重要器官重量系数,均未发现明显毒性作用;病理学检查大鼠心、肝、脾、肺、肾、胸腺、肾上腺等器官组织均未发现有明显毒性损伤变化。结论：风痛宁丸较大剂量和较长疗程服用毒性甚低,服用较安全。     

整肠丸的长期毒性研究

目的：研究整肠丸在 SD 大鼠的长期毒性。方法：将 120 只 SD 大鼠随机分为高剂量组（3.96 g/kg）、中剂量 组（1.98 g/kg）、低剂量组（0.99 g/kg）和阴性对照组,每组 30 只。采用经口灌胃给药法,每日一次,每周 6 天, 连续给药 3 个月,并停药 2 周作恢复性观察。试验期间每日观察一般状况,每周称重和记录摄食量,分别在实验结 束和停药恢复期测定大鼠的脏器系数、血液生理生化指标和组织病理学变化。结果：给药 3 个月后各组大鼠一般状 态和组织病理学检查无明显异常;各给药组体重、摄食量、脏器系数与对照组比较无显著性差异（P＞0.05）;给药 期血常规指标和血生化指标与对照组比较,少部分指标有显著性差异（P＜0.05）,恢复期无显著性差异。结论：以 人体推荐量的 60 倍、30 倍、15 倍对 SD 大鼠进行 3 个月喂养试验,整肠丸对少部分 SD 大鼠血液生理生化指标有影响, 停药 2 周后可恢复。     

蟾砂胶囊急性与长期毒性研究

目的探讨蟾砂胶囊单次或多次给药后,动物出现的毒性反应及其性质和程度,为临床安全用药提供毒理学依据。方法急性毒性实验采用小鼠灌胃给予蟾砂胶囊浸膏10.8g/kg体重(分2次),观察14d;长期毒性实验采用大鼠连续以蟾砂胶囊19.98g/kg、9.99g/kg、2.00g/kg体重,灌胃给药180d,停药30d,观察其雌雄大鼠体重、食量及粪便等一般临床体征,检测血液学指标、血液生化指标、脏器指数,并对主要器官和组织进行了病理学观察。结果小鼠灌胃最大耐受量为45.8g生药/kg,相当临床用量的92.3倍。长期毒性试验中,中、高剂量组对血液学指标,高剂量组对血液生化学指标、脏器重量绝对值、脏器指数等出现一定的影响,部分指标有显著差异(P<0.01),脏器肉眼观察及病理学检查可见肝脏和肾脏有病理改变。停药恢复30d后,大鼠体重、摄食量、活动、血液学、生化指标检查、脏器重量系数、病理学检查均正常。结论蟾砂胶囊在说明书推荐剂量下服用是安全可靠的。     

养阴益气胶囊长期毒性实验

目的 评价养阴益气胶囊对大鼠灌胃给药6个月的长期毒性情况。方法 90只SD大鼠随机分为3组：养阴益气胶囊大剂量组(每日灌胃给药剂量相当于生药20 g·kg^-1)、养阴益气胶囊小剂量组(每日灌胃给药剂量相当于生药5 g·kg^-1)和空白对照组(每日灌胃等容量纯化水),灌胃容量均为5 mL·kg^-1,给药时间均为180 d。观察指标为大鼠外观体征、进食、行为活动、排便、体质量、血液学及血生化指标,以及病理检查。停药后继续进行可逆性观察2周。结果 小剂量组和大剂量组大鼠体质量增加,但稍低于空白对照组(P>0.05);两组大鼠血液学指标均在正常范围内,与空白对照组之间差异无统计学意义(P>0.05);大剂量组血尿素氮高于空白对照组(P<0.05),但仍在正常范围内,其余血生化指标各组间差异无统计学意义(P>0.05)。各组动物系统尸解、组织病理学检查及可逆性观察均未见异常,脏器系数及生殖腺系数组间差异均无统计学意义(P>0.05)。结论 养阴益气胶囊给大鼠灌胃给药6个月的安全剂量为相当于生药20 g...     

伸筋活血合剂安全性评价实验

目的:通过伸筋活血合剂的小鼠急性毒性实验以及大鼠长期毒性实验,考察其安全性,为临床用药提供依据。方法:取昆明种小鼠40只,随机分为2组,即用药组(240 g生药/kg)和对照组(生理盐水),一次性灌胃给药,连续14 d观察小鼠的活动、体重变化及死亡情况等。取大鼠80只,随机分为4组,即伸筋活血合剂高、中、低剂量组(60、216、g生药/kg)和对照组,每组20只,每天灌胃给药一次,每周按体重变化调整给药量,连灌60 d。每次给药前后观察大鼠,在第60天给药后24 h以及停药观察3周后分别每组随机处死10只大鼠(雌雄各半),检测血液学及血生化的各项指标并进行组织病理学检查。结果:小鼠急性毒性实验未测出半数致死量(LD50),最大耐受量为240 g/kg,相当于临床日用量的160倍。大鼠连续60 d灌胃给药后及停药3周后,各剂量给药组与同时间对照组大鼠比较,一般状态,体重,摄食量,造血功能,肝、肾功能和重要器官重量系数,均未发现明显毒性作用;组织病理学检查显示,大鼠心、肝、脾、肺、肾等器官组织也未发现明显毒性损伤变化。结论:服用伸筋活血合剂较大剂量和较长疗程毒性甚低,其日服剂量1.5 g生药/kg,确定为无毒性反应剂量,是安全可靠的。     

康炎净颗粒对大鼠长期毒性试验研究

目的观察连续灌胃给予康炎净颗粒对大鼠产生的毒性反应。方法将160只雌性大鼠随机分为空白对照组(对照组)、康炎净颗粒低剂量组(低剂量组,9. 69 g/kg)、康炎净颗粒中剂量组(中剂量组,28. 77g/kg)和康炎净颗粒高剂量组(高剂量组,85. 44 g/kg),每组40只,每天给药1次,连续给药6个月,停药4周,观察给药中、末期及停药恢复期大鼠的一般状况,称量大鼠体重,计算脏器系数,测定主要血液学指标、生化学指标,并进行脏器组织病理学检查。结果高剂量组于给药第1周开始,体重、摄食量均明显低于空白对照组,并在12周出现死亡现象。给药3个月后,高剂量组大鼠红细胞计数、血红蛋白、红细胞压积、肌酐明显低于对照组(P <0. 05);平均血细胞容积、网织红细胞百分率、白细胞计数、中性粒细胞比率,血清尿素氮、血清钾,肝、脾、肾、肾上腺脏器指数明显高于对照组(P <0. 05)。给药6个月后,高剂量组大鼠红细胞计数、血红蛋白、红细胞压积、肌酸激酶明显低于对照组(P <0. 05),平均血细胞容积,平均血红蛋白含量,网织红细胞百分率,肝、脾、肾脏器指数明显高于对照组。停药4周后,高剂量组大鼠红细胞计数、血红蛋白、红细胞压积明显低于空白对照组(P <0. 05);网织红细胞百分率,肝、脾、肾脏器指数明显高于对照组(P <0. 05)。结论康炎净颗粒大鼠灌胃给药安全剂量为28. 77 g/kg以下,约为临床成人拟用量的22. 27倍(成人按60 kg计)。     

滋阴补肾丸的毒理学研究

目的:观察动物对滋阴补肾丸的急性及长期毒性反应,为临床用药安全剂量提供参考.方法:①昆明种小鼠40只,随机分成给药和对照组2组.②Wistar大鼠160只,随机分成4组,每天2次灌胃给药,连续灌胃26周.观察一般情况,并进行病理学检查,检测血常规、生化及血凝指标等.结果:滋阴补肾丸的毒性较低,1次最大给药量为63.9 g/kg,1日最大给药量为191.7 g/kg.长期灌胃此药,大鼠体重、脏器、血液学指标和病理组织学检测均未见异常.结论:滋阴补肾丸是一种安全、毒性低的药物.     

滋阴补肾丸的毒理学研究

目的:观察动物对滋阴补肾丸的急性及长期毒性反应,为临床用药安全剂量提供参考.方法:①昆明种小鼠40只,随机分成给药和对照组2组.②Wistar大鼠160只,随机分成4组,每天2次灌胃给药,连续灌胃26周.观察一般情况,并进行病理学检查,检测血常规、生化及血凝指标等.结果:滋阴补肾丸的毒性较低,1次最大给药量为63.9 g/kg,1日最大给药量为191.7 g/kg.长期灌胃此药,大鼠体重、脏器、血液学指标和病理组织学检测均未见异常.结论:滋阴补肾丸是一种安全、毒性低的药物.     

抗衰片对电离辐射损伤后小鼠骨髓造血作用的影响

摘要： 目的 探讨抗衰片对电离辐射损伤后小鼠造血重建的调控影响。方法 9~10 周龄雄性 C57BL/6 小鼠随机分为照射对照组、 低剂量组、 中剂量组和高剂量组, 每组 10 只。后 3 个剂量组分别按 0.75、 1.5、 3.0 g/kg 体质量灌服抗衰片水溶液, 照射对照组给予同体积生理盐水, 1 次/d, 连续给药 11 d。第 4 天对 4 组小鼠进行 6.0 Gy 137 Cs-γ射线单次全身照射。照射后第 8 天, 观察小鼠内源性脾结节 （即脾集落形成单位, CFU-S）、 小鼠骨髓粒-巨噬细胞集落形成单位 （CFU-GM） 和骨髓成纤维细胞集落形成单位 （CFU-F） 的生成情况。同时, 体外扩增的骨髓间充质干细胞（MSC） 与正常供体小鼠的造血干细胞 （HSC） 进行二维共培养 （2D CFU-GM）, 通过 2D CFU-GM 检测辐射损伤后药物作用的 MSC 促进 HSC 的增殖能力。结果 与照射对照组相比, 3 个剂量组的 CFU-GM 数目显著增多, 中剂量组及高剂量组 CFU-S、 CFU-F、 2D CFU-GM 增殖能力显著提高 （均 P＜0.05）。结论 抗衰片可以促进电离辐射损伤后小鼠造血系统重建。     

Biochemical,histopathological, and transmission electron microscopic ultrastructural changes in mice after exposure to silver nanoparticles

Four‐week‐old mice, weighing about 25–35 g were divided into five groups (8 mice in each group): vehicle control, low‐ (0.5 g/kg), middle‐ (1 g/kg), high‐ (3 g/kg), and exceptionally high‐dose (5 g/kg). After first and second weeks of intraperitoneal exposure to AgNPs, biochemical, histopathological, and electron microscopic ultrastructural changes were investigated. No significant changes were observed in SGOT and ALP levels after first week of exposure, while the level of SGPT significantly increased (p < 0.05) in 2nd week treated mice, indicating that inflammatory of liver might be induced by high‐dose (3 and 5 g/kg) of AgNPs. No obvious changes were observed for UA and BUN in all groups of treated mice. However, significant (p < 0.05) decrease in CR level was noticed in all groups of treated mice only at high‐dose (3 and 5 g/kg). No remarkable changes in lipid profile were observed. Light microscopic histopathological investigation shows that first week treatment had not perceptible effect on the cytoarchitecture on liver, kidney, and spleen; while, second week treatment had only sporadic mild effects on these organs. However, no ultrastructural electron microscopic changes were observed in liver, kidney, and spleen of mice treated with 0.5, 1, and 3 g/kg of AgNPs when sacrificed on first and second week; while, exceptionally high‐dose (5 g/kg) of AgNPs resulted in slight nuclear chromatin condensation and irregularities in nuclear membrane. The results suggested that AgNPs could be well tolerated in mice when given intraperitoneally and no death has been found during the experiment in any groups of treated mice. Interestingly, significant (<0.05) decrease in glucose levels in all experiment group is suggestive of curious hypoglycemic role of AgNPs warranting further study to explore its possible therapeutic potential in hyperglycemic conditions as well as its mechanism of action at molecular level. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 945–956, 2016.     

双黄连片对小鼠流感病毒和腺病毒感染的保护作用

目的观察双黄连片在实验动物体内抗流感病毒和腺病毒的作用,为临床用药提供试验依据。方法建立流感病毒鼠肺适应株FM1感染小鼠模型和腺病毒ADV3株感染小鼠模型,分别灌胃给予高、中、低剂量双黄连片,设立病毒唑对照和正常对照组,观察各组小鼠的死亡数、测定小鼠存活时间、肺指数和肺组织流感病毒滴度。结果双黄连片可明显降低流感病毒和腺病毒感染小鼠的死亡率,延长肺炎小鼠的存活时间,降低肺炎小鼠的肺指数;同时,双黄连片还能降低肺组织中流感病毒的滴度。结论双黄连片在小鼠体内有明显抑制流感病毒和腺病毒的作用。     

1-Naphthol--single and repeated dose (30-day) oral toxicity studies in the mouse

The oral toxicity of 1-naphthol in Charles River CD1 mice was investigated in single (2, 1 and 0.5 g/kg body weight) and 30-day repeat dosing (200, 100 and 50 mg/kg body weight) studies. In the single-dose study, animals dosed by oral gavage at 2 g/kg body weight either died or were killed in extremis between 15 and 90 min after dosing, and although the animals treated at 1 g/kg body weight survived to the end of the study (14 days post-dosing), one male in the 0.5 g/kg body weight dose group was killed in extremis approximately 2 hr after treatment. Acute dosing was associated with histopathological lesions seen in the kidneys and stomachs of mice from all treatment groups. The kidney lesions consisted of degeneration of the distal tubule epithelium, papillary necrosis and tubular dilatation. Gastric changes characterized by splitting of the epithelium of the forestomach and sloughing of the superficial epithelium of the glandular mucosa were generally accompanied by vascular congestion and acute inflammatory cell infiltration. In the 30-day study, mice dosed by oral gavage at 50 and 100 mg/kg body weight tolerated the treatment well, as did the female mice treated at 200 mg/kg body weight. Three male mice in the 200 mg/kg body weight group did, however, show gastric histopathological effects. Two of the mice (one killed in extremis on the fourth day of the study with the other surviving treatment) showed focal mucosal erosion, and a third (killed in extremis on the twentieth day of the study) exhibited peeling of the mucosa of the forestomach. Both of these gastric lesions were considered to be related to treatment at 200 mg/kg body weight. None of the mice in the 30-day study showed any kidney lesions or changes in haematology or clinical chemistry parameters.     

Effects of TJ-41 (Tsumura Hochu-ekki-to) on spermatogenic disorders in mice under current treatment with adriamycin

Experiments were performed to investigate the effects of TJ-41 on spermatogenic disorders under current treatment with adriamycin (ADR). Male ICR mice were intraperitoneally injected with ADR at the dose of 0.15 mg/kg, twice a week for 5 weeks. Simultaneously, these mice were orally administered TJ-41 at the dose of 1, 2 or 4 g/kg for 12 weeks. The effects of TJ-41 were evaluated by histological analysis of germ cells in the testis at 7 weeks after the last injection of ADR. TJ-41 at a dose of 4 g/kg significantly inhibited the decrease of testis weight in mice treated with ADR. TJ-41 at doses of 1 and 4 g/kg significantly decreased the proportion of seminiferous tubules without germ cells as compared with the ADR-treated group. On the other hand, TJ-41 at doses of 1 and 4 g/kg significantly increased the proportion of normal seminiferous tubules and the Sertoli cell ratio of spermatocytes as compared with the ADR-treated group. These results indicate that TJ-41 may qualitatively and quantitatively protect against the decrease of germ cells in the testis of mice treated with ADR.     

Histopathologic changes in the uterus, cervix and vagina of immature CD-1 mice exposed to low doses of perfluorooctanoic acid (PFOA) in a uterotrophic assay

The estrogenic and antiestrogenic potential of perfluorooctanoic acid (PFOA) was assessed using an immature mouse uterotrophic assay and by histologic evaluation of the uterus, cervix and vagina following treatment. Female offspring of CD-1 dams were weaned at 18days old and assigned to groups of equal weight, and received 0, 0.01, 0.1, or 1mg PFOA/kg BW/d by gavage with or without 17-β estradiol (E(2), 500μg/kg/d) from PND 18-20 (n=8/treatment/block). At 24h after the third dose (PND 21), uteri were removed and weighed. Absolute and relative uterine weights were significantly increased in the 0.01mg/kg PFOA only group. Characteristic estrogenic changes were present in all E(2)-treated mice; however, they were minimally visible in the 0.01 PFOA only mice. These data suggest that at a low dose PFOA produces minimal histopathologic changes in the reproductive tract of immature female mice, and does not antagonize the histopathologic effects of E(2).     

二苯乙烯苷对D-半乳糖致脑老化小鼠学习记忆及神经营养因子的影响

目的 :观察何首乌提取物二苯乙烯苷 (TSG)对D -半乳糖致痴呆模型小鼠学习记忆及脑内神经营养因子表达的影响。方法 :将小鼠随机分为正常对照组、D -半乳糖模型组、VitE阳性对照组及TSG低、中、高剂量 (0 033、0 1、0 3g/kg)6个组 ,除正常对照组外 ,其余各组小鼠在建立脑老化模型的同时灌胃给予相应药物60d ,随后进行Morris水迷宫测试 ,并采用免疫组化的方法检测TSG对神经生长因子 (NGF)和神经营养因子 -3(NT -3)的影响。结果 :与正常对照组比较 ,模型组小鼠在Morris水迷宫测试中游出时间和游出距离延长 ,海马CA1区NGF和NT -3的表达明显减少 ;TSG则能缩短小鼠游出时间和游出距离 ,增加海马CA1区NGF和NT -3的表达。结论 :TSG能明显提高学习记忆能力 ,对阿尔茨海默病可能具有防治作用。     

乙酰唑胺对缺氧耐受小鼠血清T-chE和T-AOC的影响

目的：研究乙酰唑胺对小鼠缺氧耐受的影响和机制。方法：小鼠随机分四组：生理盐水对照组、心得安对照组、乙酰唑胺高剂量组和乙酰唑胺低剂量组。高剂量组予以乙酰唑胺1g/kg、低剂量组予以乙酰唑胺0．2g／kg灌胃，阳性对照组给予心得安0．16g/kg灌胃，正常对照组用20g/kg生理盐水灌胃，各组小鼠均每天灌胃一次，连续5天并于末次给药1小时后测定小鼠在室温空调25℃条件下的常压缺氧耐受能力；同时在小鼠死亡时尽快断头取血，以3000r／min，离心5分钟，按试剂盒说明书测定血清胆碱酯酶（T-ChE）活性和总抗氧化能力（T-AOC）。结果：乙酰唑胺低剂量组和高剂量组小鼠耗氧率均较生理盐水组显著降低（均P〈0．01），与心得安组比较差异有显著性（分别P〈0．01和P〈0．05）；乙酰唑胺高剂量组T-ChE活性和T—AOC均明显比生理盐水组高（均P〈0．01），比心得安组显著增高（分别P〈0．01和P〈0．05）。结论：乙酰唑胺高、低剂量均能提高小鼠抗常压的缺氧耐受能力，与提高T-AOC和T-ChE活性有关。     

大剂量重组人粒细胞集落刺激因子对8.0Gy ^60Co γ射线照射小鼠长期存活率及远后效应的影响

目的探索重组人粒细胞集落刺激因子（rhG-CSF）对8.0Gy60Coγ射线照射小鼠长期存活率及远后效应的影响。方法 70只雄性C57BL/6小鼠,随机分为正常对照、照射对照及rhG-CSF大、中、小剂量治疗共5组,除正常对照组外,其他4组均接受8.0Gy60Coγ射线照射。治疗组小鼠于照射后0.5和24h两次分别皮下注射rhG-CSF1000、500和250μg/kg,随时记录各组动物存活率,照射后70、160和300d进行外周血细胞计数分析,300d时检测各组存活小鼠造血和免疫相关指标。结果照射对照组动物照后19d内全部死亡,平均存活时间（12.1±3.0）d;rhG-CSF1000μg/kg治疗组照射后30、100和300d存活率分别为86.7%、86.7%和80.0%,死亡小鼠平均存活时间较照射对照组明显延长（P〈0.01）。照后300d时,rhG-CSF1000μg/kg治疗组的外周血红细胞和血小板计数均与正常对照组没有统计学差异,骨髓混合细胞集落形成单位数量显著低于正常对照组（P〈0.01）;rhG-CSF治疗组的CD4＋/CD8＋比值倒置且250μg/kg剂量组明显低于正常对照组（P〈0.05）;rhG-CSF治疗组造血和免疫器官的组织病理切片结果显示仍然存在不同程度的病变。结论 rhG-CSF1000μg/kg治疗可以显著提高8.0Gy60Coγ射线照射小鼠存活率,但照射后300d造血和免疫系统相关指标尚未完全恢复正常。     

Investigation of a possible sensitization development to a challenge dose of ethanol after 2 weeks following the single injection in mice

In the present study, a possible sensitization development to a single injection of ethanol in mice was investigated. Subjects were adult male Swiss-Webster mice. Ethanol (0.5-4 g/kg) or saline (control) was intraperitoneally injected to mice. Horizontal, vertical and ambulatory locomotor activities were recorded for 30 min immediately following the ethanol or saline injections. After 2 weeks, each group of mice was randomly assigned to two groups. A single challenge dose of ethanol (1 g/kg) was administered to the first group, and saline was injected to the second group. Then, the locomotor activities were recorded for 30 min. In the first experiment, ethanol significantly increased the horizontal and ambulatory activities of the mice at the doses of 0.5 and 1 g/kg, but not at 2 g/kg, while they were decreased at the dose of 4 g/kg. Ethanol (0.5 g/kg) also significantly increased the vertical activity. After 2 weeks, the challenge injection of ethanol (1 g/kg) produced some significant increases in the horizontal and ambulatory activities of the group pretreated with ethanol (2 g/kg). It did not cause any significant change on the locomotor activities of the other three groups treated with lower (stimulant) or higher (depressant) doses of ethanol. In addition, there was no significant difference between locomotor activities of the groups challenged with saline. However, a two-way ANOVA of the data on the challenge injections did not indicate any sensitization development to the effects of ethanol on locomotor activities of the mice. Our results suggest that a locomotor sensitization did not develop to a single injection of ethanol after 2 weeks following the first injection in mice.