抗生素89—07围产期毒性试验

ＳＤ大鼠怀孕的第１５天开始直至产后第２８天连续皮下给予抗生素８９－０７１００、２００和４００ｍｇ／（ｋｇｄ）。结果４００ｍｇ／（ｋｇｄ）组有１只母鼠于产后第７天死亡，但对妊娠期及泌乳期母鼠的平均体重增长无影响（Ｐ＞０．０５），对母鼠的妊娠期、产仔数、活仔数也无影响（Ｐ＞０．０５），同样剂量下Ｆ１代仔鼠断乳后的平均体重增长（Ｐ＞０．０５），Ｆ１代的发育指标、反射发育、感觉运动协调以及生殖功能均无影响（Ｐ＞０．０５），因此抗生素９８－０７是不具有围产期毒性的药物。     

健脾生血颗粒对围产期大鼠的毒性研究

目的:考察健脾生血颗粒对围产期大鼠的毒性作用。方法:将受孕大鼠按体质量随机分为阴性对照组和健脾生血颗粒低、中、高剂量组(0.77、2.31、6.93 g/kg),每组21只,从妊娠第15天开始至分娩后第21天止每天ig相应药物1次。观察健脾生血颗粒对母代大鼠一般毒性和生育能力的影响,对F1代仔鼠运动能力、学习记忆能力、生育能力以及对F2代仔鼠早期发育能力的影响。结果:对母代的毒性作用方面,健脾生血颗粒高剂量组母代大鼠妊娠天数较阴性对照组显著延长(P<0.05),给药初期体质量显著降低(P<0.01)。对子代的毒性作用方面,健脾生血颗粒高剂量组F1代仔鼠初生体质量较阴性对照组显著降低(P<0.05),第4、5次发现水下平台时间较阴性对照组显著缩短(P<0.01);对F1代仔鼠生育能力及F2代仔鼠早期发育能力均未见明显影响(P>0.05)。健脾生血颗粒中、低剂量组子代大鼠各指标均未见受到明显影响。结论:健脾生血颗粒对母代及子代大鼠均未见毒性反应的剂量为2.31 g/kg。     

左旋千金藤立定对溴隐亭诱导的哺乳期大鼠促乳素水平低下的拮抗作用

目的:研究左旋千金藤立定(SPD)对溴隐亭(Bro)诱导的促乳素(PRL)水平低下的对抗作用。方法:哺乳期母鼠sc Bro 0.5mg·kg~(-1)·d~(-1),PRL显著降低,乳腺组织发育不良,而且仔鼠体重增长缓慢。用放免法测定母鼠PRL,检查乳腺发育状况,评价SPD的对抗作用。结果:SPD30及100mg·kg~(-1)·d~(-1)ip,能够显著对抗Bro诱导的母鼠PRL降低,分娩后d15PRL为11±4及23±6μg·L~(-1)(生理盐水为7±2),而且乳腺组织发育正常,仔鼠在出生后d11—15内迅速生长发育。结论:SPD能阻断大鼠脑垂体前叶的D_2受体,是一个D_2受体的拮抗剂。     

注射用甲磺酸胺银杏内酯B对围产期仔鼠生长及组织器官发育的影响

目的 观察注射用甲磺酸胺银杏内酯B(XQ-1H)对哺乳期仔鼠的一般生长状况以及对仔鼠组织器官发育的影响,研究其伴随的毒代动力学,为XQ-1H围产期安全性评价提供依据.方法 将108只受精SD大鼠随机均分为溶媒对照组和3个给药(20、10、5 mg·mL-1)实验组.对照组大鼠给予0.9％氯化钠溶液,实验组给药剂量分别为100、50、25 mg·kg-1 ·d-1.于妊娠期第15天开始给药,每天1次,连续给药至哺乳期结束(出生后第21天),于尾静脉注射,给药容积为5 mL·kg-1.实验组取3只孕鼠于妊娠20 d进行剖宫,取各给药组仔鼠进行解剖,检查XQ-1H是否可通过胎盘屏障进入仔鼠.仔鼠出生4d后,每窝留10只,各给药组选择2只剔除仔鼠进行解剖,检查XQ-1H是否可通过乳汁分泌进入仔鼠.给药组24只孕鼠于哺乳期结束时处死母鼠,观察指标包括仔鼠的一般观察、出生畸形、体重、摄食量及解剖后观察组织器官的发育情况.结果 XQ-1H可通过母体胎盘屏障,不可由哺乳通过乳汁传递给子代;与对照组相比,各给药组仔鼠一般生长状况未出现统计学差异;子代各组织器官发育良好,与对照组比较无统计学差异.结论 XQ-1H对子代生长及组织器官发育无不良影响.     

盐酸苯环壬酯对小鼠的围产期毒性试验研究

盐酸苯环壬酯分成２．５、１２．５和６２．５ｐｐｍ３个浓度组，溶于自一不中，供孕鼠从妊娠ｄ１５开始至断乳时饮用。结果显示，在相当于人临床用量１５－７５倍剂量范围内，该药对小鼠胚胎后期生长发育、母鼠分娩、哺乳及新生小鼠神经行为发育无明显影响。６２．５ｐｐｍ组孕鼠给药期间体重增长抑制，死产仔鼠数增多，雄仔鼠肝脏重量增加，表现出一定的母体毒性和发育毒性。     

丙戊酸诱导的SD大鼠和C57小鼠孤独症谱系障碍模型的比较

目的比较丙戊酸(VPA)诱导的C57小鼠和SD大鼠孤独症谱系障碍(ASD)模型在生理发育、神经发育和孤独症样行为等方面的异同,为合理选择ASD动物模型提供实验依据。方法孕12.5 d的C57小鼠和SD大鼠,分别ip给予VPA 600 mg·kg~(-1)或无菌生理盐水(正常对照组)。观察各组孕鼠出产率;新生仔鼠的外观畸形率;雄性仔鼠的4日存活率、体质量、尾长和尾部外观畸形率,以及腹毛生长、门齿萌出和睁眼时间等生理发育指标;雄性仔鼠的平面翻正反射、空中翻正反射、转体、断崖回避反射、直线爬行、抓杆和听觉惊愕反射行为达到阳性的天数等神经发育指标;并通过旷场实验、三箱社交实验和自我捋毛实验检测各组雄性仔鼠的孤独症样行为。结果与各自正常对照组相比,C57小鼠VPA组孕鼠出产率明显降低(P<0.05),新生仔鼠外观畸形率显著升高(P<0.01),而SD大鼠VPA组孕鼠出产率和新生仔鼠外观畸形率均无差异。C57小鼠VPA组雄性仔鼠较其正常对照组的4 d存活率降低(P<0.05)、在出生后20和25 d时体质量较轻(P<0.05)、门齿萌出和睁眼时间延迟(P<0.05,P<0.01);SD大鼠VPA组雄性仔鼠在相同日龄时体质量虽也明显低于其正常对照组(P<0.01),但4 d存活率、腹毛生长、门齿萌出时间和睁眼时间无差异。C57小鼠VPA组雄性仔鼠的转体和抓杆实验达阳性天数明显滞后(P<0.05),但在平面翻正、断崖回避、空中翻正、直线爬行和抓杆实验中无明显差异;SD大鼠VPA组雄性仔鼠的平面翻正(P<0.01)、断崖回避(P<0.01)、空中翻正(P<0.05)、直线爬行(P<0.01)和抓杆实验(P<0.01)达阳性天数均有显著延迟,但在转体实验中无明显差异。在三箱社交实验、旷场实验和自我捋毛实验中,C57小鼠VPA组雄性仔鼠空间探索力和对新鲜事物偏好降低(P<0.05);SD大鼠VPA组雄性仔鼠不仅出现明显的空间探索力下降(P<0.01),还伴有明显的社交缺陷(P<0.01)、缺乏社交偏好和新鲜事物偏好(P<0.01)和重复刻板行为(P<0.05)。结论孕中期注射VPA的C57小鼠和SD大鼠,其子代雄性仔鼠均可出现典型的孤独症谱系障碍核心症状,但在母鼠孕产情况、建模成本和模型表观效度等方面,SD大鼠较C57小鼠更适于制备ASD动物模型。     

妊娠中期可卡因对小鼠的发育毒性

目的:探讨可卡因对小鼠妊娠中期的发育毒性,尤其是对脑发育的影响.方法:建立妊娠中期给药的小鼠动物模型,体重相近的妊娠母鼠被分为三组:(1)可卡因注射自由饮食组(COC);(2)盐水注射伴有饮食对照组(SPF),饮食参考体重相近、妊娠时间相同的COC组母鼠;(3)盐水注射自由饮食组(SAL).从妊娠第8天(E8)至第12天(E12)给药,记录母鼠、胎鼠和仔鼠的各项生理指标,并用HPLC分析各组胎鼠纹状体中多巴胺、5-HT含量的变化.结果:尽管COC和 SPF组母鼠与 SAL组母鼠相比摄食量少,体重增加量少,但E17 天取材时,仅COC组胎鼠表现为脑和纹状体重量低;COC组仔鼠生后第 1天(P1)双顶径(BPD)也小于其它两组仔鼠.此外,COC组胎鼠表现出脑/体重比的降低,说明宫内暴露可卡因引起的胎鼠的发育迟缓是一个不平衡过程,脑组织的受累比其它组织严重.神经递质分析和组织学分析表明 COC组胎鼠脑内多巴胺和5-羟色胺的水平增高,肝脏呈现出形态学改变.结论:妊娠中期暴露可卡因可引起胎鼠宫内发育迟缓,尤其是脑发育迟缓.单纯母体营养不良在宫内暴露可卡因引起的后代发育迟缓过程中不能起决定性作用,而可能是药物直接作用的结果.     

甲基汞对大鼠的行为致畸效应研究

目的探讨妊娠期甲基汞暴露对Wistar大鼠的母体毒性及仔代的行为致畸效应.方法 Wistar孕鼠80只于妊娠第6～9天采用甲基汞0.00、0.01、0.05和2.00mg·kg-1@d-1连续灌胃染毒.分别进行母体毒性、胚胎毒性、仔鼠早期生理发育和神经行为发育指标、仔鼠迷宫和程序控制行为测试、亲仔两代大鼠脑组织形态学观察和单胺类神经递质(去甲肾上腺素、多巴胺、5-羟色胺)的测定.整个实验采用双盲法.结果未观察到明显的母体毒性;3个剂量组胎仔的体重、尾长均低于对照组(P＜0.01);各剂量组仔鼠的体重增长、早期生理及神经行为发育滞后于对照组(P＜0.05);各剂量组仔鼠迷宫错误次数均比对照组多(P＜0.05),具有剂量-效应关系(rs=0.257,P＜0.05);程序控制行为学习成绩比对照组降低(P＜0.05),有剂量-效应关系(rs=-0.727 3,P＜0.01);各剂量组母鼠和仔鼠脑组织均未见形态学改变,但脑组织单胺类神经递质含量均比对照组明显增高(P＜0.05),有剂量-效应关系(s=0.712 4～0.925 7,P＜0.01).结论甲基汞在不引起可观察到母体毒性剂量下,就可产生胚胎毒性,影响仔鼠神经系统的发育,导致神经行为功能的改变.     

环磷酰胺、维生素A和珊瑚提取液发育毒性体内筛选试验

Chernoff/Kavlock试验是近年来发展的发育毒性体内筛选试验。本文利用此试验筛选和预测环磷酰胺(CP)、维生素A(VA)及珊瑚提取液的发育毒性。昆明种小鼠,于孕第6～14日隔日一次染毒。CP10mg/kg/次腹腔注射和VA45mg/kg/次灌胃可引起母鼠体重增长降低、仔鼠出生第1日     

出生前后双酚A暴露对小鼠不同时期血清白介素-17白介素-23的影响

目的研究出生前后高剂量双酚A(BPA)暴露对小鼠不同时期血清白介素-17(IL-17)和白介素-23(IL-23)水平的影响,初步探讨BPA发育免疫毒性机制。方法将确认妊娠的ICR母鼠随机分为空白对照组、溶剂对照组、BPA剂量组(高、中、低组分别为2.0、0.5和0.125 g/L BPA);母鼠自妊娠第0 d(GD0)至仔鼠断乳(出生后第21 d,PND21)经饮水暴露于BPA。分别于PND7、PND21和PND42取仔鼠外周血用ELISA检测IL-17和IL-23含量。结果在PND7和PND21时,随母鼠BPA暴露剂量的增加,仔鼠血清IL-17和IL-23含量逐渐上升,2.0 g/L BPA组与空白对照组和溶剂对照组相比,差异均有统计学意义(P值均<0.05)。在PND42时,各BPA暴露组仔鼠血清IL-17和IL-23含量与空白对照组和溶剂对照组差异均无统计学意义(P值均>0.05)。结论出生前后BPA暴露可能引起子代断乳前体内Th17细胞分泌的细胞因子含量升高。     

革皮氏海参总皂苷的安全性评价研究

目的对革皮氏海参总皂苷的使用安全性进行评价,阐明其毒性及潜在的危险。方法将健康ICR小鼠随机分为正常组和革皮氏海参总皂苷不同剂量组,每组5只。根据预实验的结果灌胃剂量分别为0.464、1、2.15和4.64 g.kg-1bw,一次性灌胃后连续观察14 d,记录各组的死亡数;另取健康ICR小鼠50只,随机分为正常对照组、阳性对照组和革皮氏海参总皂苷低、中、高剂量组,每组10只,♀♂各半,取股骨骨髓细胞涂片观察骨髓嗜多染红细胞微核率的变化;大鼠30 d喂养实验中,将Wistar大鼠随机分为4组,每组♀♂各10只,给大鼠灌胃不同浓度(分别为20、50和100mg.kg-1)的革皮氏海参总皂苷30 d后,进行体重、外周血象、血糖、血脂、肝脏功能、心肌损伤、肾脏功能等指标检测,取肝、肾、睾丸、卵巢、胃、心、肺进行了组织病理学观察。结果革皮氏海参总皂苷对♂小鼠的LD50为1.08 g.kg-1,♀小鼠LD50为1.10 g.kg-1,属低毒级;骨髓细胞微核实验结果为阴性;30 d喂养实验中,不同剂量组大鼠各项检测指标与正常组相比较差异均无显著性(P>0.05),组织病理观察发现革皮氏海参总皂苷对大鼠睾丸有轻微毒性作用。结论革皮氏海参总皂苷的急性毒性级别为低毒,未发现遗传毒性,存在一定的亚急性毒性。     

海洋真菌多糖YCP对小鼠扶正减毒作用的研究

从海洋真菌YC中提取的真菌多糖YCP,选择9,3,1 mg/kg的不同剂量,分别联合60Co放疗和Cy化疗正常小鼠和Heps荷瘤鼠,观察药物对放、化疗的减毒作用。以荷瘤小鼠观察药物对小鼠的扶正作用。结果:YCP(9,3,1 mg/kg)剂量组可显著地对抗由大剂量Cy造成的正常小鼠外周血白细胞,骨髓有核细胞数和胸腺指数的下降(P<0.01,P<0.05)。YCP(9,3 mg/kg)剂量组可显著地抑制由大剂量Cy和60Co照射造成的Heps荷瘤小鼠外周血白细胞,骨髓有核细胞数和脾脏指数和胸腺指数的下降(P<0.01,P<0.05)。YCP(9,3 mg/kg)可显著提高S180荷瘤小鼠的吞噬指数k和血清半数溶血值(P<0.01,P<0.05)。结论YCP可明显对抗由60Co照射,大剂量化疗药Cy引起的正常和荷瘤小鼠的血液和骨髓抑制毒性。YCP可显著提高S180荷瘤小鼠免疫功能。     

Acute, subacute toxicity and genotoxic effect of Bio-Quinone Q10 in mice and rats

In the present study, the acute, subacute and genetic toxicity of Coenzyme Q10 (CoQ10) in the form of Bio-Quinone (Pharma Nord, Denmark) was assessed. LD(50) of CoQ10 by oral treatment was greater than 20g/kg body weight in both female and male mice. Genotoxicity was assessed in mice by Ames test in Salmonella typhimurium strains TA97, TA98, TA100 and TA102, by bone marrow micronucleus test and sperm abnormality. Thirty-day subacute toxicity was conducted with oral daily dose at 0, 0.56, 1.13 and 2.25g/kg body weight in rats. No significant changes in body weight, food intake, behavior, mortality, hematology, blood biochemistry, vital organ weight, sperm abnormality, mutagenicity and micronucleus formation were observed and no clinical signs or adverse effects were detected by administration of CoQ10. These results support the safety of CoQ10 for oral consumption.     

Four-week inhalation toxicity, mutagenicity and immunotoxicity studies of Keum-Yeon-Cho (NosmoQ), tobacco substitute composition, in mice

Safety of Keum-Yeon-Cho (NosmoQ), a tobacco substitute composition, was evaluated in terms of acute- and 4 weeks repeated-inhalation toxicity, mutagenicity, and immunotoxicity using Balb/c mice. The air inside the inhalation chamber was collected and analyzed by GC-MS. In acute inhalation toxicity test, male and female mice were exposed to 40 Keum-Yeon-Cho cigarettes. The 50% lethal concentration (LC(50)) of NosmoQ was considered to be much higher than 40 cigarettes in both sexes. In 4-week repeated inhalation toxicity test, male and female mice were exposed for 6 h/day, 5 days/week for 4 weeks to 10 and 20 cigarettes per day, while control mice were exposed to filtered air. Our data indicated that no observed adverse effect level (NOAEL) of Keum-Yeon-Cho should be over 20 cigarettes per day. Results of Salmonella typhimurium reversion assay with/without histidine moiety, in vivo chromosomal aberration and in vivo micronucleus assays using mouse bone marrow cells revealed that Keum-Yeon-Cho has no mutagenicity. Evaluation of peripheral cellular immunity of mice treated with Keum-Yeon-Cho using in vitro lymphocyte proliferation assay showed no significant difference in mean stimulation index (SI) between mice exposed to Keum-Yeon-Cho and control mice. Mean CO concentrations and total particulate matter contents of 10 and 20 cigarettes were 21.1±1.23 and 40.7±1.21 ppm (mean±S.D., n=5), and 25.7±3.09 and 59.0±4.0 mg dry weight (mean±S.D., n=5), respectively. Although at negligible concentration (less than ppb level) several polycyclic aromatic hydrocarbons (PAHs) were also detected, these results indicate that NosmoQ has no toxic effect on mice.     

An assessment of chloramphenicol and thiamphenicol in the induction of aplastic anaemia in the BALB/c mouse.

The potential of the antibiotics chloramphenicol succinate (CAPS) and thiamphenicol (TAP) to induce aplastic anaemia in the female BALB/c mouse was investigated. CAPS was administered at 2000 mg/kg, and TAP at 850 mg/kg, daily by gavage, for 17 days. At 1, 13, 22, 41, 98 and 179 days after the final dose of each antibiotic, mice (n = 4 or 5) were sampled for haematological examination and haematopoietic stem cell assays. Both CAPS and TAP induced significant reductions in red blood cell count, haematocrit and haemoglobin values at day 1 post dosing; counts of colony-forming units-erythroid and colony-forming units-granulocyte-macrophage, were similarly significantly decreased at this time. All these reduced parameters returned towards normal at days 13 and 22. At days 41, 98 and 179, results for all haematological values and stem cell assays in both CAPS- and TAP-treated mice compared with the controls; there was no evidence of a reduction in peripheral blood values or bone marrow parameters at the later sampling points, as would be expected in a developing or overt bone marrow aplasia. We therefore consider that the administration of CAPS and TAP, which have been associated with the development of aplastic anaemia in man, induce a reversible anaemia, but not a chronic bone marrow aplasia, when given at haemotoxic dose levels for 17 days in the BALB/c mouse.     

灵芝冲剂对大鼠的长期毒性实验研究

目的观察连续灌胃灵芝冲剂对大鼠产生的毒性反应。方法灵芝冲剂1.5 g.kg-1、3.0 g.kg-1、6.0 g.kg-1连续灌胃26周,给药结束时测试大鼠体重、尿液、血液学常规、血液生化、脏器系数及病理组织学变化。结果各剂量组大鼠发育正常,各项检测结果未见与用药相关的异常变化,主要脏器病理组织学检查未见毒性病变。结论灵芝冲剂给予大鼠长期连续灌胃未见明显毒性反应,长期服用安全。     

参麦注射液对小鼠血常规的影响及其脏器保护作用

目的:观察参麦注射液对正常和顺铂化疗小鼠血常规、脏器系数、脏器组织形态学的影响,初步探讨其安全性和化疗辅助疗效。方法:健康小鼠,分为空白对照组、生理盐水对照组(0.125 mL/10 g体重)、参麦注射液组(0.125 mL/10 g体重)、顺铂组(3.5 mg.kg-1体重)、参麦注射液+顺铂组,腹腔注射给予药物7 d后,取血处死,测定血常规;取内脏,肉眼观察,计算脏器系数并切片,做HE染色,观察内脏的受损程度。结果:与生理盐水组相比,参麦注射液组白细胞数显著提高(P<0.01),红细胞和血小板数量有增加趋势,脾脏指数显著上升,心、肝、肺、肾脏器系数无显著变化,各脏器均未见病变;与顺铂组相比,参麦注射液+顺铂组小鼠的肝脏脂肪性病变和坏死得到改善,肾小管上皮细胞水变性明显减轻。结论:研究结果显示参麦注射液能促进正常小鼠的骨髓造血功能,未对小鼠脏器造成毒性损害;并对顺铂所致的小鼠肾、肝损伤有一定保护作用。     

Male mice deficient in microsomal epoxide hydrolase are not susceptible to benzene-induced toxicity.

Enzymes involved in benzene metabolism are likely genetic determinants of benzene-induced toxicity. Polymorphisms in human microsomal epoxide hydrolase (mEH) are associated with an increased risk of developing leukemia, specifically those associated with benzene. This study was designed to investigate the importance of mEH in benzene-induced toxicity. Male and female mEH-deficient (mEH-/-) mice and background mice (129/Sv) were exposed to inhaled benzene (0, 10, 50, or 100 ppm) 5 days/week, 6 h/day, for a two-week duration. Total white blood cell counts and bone marrow cell counts were used to assess hematotoxicity and myelotoxicity. Micronucleated peripheral blood cells were counted to assess genotoxicity, and the p21 mRNA level in bone marrow cells was used as a determinant of the p53-regulated DNA damage response. Male mEH-/- mice did not have any significant hematotoxicity or myelotoxicity at the highest benzene exposure compared to the male 129/Sv mice. Significant hematotoxicity or myelotoxicity did not occur in the female mEH-/- or 129/Sv mice. Male mEH-/- mice were also unresponsive to benzene-induced genotoxicity compared to a significant induction in the male 129/Sv mice. The female mEH-/- and 129/Sv mice were virtually unresponsive to benzene-induced genotoxicity. While p21 mRNA expression was highly induced in male 129/Sv mice after exposure to 100-ppm benzene, no significant alteration was observed in male mEH-/- mice. Likewise, p21 mRNA expression in female mEH-/- mice was not significantly induced upon benzene exposure whereas a significant induction was observed in female 129/Sv mice. Thus mEH appears to be critical in benzene-induced toxicity in male, but not female, mice.     

间充质干细胞的毒性作用研究

目的 研究间充质干细胞对小鼠的急性毒性作用, 初步探讨其毒性反应, 为间充质干细胞在临床上安全使用提供指导。方法 选用ICR小鼠, 根据预试结果, 实验分为3组:对照组和间充质干细胞高、低剂量组, 每组分别采用20只实验动物, 雌雄各半, 分别观察小鼠对间充质干细胞的反应。结果 实验期间, 各给药组小鼠各检查时间点平均体质量与对照组比较均无明显差异, 且小鼠被毛光泽, 精神状态和自主活动均正常, 分泌物和排泄物等均未见明显异常。表明间充质干细胞制剂静脉给药对小鼠体质量增长无明显影响。与对照组比较, 间充质干细胞低、高剂量组雄性小鼠脾、肺质量及系数明显升高, 高剂量组雌性大鼠肺脏系数明显升高。结论 间充质干细胞制剂无明显的毒副作用, 且在肺脏和脾脏等部位滞留。     

因宁片的急性和慢性毒性实验研究

目的:研究因宁片的急性和慢性毒性作用,评价其安全性。方法:40只昆明种小鼠随机分为空白对照(等容生理盐水)和因宁片(32g.kg-1)组。因宁片组24h内连续2次(间隔6h)灌胃给药后观察小鼠的一般状况、死亡情况、记录体重和摄食量,14d后处死并作大体解剖,肉眼观察各脏器变化,计算最大耐受量(MTD)。48只SD大鼠随机分为空白对照(等容生理盐水)与因宁片高、中、低剂量(6.0、3.0、0.6g.kg-1)组。灌胃给药,每天1次,连续30d,末次给药24h后处死大鼠,腹主动脉取血测定各项血液学指标和血液生化指标,记录各脏器重量、体重、摄食量,计算脏器系数,并作病理切片,观察组织形态学的变化。结果:急性毒性实验中因宁片组各项指标正常,MTD为32g.kg-1;慢性毒性实验中因宁片高、中、低剂量组大鼠一般状况正常,各组中未见多指标同时明显异常,组织结构未见明显异常。结论:因宁片毒性低,可为临床安全用药提供理论依据。