中药毒性相关数据库的研究现状及对比研究

中药毒性研究是中药安全性研究的重要议题,将具有毒性的中药成分及其作用机制进行整理是进行中药毒性研究的基础。因此,通过当前国内外中药毒性研究相关的数据库进行综述,总结中药毒性研究相关数据库的研究现状,突出中药毒性研究相关数据库在科学研究中的重要性,为中药毒性研究工作提供参考,促进中药毒性研究的进一步发展。     

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,称量肝脏、肾脏湿重并计算脏器系数,采用苏木素-伊红(HE)染色检测其组织形态学改变,并检测大鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、尿素氮(BUN)和肌酐(CRE)的含量。结果黄芩苷200 mg/kg组大鼠给药56 d后体质量、肾脏系数均低于对照组(P<0.05),组织形态学显示肾小球萎缩变小、肾小管明显萎缩且上皮细胞发生坏死,肝脏未见明显异常。黄芩苷200 mg/kg组大鼠给药56 d后,血清中BUN、CRE含量高于对照组,差异均有统计学意义(P<0.05);黄芩苷100 mg/kg组各时间点和黄芩苷200 mg/kg组给药28 d后各指标均未见明显异常。结论在本试验条件下,黄芩苷给药对雄性大鼠有一定的肾脏毒性作用。     

亚稀褶红菇对大鼠致死毒性分级研究

目的 为了解亚稀褶红菇对大鼠的半数致死量（LD50）,进行毒性分级。方法 采用急性毒性试验经典方法寇氏法,设亚稀褶红菇175、248、350、495、700 mg/kgBW共 5个剂量组和阴性对照组(等体积生理盐水),每组大鼠12只,雌雄各半,腹腔注射,连续观察14 d大鼠的毒性反应和死亡情况。并对试验大鼠进行病理组织学检查。结果 根据试验结果,经计算,亚稀褶红菇对SD大鼠腹腔注射LD50为406 mg/kgBW,95%可信限为348～473 mg/kgBW。病理学检查显示大鼠心脏、肝脏、肾脏均有损害,随剂量增加损害程度加重。结论 按照大鼠急性毒性（LD50）剂量分级亚稀褶红菇为中等毒性,相当于人的致死量为5 g/人。     

Vitreoretinal toxicity of basic fibroblast growth factor

Basic fibroblast growth factor (b-FGF) is one of the multifunctional growth factors with important therapeutic potential in the field of ophthalmology. It is also implicated in pathogenesis of vitreoretinal proliferative diseases. In the present study, we evaluated its vitreoretinal toxicity by means of clinical observation, electroretinography (ERG), and histopathology after injection of different doses of b-FGF into the vitreous of rabbit eyes. Doses of b-FGF up to 2 g per eye caused no toxicity; however, injection of 4 g or more resulted in sight-threatening vitreoretinal proliferative changes. This information is important for studies aimed at evaluating the therapeutic potential of b-FGF in retinal diseases.Despite some degree of vitreous organization and opacification, retinal folds, and small areas of traction retinal detachment, the amplitudes of ERGs were normal or even increased (hyperpolarization) in eyes which received 8 g of b-FGF.     

The Effects of Permeation Enhancers on the Surface Morphology of the Rat Nasal Mucosa: A Scanning Electron Microscopy Study

A rat model has been developed to compare relative morphological changes in the nasal mucosa after exposure to potential membrane permeation enhancers. Scanning electron microscopy was used to characterize gross structural and specific cellular changes following exposure. Micrographs of the rat nasal mucosa were scored in four categories: (1) mucosal surface integrity, (2) ciliary morphology, (3) mucus/extracellular debris, and (4) presence of red blood cells. The order of increasing morphological damage resulting from a 5-min exposure to each surfactant was 0.5% Solulan C-24 0.5% Solulan C-24/0.5% sodium tauro-24,25-dihydrofusidate (STDHF) < 0.5% STDHF < 1.0% STDHF 1.0% Laureth-9 < 1.0% sodium taurodeoxycholate 1.0% sodium deoxycholate. The changes observed in the mucosal morphology after exposure to the various surfactants are in general agreement with data in the literature. This model is able to compare rapidly the relative morphological effects on the mucosal membrane of different nasal formulations.     

Urinary arginine and ornithine in occupational exposure to 2-ethylhexanoic acid

Nine sawmill workers were divided into two groups according to their exposure to 2-ethylhexanoic acid, (EHA), a pesticide which has replaced the older pentochlorophenol. The men with lower exposure excreted 30±10 nmol EHA/mmol creatinine (mean ±SD,n=4) in urine samples taken after the workshift, whereas men with higher exposure excreted 1.8±1.6 mol EHA/mmol creatinine (mean±SD,n=5,p<0.01). The urinary ornithine and arginine concentrations were at the lower exposure 1.4±0.4 and 1.5±0.8 mol/mmol creatinine, respectively (mean±SD,n=4), and they increased significantly (p<0.01) to 4.5±2.5 and 3.2±1.5mol/mmol (mean±SD,n=5), respectively, at the higher exposure. This might have been caused by the inhibitory effect of EHA on urea synthesis which was partially compensated for by elevated arginine and ornithine concentrations to drive the urea cycle more efficiently.     

L—门冬酰胺酶前体脂质体对小鼠毒性及对实验性肿瘤作用

目的：研究L－门冬酰胺酶（L－Asparaginase,L-A)前体脂质体（Proliposome,PL)[L-APL]iv对小鼠的毒性及对荷瘤小鼠的抗肿瘤活性。方法：以小鼠的急性毒性和外周血中白细胞数及血小板数为指标观察药物对小鼠的毒性及以荷瘤小鼠的瘤重和生命延和工率观察药物的抗肿瘤活性;结果：L－APL iV对小鼠的急性毒性与L－A相比明显降低,L－APL对正常小鼠外周血中白细胞数,血小板数无明显影响,而相同剂量L－A对小鼠外周血中白细胞数,血小板数明显降低。与对照组相比,L－APL和L－Aip可明显延长腹水型小鼠移瘤L1210,P388的存活天数,与同剂量L－A相比,L－APL高剂量有明显延长腹水型小鼠移植瘤的存活天数作用。L－APL及L－A ip对小鼠移植瘤Heps,EC实体型的肿瘤生长具有明显的抑制作用,两者抑瘤作用相近。结论：L－APL对小鼠的毒性明显小于相同剂量的L－A,L－APL不仅保持了L－A的抗肿瘤活性,而且有明显的增效作用。     

却老壮骨片对家犬的长期毒性试验研究

观察却老壮骨片（壮骨片）连续给药后对家犬可能产生的毒性反应及性质。用壮骨片0．167、0．334、0．668mg/kg/d和甲基炔诺酮（0．154mg/kg/d)及尼尔雌醇（0.514mg/kg/d)给家犬连续口服180d,观察用药期间毒性反应及停药21天期间恢复情况。结果表明在用药150天后,壮骨片高剂量组和甲基炔诺酮高剂量组,动物体重增长虽略有减慢,但与对照组比较无显著性差异（P＞0．05）;其他各剂量组各功能检查未见明显变化。壮骨片在相当成人常用量74．2倍的大剂量下对家犬无毒性。     

脂质体阿霉素与阿霉素对小鼠毒性作用的比较研究

目的对比研究阿霉素和脂质体阿霉素对小鼠的毒性作用。方法将脂质体阿霉素与阿霉素分为几个不同的剂量组,观察静脉给药后两种剂型的急性LD50、小鼠血白细胞计数和血液生化变化及两药物组动物心、肝、肾、胃肠道等脏器的病理及心肌超微结构变化。结果脂质体载药可将药物LD50提高60％,动物毒性死亡率降低,动物血白细胞和血液生化改变明显减轻。病理检查提示脂质体组动物心、肾、胃肠道病理损害减轻,而肝、脾病理改变两药物组相仿。结论脂质体载药后可降低阿霉素对动物心、肾、胃肠道等重要脏器及全身的毒性作用。     

五氧化二钒的体外发育毒性研究

采用胚胎肢芽细胞进行原代微团培养 ,培养物经不同浓度的五氧化二钒 (V2 O5 )对细胞肢芽细胞经 5天增减形成细胞集落 ,V2 O5 对体外肢芽细胞的分化有明显抑制作用 ,并有较明显的剂量 -效应关系 ,其半数生长抑制浓度(ICV5 0 )和半分化抑制浓度 (ICD5 0 )分别为 12 .6和 1.6μg ml,V D值为 7.9。表明抑制细胞分化可能是V2 O5 致发育危害的重要作用机理