低分子质量魔芋甘露寡糖的长期毒性与遗传毒性研究（英文）

魔芋甘露寡糖是一种具有肠道菌群调节作用的新型食品添加剂.本研究首次通过酶解与有机溶剂沉淀法制备了低分子质量的甘露寡糖(聚合度2~7),并对这类寡糖进行了长期毒性与遗传毒性评价.在长期毒性试验中,以大鼠为实验对象,分低、中、高(2.25,5.25,7.50 g/kg)药物剂量组和阴性对照组,连续灌胃给药90天.一般状况观察、生化指标、血液学指标、病理学等与对照组比较均无显著性差异,而大体解剖观察发现,部分大鼠的肝脏与肾脏形态发生变化,但这些变化均在正常范围内,且其他各项指标差异均无统计学意义.此外,一系列实验包括小鼠骨髓微核实验、Ames试验、小鼠精子畸变试验均未发现低分子质量甘露寡糖有明显的遗传毒性.试验结果提示,本研究方法获得的低分子质量甘露寡糖在本实验条件下未发现长期毒性与遗传毒性.     

抑菌生亚急性毒性实验研究

本项研究的目的：是在一系列毒性试验的基础上进一步观察大鼠皮下给予由枯草芽孢杆菌ＢＳ２２４菌株制成的抑菌生后,对机体产生毒性反应的情况。结果表明：给药组大鼠饮食、活动正常。各项检测指标及病理组织学检查未发现异常,与对照组比较均无差异（Ｐ＞０．０５）,说明抑菌生无毒性反应。     

变异白色红花总黄酮提取物安全性毒理学评价

本文通过急性毒性试验、三项遗传毒性试验和30 d喂养试验,对变异白色红花总黄酮提取物(TFES)进行安全性毒理评价。结果表明,TFES对小鼠急性毒性试验,LD5010.0 g/kg·BW,按急性毒性剂量分级,属实际无毒物质;三项遗传毒性试验即Ames试验、小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验结果均为阴性;TFES对大鼠30 d喂养试验,动物未见明显的中毒症状和死亡,TFES各剂量组大鼠体重、总食物利用率、血清生化指标、血液学指标、脏器系数指标以及病理组织学等指标与对照组比较,无显著性差异。TFES在本实验条件下,未观察到明显毒性作用,为其进一步开发应用提供了安全依据。     

康脂口服液毒理学的研究

通过大、小鼠的急性毒性试验和大鼠的急性毒性试验和大鼠蓄积毒性试验及遗传毒性试验表明,康脂口服液的ＬＤ５０大于１０．００ｇ／ｋｇ．ｂｗ,实属无毒物质;蓄积毒性试验３表明,本品蓄积系数Ｋ〉５,为弱蓄积;遗传毒性试验得知,Ａｍｅｓ试验无遗传毒性,对小鼠骨髓嗜多染红细胞微核及小鼠精子畸形试验也均未产生影响,说明本品长期服用比较安全。     

成团泛菌低分子脂多糖的急性毒性、刺激性、致敏性及遗传毒性评估

本研究对成团泛菌低分子脂多糖(Pantoea agglomerans lipopolysaccharide,LPSp)的安全性进行初步评估.本研究采用一次限量法,用昆明种小鼠进行LPSp急性经口毒性试验,了解LPSp的急性毒性;采用新西兰兔分别进行LPSp急性和多次皮肤刺激性试验以及急性眼刺激性试验,了解LPSp的皮肤和粘膜刺激性;采用豚鼠进行LPSp皮肤变态反应试验,了解LPSp的致敏性;应用平板掺入法进行鼠伤寒沙门氏菌/回复突变试验和小鼠骨髓细胞微核试验考察LPSp的遗传危害.急性毒性试验结果显示,LPSp对小鼠经口一次灌胃的LD50大于5 000 mg/kg体重,属实际无毒级别;LPSp急性和多次皮肤刺激性试验以及急性眼刺激性试验结果显示,皮肤刺激和眼刺激积分均为0分,LPSp对皮肤无刺激性、对眼睛无急性刺激性;在皮肤变态反应试验中,LPSp在各观察时间点的皮肤变态反应积分均为0分,其致敏率均为0%,说明LPSp对豚鼠无致敏性; LPSp的鼠伤寒沙门氏菌/回复突变试验结果呈阴性(P>0.05);LPSp的小鼠骨髓细胞微核试验结果亦呈阴性,LPSp 各剂量组的微核发生率与阴性对照组未见统计学差异(P>0.05),而与阳性对照组有明显差异(P<0.01).本研究结果表明,在本实验剂量范围内,LPSp对小鼠经口毒性极低,属实际无毒级别,对家兔皮肤和眼睛无明显刺激性,对豚鼠无致敏性,对所试菌株和小鼠体细胞无诱变性和致突变性.     

骆驼刺提取物大鼠灌胃长期毒性实验研究

观察骆驼刺提取物对SD大鼠的长期毒性反应。采用SD大鼠120只,雌雄各半,按体重随机分为对照组及低、中、高剂量药物组,连续灌胃3个月,对照组给予羧甲基纤维素钠,检查血液学、血生化、电解质及组织病理学。结果显示各组大鼠给药期间未出现异常反应,高剂量雄性大鼠体重下降,与对照组比较,中、高剂量组的LYMPH、NEUT、RBC、HGB、PLT、BUN、K+、Na+升高,低、中、高剂量组的ALB、CHO、GLU降低,均在正常范围,组织病理学检查无明显变化,未见明显毒性反应剂量为1.0 g/(kg·d)[相当于生药22.7 g/(kg·d)]。本研究证明骆驼刺提取物对大鼠无明显毒副作用。     

梨果仙人掌红花品系的毒性研究

通过对梨果仙人掌红花品系的小鼠急性毒性试验、小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验研究,梨果仙人掌红花品系雌、雄小鼠LD50均大于170．0g／kgBw,属无毒物质;小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验结果均为阴性。因此在本次实验条件下,梨果仙人掌红花品系为无毒物质,未显示有遗传毒性作用。     

人参花食用安全性研究

目的:对人参花食用安全性进行毒理学评价.方法:采用大鼠经口急性毒性试验、遗传毒性试验(Ames试验、小鼠骨髓细胞微核试验、小鼠精子畸形试验)、大鼠30 d喂养试验.结果:雌、雄大鼠经口最大耐受剂量(MTD)均大于17.4 g/kg·bw.3项遗传毒性试验结果均为阴性.在大鼠30 d喂养试验中,6.0 g/kg·bw,3.0 g/kg·bw及1.5g/kg· bw 3个剂量组的实验动物均生长发育良好,体重、摄食量、饮水量、血液学、血液生化学、脏器系数及病理组织学相关指标均未见异常变化.结论:人参花属于实际无毒物,未见遗传毒性,长期服用是安全的.     

一株人源链球菌作为潜在益生菌的安全性评价CSCD

目的对分离自健康儿童口咽部1株对金黄色葡萄球菌、大肠埃希菌等致病菌具有拮抗作用的链球菌C-17株做体内安全性评估,为今后呼吸道微生态制剂的研发与应用提供基础。方法通过急性毒性及亚急性毒性试验,给予小鼠口服不同剂量的链球菌C-17株菌液,观察动物是否出现死亡、中毒现象以及体质量、采食量、血常规指标、生化指标等的变化,然后对结果进行统计学分析。结果实验组小鼠均未出现死亡、中毒的现象,其体质量、采食量和脏器指数同对照组相比差异无统计学意义(均P>0.05)。同时,在亚急性毒性试验中,各剂量组小鼠的血常规及生化指标与对照组相比差异无统计学意义(均P>0.05),各脏器也未出现任何病理学变化。结论口服链球菌C-17株对小鼠并无毒性作用,具有良好的体内安全性,但作为呼吸道微生态制剂还需做呼吸毒性试验。     

热感赛比斯坦颗粒毒理学实验研究

观察热感赛比斯坦颗粒对小鼠的急性和大鼠长期毒性反应。将热感赛比斯坦颗粒生药浸膏液干燥,粉碎,以最大浓度及小鼠最大给药体积对小鼠灌胃,进行最大耐受量试验,观察两周之内出现的急性毒性反应。采用SD大鼠分别给予37.50 g/(kg·d)、12.50 g/(kg·d)、3.75 g/(kg·d)药物灌胃,空白组给予同等体积的蒸馏水,进行长期毒性试验。在给药30 d、停药15 d测定生化、血象指标、脏器系数和各主要脏器病理切片。急性毒性试验测得小鼠最大耐受量为299.70 g/kg,无死亡现象,解剖后发现小鼠各主要脏器无肉眼可见病变。长期毒性试验给药及恢复期间各组大鼠体重无统计学差异。血液学、血生化及脏器系数检查,给药组与对照组之间个别指标有差异,无毒性意义。主要脏器的病理组织学检查,未见明显病理改变。本研究证明热感赛比斯坦颗粒临床成人拟用给药剂量远低于其毒性剂量,安全性良好。     

Novel in vitro and in vivo inhibitors of prolyl endopeptidase

Inhibition of prolyl endopeptidase by Z-cyclohexyl prolinal and Z-indolinyl prolinal occurs with slow, tight binding inhibition and K_i values of 2 – 3 nM. In vivo enzyme inhibition is also observed with a half time for recovery of enzyme activity of 3 – 4 h.Inhibition of prolyl endopeptidase by Z-cyclohexyl prolinal and Z-indolinyl prolinal occurs with slow, tight binding inhibition and K_i values of 2 – 3 nM. In vivo enzyme inhibition is also observed with a half time for recovery of enzyme activity of 3 – 4 h.     

Dietary phytoestrogens and cancer: in vitro and in vivo studies

Thirty postmenopausal women (11 omnivores, 10 vegetarians and 9 apparently healthy women with surgically removed breast cancer) were investigated with regard to the association of their urinary excretion of estrogens, lignans and isoflavonoids (all diphenols) with plasma sex hormone binding globulin (SHBG). A statistically significant positive correlation between urinary total diphenol excretion and plasma SHBG was found which remained statistically significant after elimination of the confounding effect of body mass determined by body mass index (BMI). Furthermore we found a statistically significant negative correlation between plasma SHBG and urinary excretion of 16α-hydroxyestrone and estriol which also remained significant after eliminating the effect of BMI. Furthermore we observed that enterolactone (Enl) stimulates the synthesis of SHBG by HepG2 liver cancer cells in culture acting synergistically with estradiol and at physiological concentrations. Enl was rapidly conjugated by the liver cells, mainly to its monosulfate. Several lignans and the isoflavonoids daidzein and equol were found to compete with estradiol for binding to the rat uterine type II estrogen binding site (the s.c. bioflavonoid receptor). It is suggested that lignans and isoflavonoids may affect uptake and metabolism of sex hormones by participating in the regulation of plasma SHBG levels and in this way influence their biological activity and that they may inhibit cancer cell growth like some flavonoids by competing with estradiol for the type II estrogen binding sites.     

Phagocytosis by carp granulocytes; in vivo and in vitro observations

The phagocytic ability of carp (Cyprinus carpio L.) granulocytes was evaluated in vivo and in vitro. In suspensions of head kidney cells, neutrophil granulocytes incorporated both latex beads and coccidian merozoites. In intestinal tissues from carp with a Goussia carpelli infection, all granulocyte cell types (neutrophils and cells of the basophilic-eosinophilic complex) phagocytosed cell detritus and coccidian developmental stages, mainly merozoites.     

单增李斯特菌胎盘感染的体内外模型研究进展

单核细胞增生李斯特氏菌（Listeria monocytogenes）是重要的食源性致病菌,能引发人类的李斯特菌病,是全球公共卫生问题之一。该菌易感染孕妇,引起胎儿和新生儿的侵袭性李斯特菌病,严重威胁母婴健康。因此,建立有效的单增李斯特菌感染胎盘体内外模型,解析和探究单增李斯特菌经胎盘感染机制,是预防和控制单增李斯特菌感染母婴的关键所在。本文综述了可用于研究单增李斯特菌母婴感染的体内外胎盘模型,总结和讨论了各类模型的优势和局限性;并着重分析了体外三维胎盘屏障模型在单增李斯特菌感染方面的研究进展和未来研究方向。以期为深入解析该菌经胎盘感染的途径、发病机制提供支持,并为预防和控制母婴李斯特菌病提供科学参考。     

Trichinella spiralis and Trichinella pseudospiralis induce collagen synthesis by host fibroblasts in vitro and in vivo

Immunoperoxidase staining of muscle infected with Trichinella spiralis for murine collagen types I and IV provided both qualitative and quantitative evidence of extensive synthesis of both types of collagen by fibroblasts in infected muscle compared to that seen uninfected muscle. Moreover, fibroblasts in muscle infected with T. pseudospiralis, a nonencapsulating species, showed significantly less staining for both types of collagen compared to muscle from mice infected with T. spiralis. Analysis of collagen composition of isolated nurse cells using an ELISA specific for either type I or type IV murine collagen suggested that of these 2 types of collagen, only type IV basement membrane collagen is found in Trichinella capsular collagen. Excretory/secretory products of T. spiralis and T. pseudospiralis induced extensive synthesis of exclusively type IV collagen by 3T3 murine fibroblasts in vitro.     

黄芩苷对嗜水气单胞菌生物膜形成的影响及体内外的抑菌作用

[目的] 探讨中药单体黄芩苷对嗜水气单胞菌在体内外生长及生物膜形成的影响。[方法] 体外实验中,利用牛津杯法检测抑菌圈直径,结晶紫法检测生物膜的形成,通过泳动实验检测黄芩苷对嗜水气单胞菌运动性的影响,紫外吸收法检测细胞膜完整性,用透射电镜技术观察黄芩苷对细菌形态的影响。体内实验利用草鱼为对象检测黄芩苷对嗜水气单胞菌增殖的影响。[结果] 黄芩苷在体外对嗜水气单胞菌有明显的抑菌效果,通过对生物膜的研究发现黄芩苷对生物膜形成具有抑制作用,并同时抑制其运动性。同时黄芩苷可以破坏细胞结构,并增加了细胞膜通透性。体内实验结果显示黄芩苷对嗜水气单胞菌具有清除作用,且具有一定的浓度依赖性。[结论] 黄芩苷在体内外均具有抑制嗜水气单胞菌增殖的作用,有望在水产养殖病害防治工作中得到应用。     

A mechanism for heterogeneous endothelial responses to flow in vivo and in vitro

Exposure of endothelium to a nominally uniform flow field in vivo and in vitrofrequently results in a heterogeneous distribution of individual cell responses. Extremes in response levels are often noted in neighboring cells. Such variations are important for the spatial interpretation of vascular responses to flow and for an understanding of mechanotransduction mechanisms at the level of single cells. We propose that variations of local forces defined by the cell surface geometry contribute to these differences. Atomic force microscopy measurements of cell surface topography in living endothelium both in vitro and in situ combined with computational fluid dynamics demonstrated large cell-to-cell variations in the distribution of flow-generated shear stresses at the endothelial luminal surface. The distribution of forces throughout the surface of individual cells of the monolayer was also found to vary considerably and to be defined by the surface geometry. We conclude that the endothelial three-dimensional surface geometry defines the detailed distribution of shear stresses and gradients at the single cell level, and that there are large variations in force magnitude and distribution between neighboring cells. The measurements support a topographic basis for differential endothelial responses to flow observed in vivo and in vitro. Included in these studies are the first preliminary measurements of the living endothelial cell surface in an intact artery.     

斑马鱼胸苷酸合成酶与自身mRNA的相互作用

斑马鱼(zebrafish,Danio rerio)是生物学领域中公认的研究脊椎类生物的模式生物.胸苷酸合成酶(thymidylate synthase,TS)是DNA从头合成的限速酶,多年来一直作为肿瘤化疗的重要靶酶.前期的研究表明,人和大肠杆菌中TS能与自身的mRNA结合,在翻译水平上具有反馈抑制自调控现象.斑马鱼作为药物模型的研究已成为热点研究领域,为了探讨斑马鱼的胸苷酸合成酶的调控规律,以及与人TS的相关性,利用原核表达,纯化获得高均一性斑马鱼TS蛋白,采用凝胶迁移研究了TS和其mRNA的体外结合,采用免疫共沉淀:RT-PCR技术研究了它们在体内的相互作用,实验结果表明,斑马鱼的TS在体内外均与自身的mRNA存在特异性的相互作用.研究说明,斑马鱼和人的TS具有高度生物学过程相关性,为构建斑马鱼抗肿瘤药理模型提供了理论基础.