虫草素抑制哮喘大鼠支气管上皮细胞间充质转化

目的 考察虫草素(Cor)抑制哮喘大鼠上皮细胞间充质转化的作用机制.方法 将大鼠随机分为4组(n=10):对照组、模型(OVA)组、OVA+10 mg/kg Cor组、OVA+50 mg/kg Cor组.治疗7 d后,检测支气管肺泡灌洗液(BALF)中的细胞计数,苏木精-伊红(HE)染色评价气道炎性反应和气道重塑程度,...     

黄连解毒汤对变应性鼻炎大鼠TLR4/NF-κB信号通路及黏膜杯状细胞的影响

目的:探究黄连解毒汤对变应性鼻炎大鼠黏膜杯状细胞及Toll样受体4(TLR4)/核因子κB(NF-κB)信号通路的影响.方法:卵白蛋白制备变应性鼻炎大鼠模型,模型制作成功后分为:模型组,黄连解毒汤低、中、高剂量组,以及阳性对照组.黄连解毒汤低、中、高剂量组分别按5、10和20 g/kg生药量灌胃,阳性对照组给予丙酸氟替...     

AcCystatin减轻卵清蛋白诱导的小鼠变应性鼻炎病变和促炎细胞因子分泌

目的观察广州管圆线虫半胱氨酸蛋白酶抑制剂(AcCystatin)对卵清蛋白(OVA)诱导的变应性鼻炎小鼠的影响。方法将24只8周龄雌性BALB/c小鼠随机分为空白对照组、 OVA变应性鼻炎致敏组和AcCystatin治疗组。OVA组以OVA为变应原,氢氧化铝为佐剂进行腹腔注射,第15天后OVA滴鼻建立小鼠AR模型;AcCystatin组在致敏时腹腔注射30μg AcCystatin,并在第15天后将含有OVA的混悬液中溶入AcCystatin滴鼻治疗;对照组均以PBS替代OVA。末次滴鼻激发后,按照生物学评分标准对3组小鼠的症状进行评分,HE染色观察小鼠鼻黏膜的病变情况,ELISA检测小鼠血清OVA-IgE、白细胞介素4(IL-4)、 IL-5、 IL-6、 IL-10和γ干扰素(IFN-γ)的分泌水平。结果与对照组相比,OVA组小鼠生物学评分明显增加,AcCystatin组小鼠生物学评分较OVA组明显降低。镜下观察OVA组小鼠鼻黏膜纤毛明显脱落,杯状细胞增生,基底膜增厚、组织水肿且黏膜下小血管扩张,而AcCystatin组小鼠鼻黏膜病变明显减轻。同时OVA组血清中OVA-IgE、 IL-4、 IL-5、 IL-6水平较对照组明显升高,IL-10水平降低;与OVA组相比,AcCystatin组OVA-IgE、 IL-4、 IL-5、 IL-6和IL-10水平显著降低。结论AcCystatin减轻OVA诱导的小鼠变应性鼻炎病变和炎性细胞因子分泌。     

RAI1脱敏干预影响变应性鼻炎大鼠模型ECP表达和Th1-Th2分化的机制

目的探究探针RAI1脱敏干预影响变应性鼻炎大鼠模型ECP表达和Th1-Th2分化的机制方法卵白蛋白(OVA)诱导雌性Sprague-dawley大鼠构建过敏性鼻炎(AR)模型。并进行构建沉默RAI1 mRNA质粒载体,脑内注射至AR模型大鼠体内。通过蛋白质印迹法检测Th1-Th2相关因子的蛋白表达情况;通过q RT-PCR分析各组大鼠中维甲酸诱导蛋白RAI1的m RNA表达情况;通过记录大鼠鼻炎行为评估变应性鼻炎症状;通过酶联免疫吸附试验检测各组大鼠血清中ECP、IgE含量。结果大鼠搔鼻挠嘴、打喷嚏行为AR模型组较对照组、RAI1干预组频繁(P0.05),说明AR模型建立成功。RAI1干预组(1.02±0.01)较AR模型组(2.85±0.25)、对照组(2.69±0.11)相比,RAI1mRNA表达降低(P0.05),说明病毒载体构建成功,RAI1蛋白表达受到抑制。Th1相关因子IL-2、IFN-γ的蛋白表达AR模型组较对照组、RAI1干预组低(P 0.05)。Th2相关因子IL-4、IL-5的蛋白表达AR模型组较对照组、RAI1干预组高(P0.05)。经酶联免疫吸附检测ECP、IgE含量,AR模型组(3.11±0.23、29.51±3.64)较对照组(1.62±0.18、13.72±2.68)、RAI1干预组(1.85±0.14、17.66±2.16)升高(P 0.05)。结论RAI1脱敏干预会降低ECP蛋白表达,平衡Th1-Th2生物功能,对变应性鼻炎具有治疗效果,减轻鼻炎症状。     

鼻炎清颗粒治疗变应性鼻炎的免疫机制研究

目的:观察鼻炎清颗粒治疗大鼠变应性鼻炎(AR)后,细胞因子、血清特异性IgE和嗜酸粒细胞阳离子蛋白(ECP)的水平,了解该药治疗AR的部分免疫学机制.方法:用卵清蛋白(OVA)、氢氧化铝、百白破疫苗联合致敏大鼠建立变应性鼻炎动物模型,鼻炎清颗粒灌胃给药2周后,观察鼻黏膜组织学变化,ELISA法检测血清细胞因子IL-4、 IFN-γ、 IgE 和ECP的水平.结果:光镜观察发现,模型组鼻黏膜上皮细胞脱落、水肿、血管扩张、腺体增生,固有层内可见大量嗜酸性粒细胞、肥大细胞浸润,治疗组大剂量和中剂量组及阴性对照组则无上述改变.治疗组大、中剂量组血清IL-4水平分别为(10.30±4.41) ng/L 和(12.42±6.55) ng/L,明显低于模型组(17.62±6.10) ng/L,有统计学差异(P＜0.01或P＜0.05);而IFN-γ水平分别为(34.19±6.16) ng/L和(27.92±6.47) ng/L,明显高于模型组(19.33±5.63) ng/L(P＜0.01);3种剂量组的血清IgE水平分别为(26.46±6.12) μg/L、 (49.11±4.48) μg/L和(70.68±7.59) μg/L,与阳性模型组(81.03±7.54) μg/L,相比较有统计学差异(P＜0.01或P＜0.05);血清ECP水平分别为(1.48±0.25) μg/L,(2.30±0.56) μg/L和(3.05±1.27) μg/L,与阳性模型组(4.23±1.20) μg/L比较,大、中剂量组有统计学意义(P＜0.01或P＜0.05),小剂量组无统计学意义.结论:鼻炎清颗粒通过调节Th1和Th2细胞因子的表达,纠正失衡的Th1/Th2的细胞因子网络,降低血清特异性IgE和ECP水平和抑制炎症细胞在鼻黏膜的聚集,防止其脱颗粒,对变应性鼻炎产生治疗作用.     

变应性鼻炎大鼠动物模型的建立及评价

目的建立和评价SD大鼠变应性鼻炎模型。方法将SD大鼠随机分为对照组和模型组,模型组给予卵白蛋白(OVA)配合佐剂氢氧化铝全身致敏和局部致敏,建立SD大鼠变应性鼻炎模型;对照组以生理盐水代替OVA;HE染色检测鼻粘膜组织形态学变化;Wright’s染色检测模型组鼻腔分泌物和鼻粘膜组织嗜酸性粒细胞的表达;酶联免疫吸附测定法(ELISA)检测外周血IgE水平;通过行为学总积分对动物模型进行评价。结果模型组鼻粘膜组织纤毛脱落、倒伏,粘膜下腺体数量明显增加;模型组鼻腔分泌物中检测到大量嗜酸性粒细胞;模型组外周血IgE水平较对照组明显增高,具有统计学意义(P0.05);滴鼻后模型组喷嚏、抓鼻的次数及流涕等行为学总积分较对照组组明显增高,具有统计学意义(P0.05)。结论通过卵清蛋白配合佐剂氢氧化铝基础致敏和强化致敏,可成功建立SD大鼠变应性鼻炎动物模型,具有操作简单、重复性好、成功率高的优点,为今后变应性鼻炎的病变研究提供了有效的方法及组织形态学依据。     

艾叶挥发油治疗大鼠变应性鼻炎的实验研究

目的:观察艾叶挥发油对变应性鼻炎(AR)大鼠血清中IgE、IL-4和IL-5含量的影响。方法:60只SD大鼠按体重随机分为正常对照组、模型组、治疗组和阳性药对照组,每组10只。实验组用卵蛋白(OVA)、氢氧化铝和灭活百日咳杆菌皮下注射致敏,用10%的卵蛋白生理盐水溶液滴鼻激发,建立AR模型。正常对照组以等量生理盐水代替。治疗组和阳性药对照组分别灌胃给予艾叶挥发油和氯雷他定治疗10天,正常对照组用橄榄油代替药物;另外20只大鼠用于被动皮肤过敏原试验(PCA),检验大鼠模型制备及治疗情况;用ELISA法测定各组大鼠外周血清IL-4、IL-5和IgE含量。结果:模型组大鼠鼻喷嚏平均次数明显多于正常对照组、治疗组和阳性对照组(P<0.05);模型组大鼠PCA试验阳性率为92%,其余三组全部表现为阴性;模型组IgE均显著高于正常对照组(P<0.05);治疗组IgE、IL-4、IL-5均显著低于模型组(P<0.05);治疗组各项指标与阳性对照组比较差异无统计学意义。结论:艾叶挥发油可降低AR大鼠血清中IL-4、IL-5和IgE含量,减轻鼻粘膜变应性炎症。     

白皮杉醇通过激活Nrf2/HO-1通路减轻糖尿病大鼠视网膜氧化应激反应

目的 探讨白皮杉醇对糖尿病大鼠视网膜的影响及机制.方法 雄性SD大鼠30只,按60 mg/kg腹腔一次性注射链脲佐菌素(streptozotocin,STZ)诱导糖尿病模型.模型诱导成功后,糖尿病大鼠随机分成三组:糖尿病组、白皮杉醇组(200 mg/kg)及二甲双胍组(75 mg/kg,阳性对照)灌胃治疗,另取10只正常大鼠作为对照组.12周后,检测各组大鼠血糖、体重、丙二醛(MDA)及超氧化物歧化酶(SOD)含量;HE染色检测大鼠视网膜神经节细胞(retinal ganglion cell,RGC)数量,免疫荧光染色及Western blot检测大鼠肾脏核因子NF-E2相关因子(nuclear factor erythroid-2-related factor-2,Nrf2)、血红素氧合酶-1(heme oxygenase-1,HO-1)蛋白表达.结果 与对照组相比,糖尿病组血糖、MDA含量及Nrf2表达明显增加,SOD活性、HO-1表达及RGC数量明显下降.而与糖尿病组相比,白皮杉醇组血糖、MDA含量明显降低,SOD活性、Nrf2和HO-1表达及RGC数量明显增加.结论 白皮杉醇减轻糖尿病大鼠视网膜神经节细胞损伤,与激活Nrf2/HO-1信号通路相关.     

氟西汀对野百合碱诱导Wistar大鼠肺动脉和右心室构型重建的影响

目的 研究氟西汀对野百合碱(monocrotaline,MCT)诱导Wistar大鼠肺动脉和右心室构型重建的影响.方法 应用野百合碱建立大鼠肺动脉高压模型,40只Wistar大鼠均分为4组:对照组(control)、模型组(MCT)、氟西汀低剂量2mg/kg组(MCT+F2)和氟西汀高剂量lOmg/kg组(MCT+F1...     

青藤碱和甲氨蝶呤对降植烷诱导的关节炎大鼠血清IL-10和TNF-α的影响

目的:探讨青藤碱和甲氨蝶呤对降植烷诱导的关节炎大鼠(pristane induced arthritis,PIA)血清白细胞介素-10(interleuk in-10,IL-10)和肿瘤坏死因子-α(tumor necrosis factor-,αTNF-α)的影响。方法:将40只Lew is大鼠随机平均分为5组,即正常组、模型组、青藤碱组、MTX组、青藤碱 MTX组,除正常组大鼠,在其它大鼠尾根部位皮内注射0.2m l/只剂量的降植烷以建立PIA模型,同时口服青藤碱(120mg.kg-1.d-1)和/或MTX(3.8mg.kg-1.w-1)共8w。正常对照组大鼠皮内注射等量的生理盐水并口服生理盐水(10mg/kg/w)。给药8w后采血,用放射免疫分析检测血清IL-10和TNF-α的水平。结果:MTX组大鼠血清IL-10(及TNF-α)水平均明显低于模型组大鼠(P<0.05);模型组大鼠血清TNF-α含量明显高于正常对照组和含MTX治疗组(P<0.05),与单用青藤碱治疗组比较无显著性差异。结论:甲氨蝶呤可能对PIA大鼠血清IL-10和TNF-α均有明显抑制作用。     

Development in in vitro toxicology

There are three principal pressures driving the development of in vitro toxicology: (1) the need for more efficient testing systems to cope with the large number of xenobiotics currently being developed; (2) public pressure to reduce animal experimentation; and (3) a need for a better understanding of the mechanisms of toxicity. Within this, in vitro toxicology is focused on local, systemic, and target-organ toxicity. It is becoming increasingly apparent that a step or decision-tree approach using input of a variety of experimental data (physicochemical properties, biokinetics, cytotoxicity) provides the most efficient system for predicting toxicity. Examples of the use of in vitro toxicity systems for prediction of systemic toxicity and target-organ (liver) toxicity are presented.Originally presented at ECCP 93.     

Age-related changes in polyamines in memory-associated brain structures in rats

Polyamines putrescine, spermidine and spermine are positively charged aliphatic amines and have important roles in maintaining normal cellular function, regulating neurotransmitter receptors and modulating learning and memory. Recent evidence suggests a role of putrescine in hippocampal neurogenesis, that is significantly impaired during aging. The present study measured the polyamine levels in memory-related brain structures in 24- (aged), 12- (middle-aged) and 4- (young) month-old rats using liquid chromatography/mass spectrometry and high performance liquid chromatography. In the hippocampus, the putrescine levels were significantly decreased in the CA1 and dentate gyrus, and increased in the CA2/3 with age. Significant age-related increases in the spermidine levels were found in the CA1 and CA2/3. There was no difference between groups in spermine in any sub-regions examined. In the parahippocampal region, increased putrescine level with age was observed in the entorhinal cortex, and age did not alter the spermidine levels. The spermine level was significantly decreased in the perirhinal cortex and increased in the postrhinal cortex with age. In the prefrontal cortex, there was age-related decrease in putrescine, and the spermidine and spermine levels were significantly increased with age. This study, for the first time, demonstrates age-related region-specific changes in polyamines in memory-associated structures, suggesting that polyamine system dysfunction may potentially contribute to aged-related impairments in hippocampal neurogenesis and learning and memory.     

休克过程中肾上腺髓质素变化的研究进展

Adrenomedullin (AM) is a new peptidergic regulator of vascular function. AM serves as a hormone, which has many biological properties, plays an important role in the many pathophysiological processes, especially shock. This review will highlight the structure, biological properties of AM and the relationship between AM and shock.     

Seasonal variations in acute toxoplasmosis in pregnant women in Slovenia

Between December 1999 and December 2004, 40 081 pregnant women were examined for toxoplasmosis with Toxo-IgG, Toxo-IgM enzyme immunoassay. Women with positive results were then retested with the Toxo-IgG avidity assay for recent toxoplasmosis. Recent acute toxoplasmosis in pregnant women was found to be significantly more frequent (p < 0.01) during winter than summer. The incidence of acute toxoplasmosis during winter-spring was also significantly more frequent (p < 0.025) than summer-autumn. This phenomenon should be taken into account when formulating preventive measures for toxoplasmosis, especially for pregnant women.     

Secular change in menarche in women in Madrid

The age at menarche was estimated by recollection in 1617 women between the ages of 18 and 60 in Madrid and a nearby suburb, Pinto. The population of Pinto is working-class and the Madrid group, taken from residential neighbourhoods , belongs to the upper middle class. In both groups we found a diminution in average age at menarche, from 14.04 to 13.02 years in Madrid and from 14.55 to 13.16 years from about 1935 to about 1965 in Pinto. These changes have been more intense in the group which is less well-off economically, where living conditions have varied much more drastically.     

Uteroglobin in the developing rabbit conceptus in vivo and in vitro

Summary Uteroglobin (UGL) was measured in day- 4 to day-10 rabbit conceptuses by a competitive ELISA. Levels in blastocyst fluid, tissues, coverings and in the early fetus were determined separately. The total amount of UGL increased from 18.4 ng to 6.8 g per conceptus. The UGL content of individual day-6 blastocysts was studied in vitro. Culturing was carried out up to 60 h in Ham's F10 medium with polyvinylpyrrolidone as macromolecular component, with and without progesterone, and with progesterone plus estradiol. UGL was determined in the blastocyst fluids, tissues with coverings and in the culture media. After labelling with [³⁵S]-methionine, protein patterns of total blastocysts and of culture media were analysed by two-dimensional gel electrophoresis and fluorography. The morphology of cultured blastocysts was examined by electron microscopy. During 60 h of culture, the blastocysts expanded in diameter by 84%, and released 19% of their initial UGL content into the medium, independent of the hormonal substitution. Neither de novo synthesis, nor degradation of UGL was found: the protein remained unlabelled in fluorography, and its total quantity was not significantly different from that of non-cultured controls. Trophoblast, endoderm and embryoblast cells showed well preserved cell organelles and intercellular junctions, while the morphological differentiation of the germ layer was inhibited.