大鼠肝再生过程中增殖细胞核抗原的表达

目的:探讨大鼠肝再生过程中肝细胞增殖细胞核抗原(PCNA)表达的变化. 方法:建立肝切除动物模型,用免疫组织化学法、图像分析仪检测肝细胞PCNA的表达. 结果:PCNA强阳性肝细胞数及其总灰度值在肝大部切除后24 h明显增高,肝细胞阳性表达率在48 h达到峰值,至120 h趋于正常水平.结论:PCNA强阳性肝细胞呈规律性变化,提示残余肝可再生.     

全身体积描记法在大鼠呼吸系统试验中的应用

目的 应用全身体积描记法观察药物对大鼠呼吸指标的影响,对动物肺功能检测系统进行性能验证,为该技术用于药物安全药理学评价提供依据。方法 SD大鼠30只,雌雄各半,分为溶媒对照组、巴氯芬（30 mg/kg）组、茶碱（30 mg/kg）组,溶媒对照组给予等体积的0.5%羧甲基纤维素钠溶液。实验时将动物放入体积描记箱中,动物肺功能检测系统连续获取给药前至少60 min及给药后6 h内的数据,药后24 h至少连续采集60 min的数据,将每只动物给药前、给药后1、2、4、6、24 h均选取连续平稳的30个呼吸波,检测潮气量（TV）、每分钟通气量（MV）、呼吸频率（F）。结果 与溶媒对照组比较,巴氯芬组TV在给药后1、2、4、6、24 h显著增大（P<0.05）,呈先上升后下降趋势;F在药后2、4、6 h显著减慢（P<0.05）,呈先下降后上升趋势。大鼠给予30 mg/kg的茶碱后呼吸急促,药后1、2、4 h F明显加快、MV显著增加,均呈先上升后下降趋势,与溶媒对照组比较,药后1、2 h出现统计学差异（P<0.05）。结论 SD大鼠给予巴氯芬和茶碱后呼吸指标具有良好时间-反应趋势,可作为阳性药用于仪器的性能验证;肺功能检测系统能够准确记录清醒无束缚大鼠呼吸指标的变化情况,可用于呼吸系统安全药理学研究。     

Does status epilepticus modify the effect of ifenprodil on cortical epileptic afterdischarges in immature rats?

Background

Ifenprodil as a specific antagonist of NMDA receptors containing a dominant NR2B subunit exhibits age-dependent anticonvulsant action. Possible changes of this action due to status epilepticus (SE) elicited at early stage of development were studied using cortical epileptic afterdischarges (ADs) as a model.

Childhood polybrominated diphenyl ether (PBDE) exposure and executive function in children in the HOME Study

Prenatal exposure to polybrominated diphenyl ethers (PBDEs) have been reported to impair executive function in children, but little is known whether childhood PBDE exposures play a role. Using the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort in the greater Cincinnati area, we investigated the association between repeated measures of PBDEs during childhood and executive function at 8 years in 208 children and whether effect modification by child sex was present. We used child serum collected at 1, 2, 3, 5, and 8 years to measure PBDEs. The Behavior Rating Inventory of Executive Function was completed by parents to assess executive function at 8 years. We used multiple informant models to examine childhood PBDEs during several exposure windows. Null associations were observed between early childhood PBDEs and executive function. However, we observed significant adverse associations between a 10-fold increase in concurrent concentrations of BDE-28 (β = 4.6, 95% CI 0.5, 8.7) and BDE-153 (β = 4.8, 95% CI 0.8, 8.8) with behavioral regulation. In addition, PBDEs at 8 years were significantly associated with poorer emotional and impulse control. No associations were noted between childhood PBDEs and metacognition or global executive function. However, child sex significantly modified the associations, with significantly poorer executive function among males with higher concurrent BDE-153, and null associations in females. Our study findings suggest that concurrent PBDE exposures during childhood may be associated with poorer executive function, specifically behavior regulation. Males may also be more sensitive to adverse associations of concurrent PBDEs on executive function.     

Buccal micronucleus cytome assay in primary school children: A descriptive analysis of the MAPEC_LIFE multicenter cohort study

Background

Recent data support the hypothesis that genetic damage occurring early in life during childhood can play an important role in the development of chronic diseases in adulthood, including cancer.

Safety,tolerability and immunogenicity of intramuscular administration of PRP-CRM197 Hib vaccine to healthy Japanese children: An open-label trial

BackgroundJapan licensed the conjugate Haemophilus influenzae type b vaccine, Vaxem™ Hib, based on clinical studies using subcutaneous injection. The present study was performed to ensure this vaccine is suitable for intramuscular injection in Japanese children.MethodsThirty-one healthy 2–6-month-old infants received three doses of Vaxem™ Hib by intramuscular injection at 4-week intervals and a booster dose 1 year later, concomitant with routine infant (DTaP-IPV and pneumococcal) and toddler (measles–rubella) vaccines. Immunogenicity was assessed before and after the primary series and booster dose by enzyme-linked immunosorbent assay for anti-polyribosyl-ribitol-phosphate (PRP) antibodies. Safety was assessed by medical examination and diary cards completed by the subjects’ parents/legal guardians.ResultsThere were no vaccine-related serious adverse events or withdrawals; all children completed the study. Four weeks after the primary series, the geometric mean anti-PRP titer (GMT) was 19.68 μg/mL, and all children had seroprotective titers (≥0.15 μg/mL) that persisted until the booster dose. Proportions of titers indicative of long-term protection (≥1.0 μg/mL) were 100% after the primary series and 77.4% before the booster. Anamnestic responses to the booster had a GMT of 51.33 μg/mL, and 100% had titers ≥1.0 μg/mL. All but one subject reported injection site reactions as resolved within 3 days of vaccination; systemic reactions due to Hib and routine vaccines were also resolved within this period.ConclusionsVaxem™ Hib was generally well tolerated and immunogenic in Japanese children when administered by intramuscular injection in a three-dose primary series and as a booster with concomitant routine vaccines.Clinical trial registry: Registered on Clinical Trials.gov: NCT02074345.     

Potent effect of KISS1-54 DNA vaccine compared with KISS1-10 DNA vaccine in inhibiting the fertility of female rats

BackgroundMost studies on immunocastration currently focused on male animals. However, immunization of male animals does not completely inhibit sexual behavior and fertility. This study aimed to compare the immunocastration effect of KISS1 DNA vaccines encoding different lengths of kisspeptins in female rats for effective castration effects on both male and female rats.MethodsFifteen female rats were randomly divided into three groups. The rats in T1 group or T2 group was orally given respectively KISS1-54 or KISS1-10 DNA vaccines with fused tPA signal peptide, and the control group (Group C) was orally administered with empty vector vaccine, at a dose of 5 × 10⁹ CFU/rat at weeks 0, 3 and 6 of the study. Blood samples were collected by retroorbital bleeding before primary immunization and at weeks 3 and 9 after primary immunization.ResultsBoth KISS1-54 and KISS1-10 DNA vaccines induced the body’s humoral immune response, and the anti-kisspeptin antibody titres in the T1 group were significantly higher than that in T2 and C groups (p < 0.05). The rats in T1 group has lower serum kisspeptin and estradiol levels than those in T2 and C groups and smaller litter size of rats than those in the control group after mating (p < 0.05). No significant difference was observed between T2 and C groups. The levels of KISS1 and GPR54 mRNA in the hypothalamus and ovaries of the T1 group were significantly lower than that in control group. However, the levels of KISS1 mRNA in the T2 group were significantly lower than that in the control group only in ovaries (p < 0.05).ConclusionThe oral KISS1-54 DNA vaccine with fused tPA signal peptide was more effective than that KISS1-10 DNA vaccine in suppressing fertility of female rats.     

补中益气汤对脑缺血再灌注大鼠神经功能及梗死灶IL-1β和TNF-α表达的影响

目的:观察补中益气汤对脑缺血再灌注大鼠神经功能及梗死灶白细胞介素1β(interleukin-1β,IL-1β)、肿瘤坏死因子α(Tumour necrosis factor-α,TNF-α)表达的影响。方法:将60只SD大鼠随机分为假手术组、模型组、尼莫地平组、补中益气汤高剂量组、补中益气汤中剂量组、补中益气汤低剂量组,每组各10只。假手术组和模型组给予蒸馏水0.003 m L·(g·d)~(-1),尼莫地平组给予尼莫地平混悬液0.003 m L·(g·d)~(-1),补中益气汤高剂量组、补中益气汤中剂量组、补中益气汤低剂量组分别给予临床用药量的25倍、20倍、15倍水煎浓缩液灌胃,用量均按人与大鼠体表面积等效剂量折算,各组等容灌胃每日2次,灌胃6 d后,第7天采用Longa等线栓法复制大脑急性脑缺血再灌注损伤模型,在造模后12h进行神经功能缺损评分,测量脑指数,测定IL-1β、TNF-α含量,光镜下做脑组织病理形态学观察。结果:模型组大鼠脑指数降低、神经体征评分明显高于假手术组(P0.05);与模型组比较,给药组大鼠脑指数降低、神经体征明显改善,差异具有统计学意义(P0.01);与模型组比较,给药组大鼠脑组织IL-1β,TNF-α的含量明显降低,差异具有统计学意义(P0.01);与尼莫地平组比较,补中益气汤高剂量组脑指数明显降低,脑组织IL-1β、TNF-α的含量降低明显,差异均有统计学意义(P0.05)。病理组织学检查发现模型组大鼠脑组织出现不同程度的水肿,神经细胞轴索肿胀、断裂等缺血样改变,给药组大鼠上述病变明显减轻。结论:补中益气汤能明显改善脑缺血再灌注大鼠神经体征,可下调脑指数、降低脑组织IL-1β,TNF-α的含量,对脑缺血再灌注大鼠脑组织病理形态有较强的改善作用。     

黄芪和山药配伍微粉对糖尿病肾病大鼠抗氧化能力的影响

目的:观察黄芪和山药配伍微粉对糖尿病肾病大鼠抗氧化能力的影响,探讨其保护大鼠肾功能的作用机制。方法:采用单侧肾脏切除合并腹腔注射链脲佐菌素的方法诱导建立糖尿病肾病大鼠模型,将造模成功的45只大鼠随机分为模型对照组12只、卡托普利组11只、微粉低剂量组11只和微粉高剂量组11只,另取10只作为假手术对照组。卡托普利组灌胃卡托普利溶液剂量为13.5 mg·kg-1,微粉低剂量组灌胃微粉溶液,剂量为5.4 g·kg-1,微粉高剂量组灌胃微粉溶液,剂量为10.8 g·kg-1,假手术对照组和模型对照组大鼠灌胃等容积蒸馏水,每日1次,连续给药6周。给药结束后,采用免疫浊度法于计算24 h尿微量白蛋白量,运用全自动生化仪测定血清血尿素氮(Blood urea nitrogen,BUN)、血肌酐(Serum creatinine,Scr)含量,采用黄嘌呤氧化酶法测定血清超氧化物歧化酶(Superoxide Dismutase,SOD)活性,硫代巴比妥酸法测定血清丙二醛(malonaldehyde,MDA)含量。结果:微粉高剂量组能明显改善糖尿病肾病大鼠的一般状况,体质量较模型对照组明显增加,肾脏肥大指数明显减小,差异具有统计学意义(P0.05)。与假手术组比较,模型对照组大鼠24 h尿蛋白定量、血清BUN、血清Scr均明显升高,微粉高剂量组和卡托普利组较模型对照组降低,差异具有统计学意义(P0.05)。与假手术组比较,模型对照组血清SOD活性明显降低,血清MDA含量明显升高,微粉高剂量组和卡托普利组与模型对照组比较,血清SOD活性升高,血清MDA含量降低,差异具有统计学意义(P0.05)。结论:黄芪和山药配伍微粉可明显降低糖尿病肾病大鼠尿蛋白的排泄,降低血清BUN和Scr水平,升高血清SOD活性,降低MDA含量,具有明显的肾脏保护作用,黄芪和山药微粉对糖尿病肾病大鼠肾脏的保护作用与提高抗氧化能力有关。     

柴胡疏肝散对肝郁型代谢综合征大鼠糖脂代谢及胰岛素抵抗的影响

目的:观察柴胡疏肝散对肝郁型代谢综合征大鼠糖脂代谢及胰岛素抵抗的影响。方法:将40只大鼠随机分为普通饲料空白组和高脂饲料造模组,每组各20只。高脂饲料造模组给予高脂饲料喂养,采用束缚情志应激法造模。造模成功后,将普通饲料空白组随机分为普通饲料生理盐水组和普通饲料药物干预组,每组各10只;将高脂饲料造模组随机分为造模生理盐水组和造模药物干预组,每组各10只。高脂饲料造模组继续予高脂饲料喂养。普通饲料生理盐水组和高脂造模生理盐水组予0.01 ml·g~(-1)生理盐水灌胃;普通饲料药物干预组和高脂饲料造模药物干预组予柴胡疏肝散,按0.01 m L·g~(-1)灌胃,每日2次,连续4周。大鼠禁食12 h后,从眼眶静脉采血,离心取上清,测定三酰甘油(three acyl glycerin,TG)、血清总胆固醇(total cholesterol,TC)、低密度脂蛋白(low density lipoprotein cholesterol,LDL-C)和高密度脂蛋白(high density lipoprotein cholesterol,HDL-C)、空腹血糖(fasting plasma glucose,FBG)、空腹胰岛素(fasting insulin,FIN)。结果:高脂饲料造模组与空白组比较,HDL-C、TC、TG、FBG、FIN、胰岛素抵抗指数、体质量及腹围差异有统计学意义(P0.05)。造模药物干预组与造模生理盐水组大鼠比较,LDL-C、TC、FBG、FIN、胰岛素抵抗指数差异有统计学意义(P0.05)。结论:柴胡疏肝散能改善肝郁型代谢综合征大鼠的胰岛素抵抗,从而影响其糖脂代谢。