机构地区:[1]山西医科大学劳动卫生学教研室,太原030001
出 处:《中国药物与临床》2017年第11期1561-1565,共5页Chinese Remedies & Clinics
基 金:国家自然科学基金(81673143;30800899);山西省自然科学基金(2015011128);山西省出国留学基金(2016-057)
摘 要:目的探讨大鼠孕期暴露苯并[a]芘(B[a]P)对子代认知功能和脑源性神经营养因子(BDNF)的影响。方法选取清洁级SD雌鼠40只,随机分为5组,每组8只,分别为空白组、橄榄油组(溶剂组)、低剂量组(25 mg/kg)、中剂量组(50 mg/kg)、高剂量组(100 mg/kg)。孕期第17天起用B[a]P腹腔注射染毒,每天1次,连续3 d。子鼠出生第1,4,7,14,33天断头处死,每组取6只处死并取大脑皮质,第33天处死前眼眶采血,用酶联免疫吸附试验(ELISA)检测子鼠血浆及大脑皮质中BDNF蛋白表达。采用实时聚合酶链反应(q PCR)检测大脑皮质BDNF m RNA的相对表达量。子鼠出生28 d起进行Morris水迷宫试验,检测子鼠空间学习记忆能力。结果定位导航实验中,与空白对照组相比,前3 d 25、50、100 mg/kg组的逃避潜伏期降低(P<0.05),后2 d 100mg/kg组逃避潜伏期明显降低(P<0.01);与橄榄油组对比,100 mg/kg组的逃避潜伏期降低(P<0.05)。空间探索实验显示,与空白对照组对比,100 mg/kg组的穿越平台数和目标象限停留时间明显降低(P<0.05),与溶剂组对比,25、50、100 mg/kg组,穿越平台数和目标象限停留时间明显降低(P<0.05)。ELISA和q PCR实验结果显示:与空白对照组和橄榄油组对比,B[a]P染毒组的大脑皮质BDNF蛋白和BDNF基因的表达水平下降(P<0.05),50、100mg/kg组与空白对照组、低剂量组相比,子鼠血浆中BDNF蛋白水平下降(P<0.05),B[a]P 25、50、100 mg/kg组与溶剂对照组相比,子鼠血浆中BDNF蛋白水平明显下降(P<0.05)。结论孕期B[a]P暴露可导致子鼠学习记忆功能降低,这可能与BDNF表达下降有关,血浆BDNF可作为B[a]P暴露的标记物。Objective To investigate the effects of benzo[a]pyrene(B[a]P) exposure on cognitive function and brain-derived neurotrophic factor(BDNF) in offspring rats during pregnancy. Methods Forty clean-level female pregnant SD rats were randomly divided into 5 groups(n=8 each): blank control group, olive oil group(solvent group), low dose B[a]P group(25 mg/kg), medium-dose B[a]P group(50 mg/kg), and high-dose B[a]P group(100 mg/kg). Beginning from day 17 of the pregnancy, the B[a]P groups were given intraperitoneal injection of B[a]P once daily for consecutive3 days, while the solvent group was injected with olive oil in the same manner. The offspring rats were decapitated on postnatal days 1, 4, 7, 14 and 33. Cerebral cortex was obtained from six sacrificed rats of each group. Antemortem blood samples were collected from orbit on day 33. Enzyme-linked immunosorbent assay(ELISA) was used to examine the protein expression of BDNF in the plasma and cerebral cortex. The relative expression of BDNF m RNA in cerebral cortex was detected by q PCR. Morris water maze test was performed on day 28 after birth to measure the spatial learning and memory ability of the offspring rats. Results Compared with the blank control group, the escape latency was reduced(P〈0.05) in the first 3 days in the groups given 25 mg/kg, 50 mg/kg and 100 mg/kg B[a]P, and was significantly lower in the 100 mg/kg group(P〈0.01). Compared with the olive oil group, the escape latency in the 100 B[a]P mg/kg group was reduced(P〈0.05). Space exploration experiments showed that the time of spatial probe and numbers of traversing flat in 100 mg/kg group was significantly reduced compared with the blank control group( P〈0.05), and the time of spatial probe and numbers of traversing flat in 25 mg/kg, 50 mg/kg, and 100 mg/kg groups were signifi-cantly lower than those in the olive oil group(P〈0.05). ELISA and q PCR showed that the BDNF protein and m RNA expression in brain cortex of B [a]P groups were re
分 类 号:R114[医药卫生—卫生毒理学]
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