中文摘要：

目的通过观察亚慢性染毒苯并[a]芘（B[aJP）对大鼠海马神经细胞Bax、Bcl．2、Caspase3、Caspase6和Caspase9等凋亡相关基因mRNA和蛋白表达水平及Caspase3、Caspase6和Caspase9蛋白活性的变化，探讨B[a]P诱发神经细胞凋亡的神经毒理学机制。方法选取健康雄性sD大鼠52只，按照初步神经行为测试结果随机分为空白对照组、溶剂对照组及1．00、2．50、6．25mg／kgB[a]P染毒组，隔日腹腔注射B[a]P，持续90d。Morris水迷宫法测试大鼠的学习记忆能力，流式细胞术检测大鼠海马神经细胞凋亡情况，荧光定量PCR法、蛋白免疫印迹法（Westernblot）分别检测基因mRNA和蛋白表达水平，分光光度法检测蛋白活性。结果与空白对照组、溶剂对照组和1．00mg／kg染毒组比较，2．50和6．25mg／kg染毒组平均逃避潜伏期明显升高，穿越平台次数明显降低，6．25mg／kg染毒组平台象限滞留时间和平台象限滞留百分比明显降低，差异均有统计学意义（P〈0．05）。早期凋亡率呈随染毒剂量增加而增高的趋势（P趋势〈0．05），其中1．00、2．50和6．25mg／kg染毒组早期凋亡率明显高于空白对照和溶剂对照组，差异有统计学意义（P〈0．05）。与空白对照组、溶剂对照组、1．00和2．50mg／kg染毒组比较，6．25mg／kg染毒组Bax蛋白表达水平明显升高，Bcl-2蛋白表达水平和Bcl-2／Bax比值明显下降，差异均有统计学意义（P〈0．05）。2．50和6．25mg／kg染毒组Caspase3、Caspase6蛋白表达水平明显高于空白对照组、溶剂对照组和1．0mg／kg染毒组，差异均有统计学意义（P〈0．05）。2．50和6．25mg／kg染毒组Caspase3、Caspase6和Caspase9蛋白活性明显高于空白对照和溶剂对照组，差异有统计学意义（P〈0．05）。大鼠海马组织Caspase3、Caspase6和Caspase9蛋白活性与细胞早期凋亡率呈正相关关系（r1=0．793，P=0．019．r2=0．886，P=-0．006；r

英文摘要：

Objective To observe the effectsof subchronic exposure to benzo[a]pyrene （B[alP） on the mRNA and protein expression levels of apoptosis-related genes （bax, bcl-2, caspase-3, caspase-6, and caspase- 9） and the activities of Caspase-3, Caspase-6, and Caspase-9 in the hippocampal neurons of rats and to investi- gate the neurotoxic mechanism by which B[a]P induces the apoptosis of neurons. Methods Fifty-two healthy SD rat were randomly divided into five groups according to preliminary neurobehavioral test results： blank con- trol group, solvent control group, and 1.0, 2.5, and 6.25 mg/kg B[a]P exposure groups; the rats in exposure groups were intraperitoneally injected with B[a]P every other day for 90 days. The Morris water maze was used to test the learning and memory ability of rats; flow cytometry was used to measure the apoptosis ratio of hip-pocampal neurons; real-time quantitative PCR and Western blot were used to measure the mRNA and protein expression levels of apoptosis-related genes; spectrophotometry was used to measure the activities of their en- coded proteins. Results Compared with the blank control group, solvent control group, and 1.0 mg/kg B[a]P exposure group, the 2.5 and 6.25 mg/kg B[a]P exposure groups had a significantly longer mean escape latency period （P〈0.05） and a significantly increased number of times of platform crossing （P〈O.05）, and the 6.25 mg/ kg B[a]P exposure group had significantly lower length and percentage of time spent in the platform quadrant （P〈0.05）. The early apoptosis ratio rose as the dose of B[a]P increased （P trend 〈0.05）; the early apoptosis ra- tios of 1.0, 2.5, and 6.25 mg/kg B[a]P exposure groups were significantly higher than those of blank control group and solvent control group （P〈O.05）. Compared with the blank control group, solvent control group, and 1.0 and 2.5 mg/kg B[a]P exposure groups, the 6.25 mg/kg B[a]P exposure group had significantly increased Bax expression （P 〈0.05） and significantly decreased Bcl-2 exp