【摘要】 目的:研究硒代蛋氨酸（Se-Met）对铅暴露大鼠脑组织损伤的保护作用,并探讨其作用机制。方法:50只健康雄性Wistar大鼠随机分正常对照组、铅损伤模型组（Pb组）,Pb+低、中和高剂量Se-Met （Pb+L Se-Met、Pb+M Se-Met和Pb+H Se-Met）组（n=10）。除正常对照组外,其余4组大鼠自由饮用浓度为1 g·L^-1(546.2 mg·L^-1Pb)的醋酸铅溶液,共4周,建立铅损伤模型。Pb+L Se-Met、Pb+M Se-Met和Pb+H Se-Met组大鼠每天给予0.1、0.2和0.4 g·kg^-1Se-Met,以5 mL蒸馏水混悬液灌胃给药,正常对照组和Pb组大鼠每天给予等体积蒸馏水灌胃,连续6周。采用石墨炉原子吸收光谱法测定各组大鼠骨铅含量;Morris水迷宫实验检测大鼠行为学指标;生化法检测大鼠脑组织中谷胱甘肽过氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）、胆碱酯酶（CHE）活性和丙二醛（MDA）及一氧化氮（NO）水平;HE染色观察各组大鼠脑海马CA1区病理形态表现;免疫组织化学法观察各组大鼠脑海马CA1区细胞凋亡蛋白[B细胞淋巴瘤2 （Bcl-2）、Bcl-2相关X蛋白（Bax）]和硒蛋白S （SelS）的表达。结果:与正常对照组比较,Pb组、Pb+L Se-Met组、Pb+M Se-Met组和Pb+H Se-Met组大鼠骨铅含量明显增加（P<0.01）;Morris水迷宫实验中大鼠逃避潜伏期明显延长（P<0.01）,总运动距离明显增加（P<0.01）,目标象限滞留时间明显缩短（P<0.05）,穿越次数明显降低（P<0.05）;大鼠脑组织中GSH-Px、 SOD和CHE活性明显降低（P<0.01）,MDA和NO水平明显升高（P<0.01）。与正常对照组比较,Pb组大鼠海马CA1区神经细胞排列不整齐,细胞形态不规则呈多角形,细胞核浓缩深染。与Pb组比较,Pb+L Se-Met组、Pb+M Se-Met组和Pb+H Se-Met组大鼠骨铅含量明显降低（P<0.01）;Morris水迷宫试验中大鼠逃避潜伏期明显缩短（P<0.01）,总运动距离明显缩短（P<0.01）,目标象限滞留时间明显延长（P<0.05）,穿越次数明显增加（P<0.05）;大鼠脑组织中GSH-Px、SOD和CHE活性升高（P<0.01）,MDA和NO水平明显降低（P<0.01）;大鼠海马CA1区病理改变减轻;SelS和Bcl-2蛋白表达量增加,Bax蛋白表达量降低。结论:Se-Met对铅暴露大鼠脑组织损伤具有一定保护作用,其作用机制与降低铅暴露大鼠体内铅负荷、减少氧化损伤和脑海马CA1区细胞凋亡、增加大鼠脑海马CA1区SelS表达有关。更多还原

【Abstract】 Objective:To study the protective effect of selenomethionine（Se-Met）on the brain tissue damage in the rats exposed to lead,and to explore its mechanism. Methods:Fifty healthy male Wistar rats were randomly divided into normal control group,Pb injury model group（Pb group）,Pb+low,medium and high doses of Se-Met groups（Pb+L Se-Met group,Pb+M Se-Met group,Pb+H Se-Met group）（n=10）. In addition to normal control group,the rats in other 4 groups were fred to drink lead acetate solution with a concentration of 1 g·L^-1(546. 2 mg·L^-1 Pb)to establish the lead-damaged rat models.After 4 weeks the rats in low,medium,and high doses of Pb+Se-Met groups received 0. 1,0. 2 and 0. 4 g·kg^-1 Se-Met and administrated with 5 mL distilled water suspension by gavage every day;the rats in normal control group and Pb group were given equal volume of distilled water every day for 6 weeks.After 6 weeks,the bone lead content of the rat was measured by graphite furnace atomic absorption spectrometry;Morris water maze experiment was carried out to detect the behavior indexes of the rats. The activities of glutathione peroxidase（GSH-Px）,superoxide dismutase（SOD）and cholinesterase（CHE）and the levels of malondialdehyde（MDA）and nitric oxide（NO）in brain tissue of the rats were detected by chemical colorimetry. HE staining was used to observe the patholmorphology of the rat hippocampus CA1 region. Immunohistochemistry was used to observe the expressions of B-cell lymphoma2（Bcl-2）,Bcl-2 associated X protein（Bax）,and selenoprotein S（Sel S） in the rat hippocampus CA1 region in various groups. Results:Compared with normal control group,the bone lead contents of the rats in Pb group,Pb+L Se-Met group,Pb+M Se-Met group and Pb+H Se-Met group were significantly increased（P<0. 01）,the escape latencies and the movement distance of the rats in Morris water maze experiment rats were significantly increased（P<0. 01）,the residence time in target quadrant and the across times were significantly reduced（P<0. 05）,the activities of GSH-Px,SOD and CHE in brain tissue of the rats were significantly decreased（P<0. 01）,and the levels of MDA and NO were significantly increased（P<0. 01）.Compared with normal control group,the nerve cells in hippocampal CA1 region of the rats in Pb group didn’t arrange neatly,the morphology of cells was irregular,presenting polygon,and the nuclei were concentrated and hyperchromatic. Compared with Pb group,the bone lead contents of the rats in Pb+L SeMet group,Pb+M Se-Met group and Pb+H Se-Met group were significantly reduced（P<0. 01）,the escape latencies and the movement distance of the rats in Morris water maze experiment were significantly reduced（P<0. 01）,the residence time in taget quadrant and the across times were significantly increased（P<0. 05）,the activities of GSH-Px,SOD and CHE were increased（P<0. 01）,and the levels of MDA and NO were significantly reduced（P<0. 01）;the pathological changes in hippocampal CA1 region of the rats were improved,the expression amounts of SelS and Bcl-2 proteins were increased,and the Bax protein expression amounts were reduced. Conclusion:Se-Met has a protective effect on the brain tissue damage of the rats exposed to lead,and its mechanism may be related to reducing the lead load in the body of the rats exposed to lead,reducing oxidative damage,apoptosis in hippocampus CA1 region of brain,and increasing the expression of SelS in CA1 region in hippocampus of the rats.更多还原