大黄酚对铅中毒小鼠学习记忆的改善作用及其机制研究

目的研究大黄酚对铅中毒小鼠学习记忆障碍的改善作用,探讨其可能的作用机制。方法采用连续8 d腹腔注射7 mg.kg-1醋酸铅造成铅中毒小鼠模型,应用避暗实验、水迷宫实验,观察腹腔注射大黄酚(10.0、1.0、0.1 mg.kg-1)14 d对铅中毒模型小鼠记忆障碍的改善作用,大黄酚治疗14 d后测定小鼠血铅、脑铅及脑组织中MDA含量SOD,GSH-Px活力,一氧化氮(NO)含量及一氧化氮合酶(NOS)、诱导型一氧化氮合酶(iNOS)的活性。结果连续8 d腹腔注射7 mg.kg-1醋酸铅造成铅中毒小鼠学习记忆障碍,使小鼠脑铅、血铅升高,导致小鼠脑组织内SOD和GSH-Px活性降低,使小鼠脑组织内MDA含量增加,小鼠脑组织内NO含量增加,NOS和iNOS活性升高;连续ip大黄酚14d治疗后,可不同程度改善小鼠铅中毒造成的学习记忆障碍,降低血铅及脑铅水平,大黄酚(0.1 mg.kg-1)可升高铅中毒小鼠脑内SOD和GSH-Px的活性(P<0.01),对MDA含量无影响;大黄酚(10.0、1.0 mg.kg-1)可升高铅中毒小鼠脑内SOD和GSH-Px的活性,降低小鼠脑内MDA含量(P<0.01);大黄酚(0.1 mg.kg-1)可降低小鼠脑内NOS、iNOS的活性(P<0.05),对NO含量无影响;大黄酚10.0,1.0 mg.kg-1治疗组可降低小鼠脑内NO含量和NOS、iNOS的活性(P<0.01)。结论大黄酚通过提高铅中毒小鼠脑组织抗氧化酶活性同时降低NOS、iNOS的活性,抑制脂质过氧化,明显拮抗铅诱导的小鼠学习记忆障碍。

Effects of chrysophanol on learning and memory impairment induced by lead in mice and the study of its mechanisms

Aim To investigate the effects of chrysophanol(Chry) on memory impairment in mice induced by lead acetate and discuss its possible mechanisms.Methods Mice,except control group were administered 7 mg·kg-1lead acetate by peritoneal injection every day for 8 days to establish the lead poisoning model.Chry was ip injected for 14 days.The abilities of learning and memory were examined by step through test and Morris water maze test.Antioxidant enzyme levels(GSH-Px,SOD) and lipid peroxidation products(MDA) were performed by UV spectrophotometry scenery.The contents of nitrogen monoxidum(NO),nitricoxide synthase(NOS) in brain tissue were examined.Results Lead acetate could induce the disorder of space learning and memory,and it could also increase the lead levels of mouse blood and brain,the content of NO and MDA,and the activities of NOS and iNOS of brain.Additionally,lead acetate could decrease the activities of SOD and GSH-Px of mouse brain.Chry could improve the learning and memory impairment and decrease the lead levels in blood and brain.Chry(0.1 mg·kg-1) could decrease the activities of NOS and iNOS in mouse brain(P<0.05),There was no significant influence on content of NO,while Chry(10.0,1.0 mg·kg-1) could decrease the content of NO and the activities of NOS and iNOS in mouse brain(P<0.01).Chry(0.1 mg·kg-1) could increase the activities of SOD and GSH-Px in mice brain(P<0.01).There was no significant effect on content of MDA,while Chry(10.0,1.0 mg·kg-1) could decrease the content of MDA and increase the activities of SOD and GSH-Px in mice brain(P<0.01).Conclusion Chry can significantly improve the impairment of learning and memory and antioxidant defense system of mice induced by lead acetate,and apparently inhibit lipid peroxidation.