头顶一颗珠对衰老大鼠认知及海马BDNF、TrkB的影响

Effect of Extracts from Trilliumtschonoskii Maxim on Cognitive Ability and Expression of BDNF and TrkB in Hippocampus of Rats with Aging

目的探讨头顶一颗珠提取物(TTM)对衰老大鼠认知能力及海马组织中脑源性神经营养因子(BDNF)和酪氨酸激酶B(TrkB)表达的影响。方法将雄性SD大鼠30只随机分为3组:对照组、模型组、TTM组,每组10只。模型和TTM组皮下注射100 mg/kg D-半乳糖,对照组注射等量生理盐水;同时,TTM组用100 mg/kg TTM灌胃,对照组和模型组灌胃等量生理盐水,每日1次,连续给药6周。Morris水迷宫训练并测试大鼠认知能力,取大鼠海马组织测超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,HE染色观察形态学改变,免疫荧光染色检测神经元损伤,Western Blot检测海马组织内BDNF和TrkB蛋白表达。结果与对照组比较,模型组大鼠认知功能下降,海马组织内SOD活性下降(P<0.01),MDA含量升高(P<0.01),8-OHDG阳性表达增多,BDNF、TrkB及p-TrkB蛋白水平均降低(P<0.01)。与模型组比较,TTM干预后大鼠认知功能改善,海马组织内SOD活性增加(P<0.05),MDA含量降低(P<0.01),BDNF、TrkB及p-TrkB水平均提高(P<0.01,P<0.05)。结论TTM可改善衰老大鼠认知功能障碍,可能与提高海马组织内BDNF和TrkB表达、增强抗氧化能力有关。

Objective To explore the effect of extracts from Trilliumtschonoskii Maxim(TTM)on the cognitive ability of rats with aging and the expression of brain-derived haurotrophic factor(BDNF)and tyrosine kinase receptor BC(TrkB)in hippocampus.Methods Thirty male SD rats were randomly divided into three groups,i.e.,the control group,the model group and the TTM group,with 10 rats in each group.Rats in the model group and TTM group were administrated with 100 mg/kg of D-galactose(D-gal)subcutaneously in the neck and back every day,and with the equal amount of normal saline(NS)in the control group.Rats in the TTM group were administered intragastrically with 100 mg/kg of TTM once a day,while the control group and the model group received equal volume of normal saline for 6 weeks.The cognitive ability of rats was tested by Morris water maze.Morphological changes of hippocampus were detected by HE staining.The DNA damage in hippocampus was evaluated using immunofluorescence staining.The malondialdehyde(MDA)content in hippocampus was determined by Thiobarbituric acid method and superoxide dismutose(SOD)activity using xanthine oxidase method.The expression of BDNF and TrkB was tested by Western Blot analysis.Results Compared with the control group,the ability of learning and memory impaired,the SOD activity decreased(P<0.01)and MDA content increased(P<0.01),the positive expression of 8-hydroxy-2-deoxyguanosine(8-OHDG)elevated,and the levels of BDNF,TrkB and p-TrkB in hippocampus tissues in the model group significantly decreased(P<0.01).Compared with the model group,the cognitive ability improved in the TTM group,SOD activity increased(P<0.05),and MDA content decreased(P<0.01).Moreover,the levels of BDNF,TrkB and p-TrkB in the TTM group significantly elevated(P<0.01,P<0.05)compared with those in the model group.Conclusion TTM could significantly improve the learning and memory dysfunction of rats with aging caused by D-gal,which might be related to the increase of the expression of BDNF and TrkB proteins in the hippocampus and the enhancement of antioxidative ability.