机构地区:[1]山西医科大学公共卫生学院劳动卫生教研室,山西太原030001
出 处:《中国职业医学》2020年第1期24-29,共6页China Occupational Medicine
基 金:国家自然科学基金(81430078,81703202);太钢科研基金(201808)。
摘 要:目的观察麦芽酚铝对大鼠海马区突触可塑性的影响,探讨代谢型谷氨酸受体1(mGluR1)在其中的调节作用及机制。方法取无特定病原体级健康成年雄性SD大鼠随机分为对照组、染铝组、铝激动剂组和铝拮抗剂组,每组8只。对照组大鼠不予任何处理;采用侧脑室染毒法,染铝组大鼠予5μL浓度为10 mmol/L麦芽酚铝溶液,铝激动剂组和铝拮抗剂组大鼠在予3μL浓度为10 mmol/L的麦芽酚铝溶液的同时,分别予2μL浓度为0.1μmol/L mGluR1激动剂或0.2μmol/L mGluR1拮抗剂,每2天染毒1次,共5次,持续染毒10 d。染毒结束后,测定各组大鼠海马CA1区长时程增强(LTP)幅值;采用实时荧光定量聚合酶链式反应法和免疫印迹法分别检测各组大鼠海马组织mGluR1、N-甲基-D-天冬氨酸受体(NMDAR1)、蛋白激酶C(PKC)的mRNA和蛋白相对表达水平。结果染铝组和铝激动剂组大鼠海马CA1区LTP幅值均低于对照组和铝拮抗剂组(P<0.05)。与对照组比较,染铝组大鼠海马组织mGluR1的mRNA与蛋白相对表达水平均升高(P<0.05),NMDAR1和PKC的mRNA与蛋白相对表达水平均下降(P<0.05)。与染铝组比较,铝激动剂组大鼠海马组织mGluR1的mRNA与蛋白相对表达水平均升高(P<0.05),NMDAR1 mRNA相对表达水平下降(P<0.05);铝拮抗剂组大鼠海马组织mGluR1的mRNA与蛋白相对表达水平均下降(P<0.05),NMDAR1的mRNA与蛋白相对表达水平均升高(P<0.05);与铝激动剂组比较,铝拮抗剂组大鼠海马组织mGluR1的mRNA与蛋白相对表达水平均下降(P<0.05),NMDAR1的mRNA与蛋白相对表达水平均升高(P<0.05)。铝激动剂组和铝拮抗剂组大鼠海马组织PKC的mRNA与蛋白相对表达水平比较,以及分别与对照组、染铝组比较,差异均无统计学意义(P>0.05)。结论麦芽酚铝染毒可通过抑制大鼠海马区LTP而抑制突触可塑性;其机制可能与mGluR1对NMDAR1表达的调节有关。Objective To observe the effect of maltolate aluminum on synaptic plasticity in the hippocampus of rats and to explore the regulatory effect and mechanism of metabotropic glutamate receptor 1(mGluR1).Methods Specific pathogen free healthy adult male SD rats were randomly divided into control group,aluminum group,aluminum agonist group and aluminum antagonist group,8 rats in each group.The rats in the control group received no treatment;the rats in aluminum group were injected with 5μL 10 mmol/L maltolate aluminum solution into the lateral ventricle;the rats in aluminum agonists and aluminum antagonist group were injected with 3μL 10 mmol/L maltolate aluminum solution plus 2μL 0.1μmol/L mGluR1 agonist or 2μL 0.2μmol/L mGluR1 antagonists into the lateral ventricle,respectively.Maltolate aluminum solution was injected every 2 days and continued for 10 days.After maltolate aluminum exposure,the amplitudes of long-term potentiation(LTP)in hippocampal CA1 region of rats were measured,and the relative expression levels of mRNA and protein of mGluR1,N-methyl-D-aspartate receptor(NMDAR1)and protein kinase C(PKC)in hippocampus tissue of rats were detected by real-time fluorescence quantitative polymerase chain reaction and Western blotting.Results The amplitude of LTP in hippocampal CA1 region in aluminum group and aluminum agonist group was lower than that in the control group and the aluminum antagonist group(P<0.05).Compared with the control group,the relative expression of mGluR1 mRNA and protein in the aluminum group increased,the relative expression of PKC and NMDAR1 mRNA and protein in the aluminum group decreased(P<0.05).Compared with the aluminum group,the relative expression of mGluR1 mRNA and protein in the aluminum agonist group increased,while the NMDAR1 mRNA decreased(P<0.05);the relative expression of mGluR1 mRNA and protein in the aluminum antagonist group decreased,while the NMDAR1 mRNA and protein increased(P<0.05).Compared with the aluminum agonist group,the relative expression of mGluR1 mRNA and p
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