两种芋螺毒素类似物抑制吗啡诱导小鼠条件性位置偏爱及nNOS表达的研究

发布时间：2018-05-11 04:45

本文选题：芋螺毒素类似物 + nNOS　；参考：《浙江大学》2012年硕士论文

【摘要】：1目的在本实验室前期研究基础上,验证[Glu3,4,7,10,14]-Conantokin-G (Glu-Con-G)及[Glu3,4,7,10,14]-Conantokin-G [1-13](Glu-Con-G [1-13])在雌、雄性小鼠中抗吗啡精神依赖的药效；观察吗啡成瘾小鼠海马脑区(Hp)神经型一氧化氮合酶(neuronal nitric oxide synthase, nNOS)水平的变化,为进一步设计、筛选抗吗啡依赖的芋螺毒素类似物提供理论和实验依据。 2实验方法采用清洁级雄性与雌性昆明种小鼠,通过条件性位置偏爱装置(conditioned place preference, CPP)检测行为学改变,用Western blotting检测目标蛋白变化。 3结果 CPP实验结果显示,侧脑室分别给予120、240、480pmol Glu-Con-G和Glu-Con-G [1-13]对吗啡诱导雄性小鼠CPP表达和复燃有抑制作用；侧脑室给予Glu-Con-G [1-13]在120、480pmol剂量下对吗啡诱导雌性小鼠CPP表达有抑制作用。 120、240、480pmol的Glu-Con-G和Glu-Con-G [1-13]均不影响小鼠的运动活性及探索行为。 Western blotting实验结果显示,120、240、480pmol的Glu-Con-G和Glu-Con-G[1-13]均可降低吗啡成瘾雄性小鼠海马脑区nNOS蛋白含量,且成剂量相关性。 4结论 (1)单次侧脑室内分别给予120、240、480pmol Glu-Con-G可抑制吗啡诱导雄性小鼠CPP的表达和复燃,但对雌性小鼠CPP表达的抑制作用不显著； (2)单次侧脑室内分别给予120、240、480pmol Glu-Con-G [1-13]可抑制吗啡诱导雄性小鼠CPP的表达和复燃,在120、480pmol剂量下对吗啡诱导雌性小鼠CPP的表达也具抑制作用； (3)120、240、480pmol的Glu-Con-G和Glu-Con-G [1-13]均未显著影响各阶段对照小鼠和吗啡成瘾小鼠的运动活性和探索行为； (4)所给剂量的Glu-Con-G和Glu-Con-G [1-13]可抑制由长期吗啡处理引起的雄性成瘾小鼠海马脑区nNOS蛋白表达水平的增加。
[Abstract]:1 purposes
On the basis of previous studies in our laboratory, the effects of [Glu3,4,7,10,14]-Conantokin-G (Glu-Con-G) and [Glu3,4,7,10,14]-Conantokin-G [1-13] (Glu-Con-G [1-13]) on the mental dependence of morphine in female and male mice were tested, and the Hp (neuronal nitric oxide synthase, nNO) was observed in the hippocampus of morphine addicted mice (neuronal nitric oxide synthase, nNO). The level of S) provides theoretical and experimental evidence for further design and screening of anti morphine dependent conoid toxin analogues.
2 experimental method
The behavior changes were detected by conditioned place preference (CPP), and the change of target protein was detected by Western blotting with clean grade male and female Kunming mice.
3 Results
The results of CPP experiment showed that 120240480pmol Glu-Con-G and Glu-Con-G [1-13] in the lateral ventricle inhibited the expression and reburning of CPP in the male mice induced by morphine, while the lateral ventricle gave Glu-Con-G [1-13] the inhibitory effect on the CPP expression induced by morphine induced female mice at the 120480pmol dose.
Glu-Con-G and Glu-Con-G [1-13] of 120240480pmol did not affect locomotor activity and exploratory behavior in mice.
The results of Western blotting experiment showed that both Glu-Con-G and Glu-Con-G[1-13] of 120240480pmol could reduce the content of nNOS protein in the hippocampus of morphine addicted male mice and have a dose-dependent manner.
4 Conclusion
(1) 120240480pmol Glu-Con-G in single lateral ventricle could inhibit the expression and reignition of CPP in male mice induced by morphine, but the inhibitory effect on CPP expression in female mice was not significant.
(2) 120240480pmol Glu-Con-G [1-13] in single lateral ventricle could inhibit the expression and reignition of CPP in male mice induced by morphine, and the expression of CPP in female mice induced by morphine also inhibited the expression of morphine at the dose of 120480pmol.
(3) Glu-Con-G and Glu-Con-G [1-13] of 120240480pmol did not significantly affect the locomotor activity and exploratory behavior of the control mice and morphine addicted mice at all stages.
(4) the doses of Glu-Con-G and Glu-Con-G [1-13] could inhibit the increase of nNOS protein expression in hippocampus of male addictive mice induced by long-term morphine treatment.

【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.6

【参考文献】