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兩種芋螺毒素類似物抑制嗎啡誘導小鼠條件性位置偏愛及nNOS表達的研究

發(fā)布時間:2018-05-11 04:45

  本文選題:芋螺毒素類似物 + nNOS; 參考:《浙江大學》2012年碩士論文


【摘要】:1目的 在本實驗室前期研究基礎上,驗證[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、雄性小鼠中抗嗎啡精神依賴的藥效;觀察嗎啡成癮小鼠海馬腦區(qū)(Hp)神經(jīng)型一氧化氮合酶(neuronal nitric oxide synthase, nNOS)水平的變化,為進一步設計、篩選抗嗎啡依賴的芋螺毒素類似物提供理論和實驗依據(jù)。 2實驗方法 采用清潔級雄性與雌性昆明種小鼠,通過條件性位置偏愛裝置(conditioned place preference, CPP)檢測行為學改變,用Western blotting檢測目標蛋白變化。 3結果 CPP實驗結果顯示,側(cè)腦室分別給予120、240、480pmol Glu-Con-G和Glu-Con-G [1-13]對嗎啡誘導雄性小鼠CPP表達和復燃有抑制作用;側(cè)腦室給予Glu-Con-G [1-13]在120、480pmol劑量下對嗎啡誘導雌性小鼠CPP表達有抑制作用。 120、240、480pmol的Glu-Con-G和Glu-Con-G [1-13]均不影響小鼠的運動活性及探索行為。 Western blotting實驗結果顯示,120、240、480pmol的Glu-Con-G和Glu-Con-G[1-13]均可降低嗎啡成癮雄性小鼠海馬腦區(qū)nNOS蛋白含量,且成劑量相關性。 4結論 (1)單次側(cè)腦室內(nèi)分別給予120、240、480pmol Glu-Con-G可抑制嗎啡誘導雄性小鼠CPP的表達和復燃,但對雌性小鼠CPP表達的抑制作用不顯著; (2)單次側(cè)腦室內(nèi)分別給予120、240、480pmol Glu-Con-G [1-13]可抑制嗎啡誘導雄性小鼠CPP的表達和復燃,在120、480pmol劑量下對嗎啡誘導雌性小鼠CPP的表達也具抑制作用; (3)120、240、480pmol的Glu-Con-G和Glu-Con-G [1-13]均未顯著影響各階段對照小鼠和嗎啡成癮小鼠的運動活性和探索行為; (4)所給劑量的Glu-Con-G和Glu-Con-G [1-13]可抑制由長期嗎啡處理引起的雄性成癮小鼠海馬腦區(qū)nNOS蛋白表達水平的增加。
[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.

【學位授予單位】:浙江大學
【學位級別】:碩士
【學位授予年份】:2012
【分類號】:R749.6

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