SRC-1、NCOR在不同脑区的表达及淫羊藿、女贞子对其表达的影响
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摘要
SRC-1(steroid receptor coactivator-1)和NCOR(nuclear receptor corepressor)属于核受体共调节因子超家族的成员,在中枢神经系统中有广泛的表达,能通过和相应的核受体相互作用而调节靶基因的表达。补肾中药中多种药物具有类似于雌激素的生物效应,如,淫羊藿、女贞子等,在治疗多种与脑退行性病变有关的疾病中有较多的应用。为探讨SRC-1和NCOR在大脑不同区域的表达,及补肾中药淫羊藿、女贞子是否通过影响SRC-1和NCOR mRNA的表达而发挥作用,特设计本课题。因此,本研究以雌激素类药物倍美力和雌激素拮抗药物氯米芬为药物对照,蒸馏水为空白对照,通过对淫羊藿含药血清、女贞子含药血清对乳腺癌细胞MCF-7和雌激素受体缺失的乳腺癌细胞MDA-MB-231的SRC-1、NCOR两个基因mRNA表达量影响的体外实验和SRC-1、NCOR mRNA在不同脑区的表达及淫羊藿对其表达的影响的在体实验分析,探讨淫羊藿、女贞子临床作用可能的药理机制,为其临床应用提供依据。
主要结论:
1本实验所用药品淫羊藿、女贞子都符合中国药典2005版质量控制标准的要求。
2雌雄性大鼠的海马、杏仁核和大脑皮质及雌性大鼠的下丘脑中,SRC-1和NCOR mRNA都有表达,且表达量不同。
3淫羊藿上调了下丘脑、海马、杏仁核和大脑皮质中SRC-1和NCOR mRNA的表达,且在下丘脑中对SRC-1和NCOR mRNA表达的上调效果明显。
女贞子上调了杏仁核和大脑皮质中SRC-1和NCOR mRNA表达。
4淫羊藿、女贞子对雌激素受体阳性细胞和雌激素受体阴性细胞的SRC-1和NCOR mRNA的表达有明显不同的影响。
SRC-1 and NCOR are the members of nuclear receptor coregulators superfamily, andhave wide expressions in the central nervous system .They can regulate the expression of targetgene through interaction with the proper nuclear receptors. Many Chinese nourishing kidneyherbs have the effect of estrogen, and were cured variety brain-related diseases. We design theissue to study the mRNA expression of steroid hormone receptor coactivator-1 and nuclearreceptor corepressor in different brain domain and to investigate whether Icariin epimedii andLigustrum lucidum play roles by affecting expression of steroid hormone receptor coactivator-1and nuclear receptor corepressor. Therefore, we regard estrogen drugs Premarin and the estrogenantagonist clomiphene as drug control, distilled water as blank control, explore the possiblepharmacological mechanism for the clinical application of Icariin epimedii and Ligustrumlucidum through analyzing the vitro experiment that we study the effect of drug serum containedIcariin epimedii or Ligustrum lucidum for the mRNA expression of steroid hormone receptorcoactivator-1 and nuclear receptor corepressor in breast cancer cells MCF-7 and MDA-MB-231(estrogen receptor deficiency),and the vivo experiment that The expression of SRC-1, NCOR indifferent brain domain and the effect for the expression of herba epimedii,gustrum lucidum .Wehope that our study can provide the basis for the clinical application of Chinese medicine .
The main conclusions:
1 Icariin epimedii and Ligustrum lucidum used in this experiment measure up to the quality control standards of the Chinese Pharmacopoeia 2005 edition.
2 There are different expression of SRC-1 and NCOR mRNA in the different brain domain of male and female rats.
3 Icariin epimedii up-regulates the expression of SRC-1 and NCOR mRNA in hypothalamus, hippocampus, amygdala and cerebral cortex, and the up-regulation is more significantly in hypothalamus.
Ligustrum lucidum up-regulates the expression of SRC-1 and NCOR mRNA in amygdala and cerebral cortex.
4 In the cells of ER-positive and ER-negative, Icariin epimedii and Ligustrum lucidum have different effects for the expression of SRC-1 and NCOR mRNA.
主要结论:
1本实验所用药品淫羊藿、女贞子都符合中国药典2005版质量控制标准的要求。
2雌雄性大鼠的海马、杏仁核和大脑皮质及雌性大鼠的下丘脑中,SRC-1和NCOR mRNA都有表达,且表达量不同。
3淫羊藿上调了下丘脑、海马、杏仁核和大脑皮质中SRC-1和NCOR mRNA的表达,且在下丘脑中对SRC-1和NCOR mRNA表达的上调效果明显。
女贞子上调了杏仁核和大脑皮质中SRC-1和NCOR mRNA表达。
4淫羊藿、女贞子对雌激素受体阳性细胞和雌激素受体阴性细胞的SRC-1和NCOR mRNA的表达有明显不同的影响。
SRC-1 and NCOR are the members of nuclear receptor coregulators superfamily, andhave wide expressions in the central nervous system .They can regulate the expression of targetgene through interaction with the proper nuclear receptors. Many Chinese nourishing kidneyherbs have the effect of estrogen, and were cured variety brain-related diseases. We design theissue to study the mRNA expression of steroid hormone receptor coactivator-1 and nuclearreceptor corepressor in different brain domain and to investigate whether Icariin epimedii andLigustrum lucidum play roles by affecting expression of steroid hormone receptor coactivator-1and nuclear receptor corepressor. Therefore, we regard estrogen drugs Premarin and the estrogenantagonist clomiphene as drug control, distilled water as blank control, explore the possiblepharmacological mechanism for the clinical application of Icariin epimedii and Ligustrumlucidum through analyzing the vitro experiment that we study the effect of drug serum containedIcariin epimedii or Ligustrum lucidum for the mRNA expression of steroid hormone receptorcoactivator-1 and nuclear receptor corepressor in breast cancer cells MCF-7 and MDA-MB-231(estrogen receptor deficiency),and the vivo experiment that The expression of SRC-1, NCOR indifferent brain domain and the effect for the expression of herba epimedii,gustrum lucidum .Wehope that our study can provide the basis for the clinical application of Chinese medicine .
The main conclusions:
1 Icariin epimedii and Ligustrum lucidum used in this experiment measure up to the quality control standards of the Chinese Pharmacopoeia 2005 edition.
2 There are different expression of SRC-1 and NCOR mRNA in the different brain domain of male and female rats.
3 Icariin epimedii up-regulates the expression of SRC-1 and NCOR mRNA in hypothalamus, hippocampus, amygdala and cerebral cortex, and the up-regulation is more significantly in hypothalamus.
Ligustrum lucidum up-regulates the expression of SRC-1 and NCOR mRNA in amygdala and cerebral cortex.
4 In the cells of ER-positive and ER-negative, Icariin epimedii and Ligustrum lucidum have different effects for the expression of SRC-1 and NCOR mRNA.
引文
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[18] Loinder K, Soderstrom M. Functional analyses of an LXXLL motif in nuclear receptor corepressor (NCoR). Steroid Biochem Mol Biol, 2004,91(4-5): 191-196.
[19] Leong GM, Subramaniam N, Issa L, et al. Skiinteracting protein, a bifunctional nuclear receptor coregulator that interacts with NCoR/SMRT and p300. Biochem Biophys Res Commun, 2004,315(4):1070-1076.
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