不同证型H22肝癌小鼠肾上腺皮质类固醇激素合成酶及其调节因子表达的特征

Characteristics of Gene Expression of Adrenal Cortical Steroid Synthetase and Its Regulatory Factor in Mice with H22 Liver Cancer of Different Patterns

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中文关键词: 肾上腺皮质类固醇激素证型基因基因芯片肝癌

英文关键词:adrenal cortex steroid hormone pattern gene gene chip liver cancer

基金项目:上海市科委国际合作项目(No.064307052);国家科技重大专项课题资助项目(No.2009ZX09502-018)

作者	单位
吴中华	上海中医药大学基础医学院
潘志强	上海中医药大学基础医学院
卢文丽	上海中医药大学基础医学院
刘小美	上海中医药大学基础医学院
梁超	上海中医药大学基础医学院
管冬元	上海中医药大学基础医学院
高必峰	科罗拉多大学医学院
方肇勤	上海中医药大学基础医学院

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中文摘要:

目的观察不同证候肝癌小鼠肾上腺皮质类固醇激素合成酶及其调节因子的基因表达特征。方法采用小鼠计量化四诊和辨证方法筛选H22肝癌小鼠常见的邪毒壅盛证、气虚证、阳气虚证、气阴阳虚证,以GeneChip Mouse Exon1.0STArray(Affymetrix)等技术检测4个常见证候小鼠肾上腺组织基因表达谱,经过2批基因芯片重复验证后,重点分析肾上腺皮质激素合成酶及其调节因子的基因表达差异。结果两批基因芯片数据呈现良好的重复性,体现在高、低表达基因维持原表达状态。肾上腺皮质激素合成酶Cyp11a1、Star、Cyp11b2、Cyp21a1、Hsd3b、Hsd17b等基因表达量大,但证候间差异表达小。其中,Cyp11a1在4个证候均下调,Cyp11b2在4个证候均上调,Hsd3b1、Cyp21a1在邪毒壅盛证和气虚证下降,在阳气虚证和气阴阳虚证却上升。肾上腺皮质激素合成酶有关调节因子,在4个证候中Cyb5b、Wnt4一致下调,而Fdx1、Fdxr、Hsd11b1、Por、Agt、Nr0b1一致上调;Nr5a1在邪毒壅盛证下调,在3个虚证中却上调;Nr4a1、Nr4a2在邪毒壅盛证上调,在3个虚证中下调。结论肝癌小鼠肾上腺皮质激素合成酶基因比较保守与稳定,部分基因表达可能与疾病及其不同证候有关,体现了同病异证的差异。

英文摘要:

Objective To study the characteristics of gene expression of adrenal cortical steroid synthetase and its regulatory factor in mice with H22 liver cancer of different patterns. Methods Syndromes revealed in mice with H22 tumor were differentiated by quantified four diagnostic methods and syndrome differentiation,and mice with commonly encountered patterns (A:evil-toxin accumulation pattern,B:qi-defficiency pattern,C:yang-qi deficiency pattern and D:qi-yin-yang deficiency pattern) were screened out for subjecting to the study. Two batches of GeneChip Mouse Exon 1.0 ST Array detection were performed in the selected mice for detecting the gene expressions of adrenal cortical steroid synthetase and its regulatory factor,with the analysis performed put stress on the differential expressions in mice of various syndrome patterns. Results Data obtained from the two batches detection showed well repeatability,in which similar genes of high or low expression emerged. The adrenal cortical steroid synthetase genes,such as Cyp11a1,Star,Cyp11b2,Cyp21a1,Hsd3b and Hsd17b were highly expressed,with few difference among the four patterns. However,Cyp11a1 was down-regulated and Cyp11b2 up-regulated in all patterns; Hsd3b1 and Cyp21a1 down-regulated in pattern A and B,but up-regulated in pattern C and D. As for the expressions of the relative regulatory factors,Cyb5b and Wnt4 were down-regulated but Fdx1,Fdxr,Hsd11b1,Por,Agt and Nr 0b1 were up-regulated in all patterns; Nr5a1 down-regulated in pattern A but up-regulated in other three patterns; Nr4a1 and Nr4a2 up-regulated in pattern A and down-regulated in the others. Conclusions The adrenal cortical steroid synthetase genes are rather conservative and stable in mice bearing H22 liver cancer,part of the expression might be correlated to the condition of disease and essence of syndromes,embodying the differences among different patterns in the same disease.

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