从母系遗传研究肾阴虚型慢性再生障碍性贫血的发病机制

背景：多项研究表明恶性血液病可以出现线粒体的突变,但尚未有关于慢性再生障碍性贫血中线粒体变化的研究。目的：研究肾阴虚和肾阳虚型慢性再生障碍性贫血患者线粒体突变情况,探讨母系遗传的本质——线粒体与肾阴虚型慢性再障发生、发展的关系,以期进一步研究慢性再障的发病机制。方法：收集10例诊断明确的肾阴虚型5例肾阳虚型慢性再生障碍性贫血患者骨髓和口腔黏膜上皮,提取DNA,进行线粒体DNA的全测序,比较线粒体基因。结果与结论：肾阴虚型慢性再生障碍性贫血患者线粒体全测序表明许多患者的突变位点发生在与线粒体氧化呼吸链密切相关的区域,涵盖了还原态烟酰胺腺嘌呤二核苷酸脱氢酶1~2、4~6,细胞色素B等多个线粒体DNA的编码基因。而肾阳虚型慢性再生障碍性贫血患者线粒体突变不明显。提示线粒体基因突变引起的呼吸链酶复合体表达水平的改变,造成细胞能量代谢障碍,可能在造血干细胞衰竭的发生发展中起到关键作用。而这一变化是与肾阴虚——母系遗传息息相关的。

Pathogenesis of chronic aplastic anemia suffering from kidney yin deficiency through the maternal genetics

BACKGROUND： Several laboratories have reported unexpectedly large number of mitochondrial mutations in leukemia. But the direct relationship between mitochondrial mutations and chronic aplastic anemia （CAA） has not studied yet.OBJECTIVE： To study the mitochondrial mutations of CAA suffered from kidney yin deficiency and kidney yang deficiency, and to investigate the nature of maternal genetic： the relationship between mitochondrial and the occurrence and development of CAA suffered from kidney yin deficiency in order to further study the pathogenesis of CAA.METHODS： The bone marrow and the oral epithelium were obtained from 10 patients with CAA suffered from kidney yin deficiency and 5 patients with CAA suffered from kidney yang deficiency. DNA was extracted and underwent the entire sequencing of the mitochondrial DNA and compared the mitochondrial genome.RESULTS AND CONCLUSION： The entire sequencing of mitochondrial DNA in CAA suffer from kidney yin deficiency showed that the mutations were occurrence in the areas that closely related with mitochondrial oxidative respiratory chain, it included the reduced nicotinamide adenine dinucleotide dehydrogenase 1-2 and 4-6 and cytochrome B gene. However, the mitochondrial mutations in CAA suffered from kidney yang deficiency were not obvious. We are led to conclude that mitochondrial gene mutation can change the expression of respiratory chain enzyme complex in CAA patients, which results in energy metabolism impairment may participate in the physiological and pathology processes of hematopoietic failure. Functional impairment of mitochondrial respiration chain induced by gene mutation may be an important reason of hematopoietic failure in CAA. And this change is closely related to maternal inheritance and kidney yin deficiency.