慢性阻塞性肺疾病合并慢性缺氧患者肺动脉平滑肌细胞电压门控钾通道亚型基因表达的变化

Expression of voltage - gated potassium channel gene of pulmonary artery smooth muscle cells in COPD merge chronic hypoxic patients

目的:探讨人肺动脉平滑肌细胞(PASMCS)的几种KV通道亚型:KV1．2、KV1．3、KV1．5、KV2．1、KV3．1 等,在COPD合并慢性缺氧时基因表达的变化。旨在探索预防人类肺源性心脏病的发生和找到新的防治方法提供试验依据。方法:从手术室切取人正常肺组织、单纯COPD患者和COPD合并慢性缺氧患者肺组织,将标本分为:①正常对照的PASMCS、单纯COPD和COPD合并慢性缺氧患者的PASMCS;⑵正常对照的PASMCS和经过慢性缺氧培养的 PASMCS。利用半定量RT-PCR技术,分析,KV1．2、KV1．3、KV1．5、KV2．1、KV3．1等的基因表达。结果:①KV1．2、KV1．3、 KV1．5、KV2．1、KV3．1等基因在正常PASMCS和单纯COPD患者PASMCS中均有表达,而且两者无显著差异;②KV1．2、 KV1．5、KV2．1在患者在体慢性缺氧和离体慢性缺氧时的表达均明显降低(P<0．05);KV1．3在患者在体慢性缺氧时表达明显降低(P<0．05),而离体慢性缺氧时无显著变化(P>0．05);KV3．1在患者在体慢性缺氧和离体慢性缺氧时的表达均无显著变化(P>0．05);③KV1．2、KV1．5、KV2．1、KV3．1等基因在单纯COPD时表达显著上调(P<0．05)。结论: 在慢性缺氧情况下,KV1．2、KV1．3、KV1．5、KV2．1 4种亚型基因表达明显下降,提示可能在促进人肺动脉高压的形成和发展中起重要作用。而慢性缺氧对KV3．1基因表达无显著影响,提示它们可能对缺氧不敏感,在人肺动脉高压发生中处于次要地位。至于在单纯COPD时几种亚型的表达上调,原因不清楚,需进一步研究证实。

AIM： To study the change of expressions of Kv1. 2, Kv 1.3, Kv 1.5, Kv2.1, Kv3.1 genes in pulmonary artery, smooth muscle cells （PASMCs） on COPD merge chronic hypoxic patients. METHODS： Human lung tissue was collected from surgical patients. RT- PCR technique was used to study the expression of Kv1.2, Kv1.3, Kv1.5, Kv2.1 and Kv3.1 genes. PASMCs were divided into two groups： ① PASMCs from normal human pulmonary artery, pure COPD patients and COPD merger chronic hypoxic patients pulmonary ＇artery; ② Cultured PASMCs exposed to continual chronic hypoxia or normoxia. RESULTS：① The expression of Kv1.2, Kv1.3, Kv1.5, Kv2.1, Kv3.1 encoding genes were found in human PASMCs exposed to either nonnixa or chronic hypnxia.② The expression of Kv1.2, Kv1.5, Kv2.1 genes in PASMCs exposed to chronic hypoxia were significantly decreased compared with control groups （ P 〈 0.05）. ③ The expression of Kv1.3, Kv3.1 genes in PASMCs exposed to chronic hypoxia showed no significant change compared with control groups （ P 〉 0.05）. ① The expression of Kv1.2, Kv1.5, Kv2.1, Kv3.1 genes in pure COPD patients were significantly increased compared with control groups （ P 〈 0.05）. CONCLUSIONS： ①The resuits suggested that Kv1.2, Kv1.5, Kv2.1 genes may be oxygen sensitive gene. Their expressions are affected by chronic hypoxia, which probably play an important role in human pulmonary artery hypertension.② Kv1 .3, Kv3.1 genes may not be oxygen sensirive gene and their expression are not affected by chronic hypoxia, which might play a secondary role in human pulmonary artery hypertension.