慢性间歇低氧上调心肌lncRNA MALAT1及相关分子的表达

The long non-coding RNA MALAT1 is upregulated in myocardial tissue exposed to intermittent hypoxia

目的通过观察长链非编码RNA(lnc RNA)中转移相关肺腺癌转录本1(MALAT1)及其相关的炎症因子在不同低氧处理后心肌组织中的表达,探讨MALAT1在阻塞性睡眠呼吸暂停(OSA)导致心血管并发症中可能的作用机制。方法将成年SD大鼠随机分为持续低氧组(CH组)、间歇低氧组(IH组)、间歇低氧伴高二氧化碳组(IHH组)并进行相应低氧处理,设置正常对照组(N组),每组8只。上述处理分别进行1周、2周、3周后处死大鼠,提取大鼠心肌组织RNA样本,采用q RT-PCR法检测MALAT1基因的表达。结果干预1周时低氧处理的各组MALAT1基因表达较对照组有升高趋势,但差异无统计学意义。2周和3周时,IHH组大鼠心肌MALAT1基因的表达量较IH组、CH组和N组均显著升高(均P<0.01);IH组、CH组大鼠MALAT1基因的表达量较N组有升高趋势,但差异无统计学意义。低氧处理3周IHH组缺氧诱导因子-1α、Toll样受体4、白细胞介素-6的m RNA表达量均较其他三组显著升高,与MALAT1的变化趋势一致。结论心肌MALAT1在低氧伴高二氧化碳处理后表达升高,与相关的重要缺氧及炎症因子上调趋势一致,提示MALAT1可能是OSA心肌免疫损伤的调控因子。

Objective By detecting the expression of the long non-coding RNA metastasis associated lung adenocarcinoma transcript 1（MALAT1） in myocardial tissue under different hypoxia patterns, to explore the possible mechanism of obstructive sleep apnea（OSA）-induced cardiovascular diseases. Methods SD rats were randomly and equally divided into 4 groups namely a normal（N） group, a continuous hypoxia（CH） group, an intermittent hypoxia（IH）group and an intermittent hypoxia with hypercapnia（IHH） group, and were treated for 1, 2, and 3 weeks. The expression of MALAT1 and associated immune factors of the myocardial tissue were examined by q RT-PCR. Results An elevation without significance was observed in those three hypoxia groups in contrast with N group after 1 week＇s treatment.However, in 2 and 3 weeks＇ groups, the m RNA expression of MALAT1 was significantly higher in IHH group than the other three groups（all P〈0.01）, while there was no significant difference among IH, CH or N groups despite an increasing tendency in IH and CH groups against N group were observed. Additionally, the expressions of hypoxia inducible factor-1α（P〈0.05）, Toll-like receptor 4（P〈0.01） and interleukin-6（P〈0.05） m RNA were also increased significantly in IHH group compared with IH, CH and IHH groups in 3 weeks＇ treatment respectively, which were coordinated with the change of MALAT1 m RNA. Conclusions The expression of MALAT1 in myocardial tissue is elevated by intermittent hypoxia with hypercapnia, and the tendency is similar with hypoxia-induced inflammation factors. These findings indicate that MALAT1 is probably a regulatory factor of OSA induced myocardial immune injury.