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野百合碱诱导的大鼠右心室肥厚中Kv4.2和Kv4.3通道基因表达下调

Downregulation of Kv4.2 and Kv4.3 channel gene expression in right ventricular hypertrophy induced by monocrotaline in rat.

作者信息

Zhang Tian-tai, Cui Bing, Dai De-zai

机构信息

Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.

出版信息

Acta Pharmacol Sin. 2004 Feb;25(2):226-30.

PMID:14769214
Abstract

AIM

To investigate the differences in gene expression of transient outward potassium ion channel between the free wall of right ventricle, free wall of left ventricle, and the septum in monocrotaline (MCT)-induced right ventricular hypertrophy of rat.

METHODS

Twenty rats were randomly divided into two groups: a single injection of monocrotaline (MCT) 60 mg/kg (model) or saline (control). Four weeks later, hemodynamic parameters were measured and the gene expression of Ito channels were detected by semi-quantitative RT-PCR.

RESULTS

After 28 d, the right ventricular systolic pressure and central venous pressure were remarkably elevated by 128% and 533% in the MCT-treated group, accompanied by an overt right ventricle (RV) remodeling. The difference of mRNA expression of Kv1.4 was not significant in free wall of RV, left ventricle (LV), and septum in MCT group compared with control group. In contrast, mRNA of Kv4.2 and Kv4.3 in the free wall of RV in MCT-induced rat was dramatically decreased by 45.2% and 51.1% vs control, however, in free wall of LV and septum, no difference was found. In addition, mRNA expression level of Kv4.2 in control rat was significantly lower in septum than that in free wall of RV and LV.

CONCLUSION

Expression of Kv1.4, Kv4.2, and Kv4.3 differs between regions in normal rat hearts. The down-regulation of Kv4 family gene expression of Ito contributed to the pathophysiological changes in ventricular hypertrophy and pulmonary hypertension induced by MCT.

摘要

目的

研究在野百合碱(MCT)诱导的大鼠右心室肥厚模型中,右心室游离壁、左心室游离壁和室间隔之间瞬时外向钾离子通道基因表达的差异。

方法

将20只大鼠随机分为两组:单次注射60mg/kg野百合碱(MCT)(模型组)或生理盐水(对照组)。四周后,测量血流动力学参数,并通过半定量逆转录聚合酶链反应(RT-PCR)检测Ito通道的基因表达。

结果

28天后,MCT处理组的右心室收缩压和中心静脉压显著升高,分别升高了128%和533%,同时伴有明显的右心室(RV)重塑。与对照组相比,MCT组右心室游离壁、左心室(LV)和室间隔中Kv1.4的mRNA表达差异不显著。相反,MCT诱导的大鼠右心室游离壁中Kv4.2和Kv4.3的mRNA与对照组相比显著降低,分别降低了45.2%和51.1%,然而,在左心室游离壁和室间隔中未发现差异。此外,对照组大鼠中Kv4.2的mRNA表达水平在室间隔中显著低于右心室和左心室游离壁。

结论

正常大鼠心脏中不同区域Kv1.4、Kv4.2和Kv4.3的表达存在差异。Ito的Kv4家族基因表达下调促成了MCT诱导的心室肥厚和肺动脉高压的病理生理变化。

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