Department of Urology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
BJU Int. 2010 Mar;105(6):877-83. doi: 10.1111/j.1464-410X.2009.08809.x. Epub 2009 Aug 18.
To investigate differential gene expression profiles in the bladder of spontaneously hypertensive rat (SHR), as the underlying mechanisms involved in hypertension-associated bladder dysfunction remain to be clarified.
SHR and normotensive Wistar-Kyoto (WKY) rats were distributed initially in three groups: group 1 received doxazosin (30 mg/kg/day); group 2 received nifedipine (30 mg/kg/day); and group 3 received the vehicle orally for 4 weeks. The alterations in gene expression levels of candidate genes identified by microarray analysis with potential biological relevance were verified by real-time reverse transcription-polymerase chain reaction (RT-PCR).
Voiding frequency was significantly higher, and mean voided volume was significantly lower in untreated SHRs than untreated WKY rats. Microarray analysis revealed that 25 of the differentially expressed genes in untreated SHRs compared to untreated WKY rats were related to G(s), G(i), G(q) and G(12/13) signalling, calcium handling, ion transport and smooth muscle-related genes. Furthermore, RT-PCR data, in accord with the microarray analysis, indicated that untreated SHRs had lower mRNA expression levels of Adcy2, Adcy3, Rgs2, Rgs3, Rgs4 and Arhgdia, and higher mRNA expression levels of Arhgef1, Arhgef11, Arhgef12, Geft, Rock1 and Rock2 than untreated WKY rats. The differential alterations in the micturition patterns and in the expression of several genes related to G-protein signalling pathway observed in SHRs were attenuated by treatment with doxazosin, but not nifedipine.
Our data suggest that differential alterations in the expression of several genes related to G(s), G(q) and G(12/13) signalling pathways in the SHR bladder might be important in hypertension-associated bladder dysfunction.
研究自发性高血压大鼠（SHR）膀胱中的差异基因表达谱，因为高血压相关膀胱功能障碍的潜在机制仍需阐明。
将 SHR 和血压正常的 Wistar-Kyoto（WKY）大鼠最初分为三组：第 1 组给予多沙唑嗪（30mg/kg/天）；第 2 组给予硝苯地平（30mg/kg/天）；第 3 组给予口服载体 4 周。通过微阵列分析鉴定具有潜在生物学相关性的候选基因的表达水平变化，并用实时逆转录-聚合酶链反应（RT-PCR）进行验证。
未经治疗的 SHR 排尿频率明显高于未经治疗的 WKY 大鼠，平均排尿量明显低于未经治疗的 WKY 大鼠。微阵列分析显示，与未经治疗的 WKY 大鼠相比，未经治疗的 SHR 中 25 个差异表达基因与 G(s)、G(i)、G(q)和 G(12/13)信号转导、钙处理、离子转运和平滑肌相关基因有关。此外，与微阵列分析一致的 RT-PCR 数据表明，未经治疗的 SHR 的 Adcy2、Adcy3、Rgs2、Rgs3、Rgs4 和 Arhgdia 的 mRNA 表达水平较低，而 Arhgef1、Arhgef11、Arhgef12、Geft、Rock1 和 Rock2 的 mRNA 表达水平较高。与 G 蛋白信号通路相关的几个基因的表达在 SHR 中观察到的排尿模式的差异改变，经多沙唑嗪治疗后减弱，但硝苯地平治疗后未减弱。
我们的数据表明，SHR 膀胱中与 G(s)、G(q)和 G(12/13)信号通路相关的几个基因的表达差异改变可能在高血压相关膀胱功能障碍中很重要。
