1型糖尿病大鼠左心室HCN2和HCN4重构
The expression of HCN2 and HCN4 in the left ventricle of type 1 diabetes rat
目的 探讨1型糖尿病大鼠左心室肌HCN2和HCN4的表达时空变化。 方法 60只大鼠随机分为正常对照组(N组, n=20)和1型糖尿病组(T1DM组, n=40):腹腔注射链脲佐菌素制作大鼠1型糖尿病模型。90 d后,取左心室肌通过免疫荧光法检测HCN2、HCN4的定位;Western-blot、RT-PCR技术检测HCN2、HCN4在蛋白质及mRNA水平的变化。 结果 免疫荧光结果显示HCN2在心室肌细胞膜上呈点状或短线状不连续表达;HCN4未见表达。Western-blot、RT-PCR结果显示T1DM组大鼠 HCN2、HCN4在蛋白及mRNA水平表达升高。 结论 1型糖尿病大鼠左心室出现离子通道HCN2、HCN4表达升高,导致糖尿病心脏电重构,可能与糖尿病引起的室性心律失常有关。
Objective To investigate the expression of HCN2 and HCN4 in the left ventricles of type 1 diabetes rat. Methods 60 rats were randomly divided into control group (N, n=20) and diabetes group (T1DM, n=40). For T1DM group, streptozotocin was injected into peritoneal cavity of the animals to establish the model of type 1 diabetes. At the 90d after injecting, the expression of HCN2 and HCN4 were detected by immunofluorescent staining, Western-blot and RT-PCR respectively. Results Immuno-fluorescent staining presented the discontinuous punctiform or linear expression of HCN2 in cardiomyocytes membrane, but not for HCN4. However, Both HCN2 and HCN4 were up-regulated at protein(western-blot) and RNA (RT-PCR) levels compared to that of controls. Conclusions The over expression of HCN2 and HCN4 maybe participate in the electrical remodeling in DM rats and the developing of ventricular arrhythmia.
HCN2 / HCN4 / 左心室 / 1型糖尿病 / 大鼠
HCN2 / HCN4 / Left ventricle / T1DM / Rat
[1] Baruscotti M, Bottelli G, Milanesi R, et al. HCN-related channelopathies
[J]. Eur J Physiol, 2010, 460(2): 405-415.
[2] Accili EA, Proenza C, Baruscotti M, et al. From funny current to HCN channels: 20 years of excitation
[J]. News Physiol Sci, 2002, 17:32-37.
[3] Zicha S, Fernández-Velasco M, Lonardo G, et al. Sinus node dysfunction and hyperpolarization-activated (HCN) channel subunit remodeling in a canine heart failure model
[J]. Cardiovasc Res, 2005, 66(3):472-481.
[4] Stillitano F, Lonardo G, Zicha S, et al. Molecular basis of funny current (If) in normal and failing human heart
[J]. J Mol Cell Cardiol, 2008, 45(2):289-299.
[5] 林世荣. 心房颤动患者心房HCN通道及其调节受体基因表达的研究
[D]. 福州: 福建省心血管病研究所, 2005.
[6] Ludwig A, Budde T, Stieber J, et al. Absence epilepsy and sinus dysrhythmia in mice lacking the pacemaker channel HCN2
[J]. EMBO J, 2003, 22(2):216-224.
[7] Stefan H, Juliane S, Georg S,et al. HCN4 provides a ‘depolarization reserve' and is not required for heart rate acceleration in mice
[J]. EMBO J, 2007, 26(21): 4423-4432.
[8] Baruscotti M, Bucchi A, Viscomi C, et al. Deep bradycardia and heart block caused by inducible cardiac-specific knockout of the pacemaker channel gene HCN4
[J]. Proc Natl Acad Sci USA, 2011, 108(4): 1705-1710.
[9] Liu J, Dobrzynski H, Yanni J,et al. Organisation of the mouse sinoatrial node: structure and expression of HCN channels
[J]. Cardiovascular Res, 2007, 73(4): 729-738.
[10]张 玉. 大鼠心肌梗死后梗死周边区HCN2、HCN4、KCNE1及KCNE2表达的动态变化
[D]. 重庆: 重庆医科大学附属第二医院, 2009.
[11]Lin H, Xiao J, Luo X,, et al. Transcriptional control of pacemaker channel genes HCN2 and HCN4 by Sp1 and implications in re-expression of these genes in hypertrophied myocytes
[J]. Cell Physiol Biochem, 2009, 23(4-6):317-326.
[12]刘廷容, 佘强, 吴雪晖. 大鼠心肌梗死后HCN表达的变化及普伐他汀的干预
[J]. 第三军医大学学报, 2008,30(14): 1346-1348.
[13]Muto T, Ueda N, Opthof T, et al. Aldosterone modulates I(f) current through gene expression in cultured neonatal rat ventricular myocytes
[J]. Am J Physiol Heart Circ Physiol, 2007, 293(5): H2710- H2718.
[14]Ye B, Balijepalli RC, Foell JD, et al. Caveolin-3 associates with and affects the function of hyperpolarization-activated cyclic nucleotide-gated channel
[J]. Biochemistry, 2008, 47(47): 12312-12318.
[15] 李 毅, 周华富. HCN4基因在风湿性心脏病二尖瓣狭窄伴心房颤动心房组织中蛋白表达的研究
[J]. 广西医科大学学报, 2010, 27(3): 392-394.
河南省杰出青年科学基金(2005HANCET-15)
/
〈 |
|
〉 |