摘要
目的:研究组蛋白去乙酰化酶8(histone deacetylase 8,HDAC8)在肾性高血压大鼠左心室肥厚中的表达变化及HDAC抑制剂丙戊酸钠(valproic acid sodium,VPA)对心肌肥厚的影响。方法:建立2肾2夹肾性高血压大鼠模型,术后4周开始给药,VPA高剂量(400 mg.kg-1.d-1)组及VPA低剂量(200 mg.kg-1.d-1)组连续腹腔注射VPA给药4周,同时设立假手术组和阳性对照坎地沙坦(10 mg.kg-1.d-1)组,实验结束时测量左心室/体重比值,HE染色检测心肌组织形态学变化,RT-PCR检测心房利钠因子(atrial natriuretic factor,ANF)和HDAC8mRNA表达,Western blotting检测HDAC8的表达情况。结果:HDAC8 mRNA和蛋白表达水平在肾性高血压大鼠心肌组织中明显上调;VPA能够剂量依赖性降低HDAC8的表达,同时VPA治疗组与坎地沙坦组高血压大鼠的左心室肥厚得到明显逆转,表现为心室体重比降低,肥大心肌形态明显改善且ANF的表达下调。结论:HDAC8参与了肾性高血压大鼠心肌肥厚的发病过程,VPA可以下调其表达并部分逆转心肌肥厚。
AIM： To investigate the expression and the role of histone deacetylase 8（HDAC8） in cardiac hypertrophy and the effects of valproic acid sodium（VPA,a histone deacetylase inhibitor） on the expression of HDAC8 and cardiac hypertrophy in two-kidney two-clip（2K2C） renovascular hypertensive rats.METHODS： Male SD rats were randomly divided into sham operation group,2K2C group,high dose VPA（400 mg·kg-1·d-1） treatment group,low dose VPA（200 mg·kg-1·d-1） treatment group and candesartan（10 mg·kg-1·d-1） treatment group.Four weeks after surgery,the rats were intraperitoneally injected with VPA for 4 weeks.Sham operation and 2K2C rats were given vehicle for 4 weeks.All animals were sacrificed 8 weeks after surgery.The ratio of left ventricular weight to body weight（LVW/BW） was calculated and pathological changes of the myocardium were observed with HE staining.The mRNA expression of atrial natriuretic factor（ANF） and HDAC8 was examined by RT-PCR.The protein level of HDAC8 was also measured by Western blotting analysis.RESULTS： Compared with the control rats,the mRNA and protein expression of HDAC8 significantly increased in the myocardium in 2K2C rats while the mRNA and protein expression of HDAC8 was significantly decreased by VPA treatment in 2K2C rats.The mass index（as measured by LVW/BW） and cardiomyocyte cross areas were markedly increased and myocardial fibers were disordered in 2K2C rats,but these parameters were markedly reversed after treated with VPA for 4 weeks,indicating that VPA attenuated cardiac hypertrophy.Moreover,VPA also decreased the mRNA expression of ANF.CONCLUSION： HDAC8 may play an important role in cardiac hypertrophy in 2K2C renovascular hypertensive rats.VPA inhibits the expression of HDAC8 and prevents the development of cardiac hypertrophy.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2012年第2期253-257,共5页
Chinese Journal of Pathophysiology
关键词
组蛋白去乙酰化酶8
高血压
肾性
左心室肥大
丙戊酸钠
大鼠
Histone deacetylase 8
Hypertension
renal
Left ventricular hypertrophy
Valproic acid sodium
Rats
