丙戊酸钠对肾性高血压大鼠肾脏纤维化的作用及对组蛋白去乙酰化酶表达的影响

Effects of sodium valproate on renal fibrosis and histone deacetylase expression in renal hypertensive rats

目的研究丙戊酸钠(VPA)对肾性高血压大鼠肾脏纤维化和组蛋白去乙酰化酶(HDACs)表达的影响。方法 SD大鼠分为假手术组、模型组、高、低剂量VPA组和阳性对照组,连续给药4周,检测大鼠血压、肾功能、肾脏纤维化及肾脏HDAC2和HDAC8的表达变化。结果模型组大鼠的主动脉收缩压和舒张压(ASBP,ADBP)、左室收缩末压和左室舒张末压(LVESP,LVEDP)、Scr、BUN及肾脏HDAC2和HDAC8表达均明显升高,出现了明显的肾脏纤维化。经VPA与氨氯地平治疗后,上述各项指标显著降低,血流动力学紊乱、肾功能及肾脏纤维化程度明显改善。结论 VPA对肾性高血压大鼠肾脏纤维化有明显改善作用,其机制可能与下调HDAC2及HDAC8的表达有关。

Objective To investigate the effects of valproic acid sodium （VPA） on renal fibrosis and the expression of histone deacetylase 2 （HDAC2） and HDAC8 in renovascular hypertensive rats. Methods Male SD rats were randomly divided into sham operation group, model group, high and low doses VPA （400, 200 mg · kg^-1 · d^-1 ） groups, and amlodipine （ 10 mg · kg^-1 · d^-1） group. At the time of 4 weeks after surgery, VPA was given by intraperitoneal injection and amlodipine was given by gastric gavage for 4 weeks. Sham - operated rats were given sodium chloride. Hemodynamic parameters and renal function was detected. The interstitial collagen contents of the kidney tissue were observed with Masson staining. The protein levels of HDAC2 and HDAC8 were also measured by western blotting analysis. Results Aortic systolic blood pressure （ASBP） , aortic diastolic blood pressure （ADBP）, the left ventricle end - systolic pressure （ LVESP ） , left ventricle end - diastolic pressure （LVEDP）, serum creatinine （Scr） and blood urea nitrogen （BUN） increased in model rats. Treatment with VPA and amlodipine for 4 weeks markedly decreased these parameters of model rats, blood pressure, renal function and diffuse interstitial fibrosis exhibited significant improvement. The expression of HDAC2 and HDAC8 also increased in kidneys of model hypertensive rats, however, their expression levels were decreased significantly by VPA or amlodipine. Conclusion VPA had significant improvement effects in renal function and renal fibrosis in renovascular hypertensive rats partially by inhibition of HDAC2 and HDAC8 expression in kidneys.