山茱萸果核醇提物对大鼠肾性高血压及心肌肥厚的影响

Effect of Cornus officinalis Fruit Core Extract on the Cardiac Hypertrophy Induced by Two Kidney Two Clip

目的:观察山茱萸果核甲醇提取物对大鼠肾性高血压及其所致心肌肥厚的作用及机制。方法:建立大鼠肾性高血压(2K2C)模型。将动物分为假手术组、模型组及山茱萸果核醇提物高、低剂量组,每组10只。术后4w进行药物处理,给药4 w后测各组大鼠血压及左室体质量指数(LVM/BM)、心肌形态学变化;Western blot检测心肌组织中NAD(P)H氧化酶亚基P47phox、Nox4的表达情况。结果:模型组大鼠血压及LVM/BM显著高于假手术组,室内压最大上升/下降速率显著下降;给予山茱萸果核醇提物后,各组大鼠血压及LVM/BM显著降低,室内压最大上升/下降速率显著升高,心肌细胞肥大及纤维化程度显著减弱;模型大鼠P47phox、Nox4的蛋白表达较假手术组显著增加,而山茱萸果核组大鼠左心室P47phox、NOX4蛋白表达显著下降,且呈剂量依赖性。结论:山茱萸果核醇提物具有显著降压作用,并能显著抑制肾性高血压大鼠心肌中NAD(P)H氧化酶亚基P47phox和Nox4的表达,这可能是山茱萸果核醇提物改善心脏功能,减缓心肌重构的基础。

Objective：To observe the effect of Cornus officinalis fruit core extract on cardiac hypertrophy induced by two kidney two clip（2K2C） and its mechanism.Methods：Male Sprague-Dawley rats were randomly divided into 4 groups：sham-operated group,model group and treatment groups（300,600 mg/kg）.Rats were intragastric administered medicine for 4 weeks from the fourth week after surgery.Sham-operated and 2K2C rats were given vehicle for 4 weeks.Blood pressure and hemodynamic parameters were measured.Left ventricular weight to body weight（LVM/BM） ratio was calculated.Paraffin-embedded hearts were cut into 5 μm slices,which were stained with hematoxylin-eosin（HE） and Masson for morphological analysis;Western-blot analysis was performed to investigate the effects of Cornus officinalis fruit core extract on the expression of P47phox,Nox4 in myocardium.Results：Compared with sham-operated group,the blood pressure and LVM/BM ratios were markedly elevated in model groups.Meanwhile cardiomyocyte cross sectional areas was markedly increased and myocardial fibers showed disordered arrangement while these parameters were markedly reversed after treatment with Cornus officinalis fruit core extract for 4 weeks.At 8th weeks after operation,model rats developed obvious LV hypertrophy.Cornus officinalis fruit core extract,more significant in high dose,decreased the blood pressure and LVM/BM ratios and reversed the cardiomyocyte hypertrophy and myocardial fibrosis.Moreover,Cornus officinalis fruit core extract decreased the expression of P47phox and Nox4 which elevated in LV in model rats.Conclusion：Cornus officinalis fruit core extract could significantly decrease the blood pressure,reverse cardiac hypertrophy and improve the function of heart which is possibly associated with the down-regulation of P47phox and Nox4.