高血压大鼠血管外周脂肪组织对血管调节功能的改变及他汀类药物治疗的影响

Functional changes of perivascular adipose tissue in hypertensive rats and the effects of statins therapy

目的:观察自发性高血压大鼠(SHR)血管外周脂肪组织释放血管舒张因子功能的改变及他汀类药物干预的影响。方法:SHR10周龄后,分别给予阿托伐他汀钙50mg/kg.d,血脂康2400mg/kg.d干预16周。观察阿托伐他汀钙干预组(SHR-A)、血脂康干预组(SHR-X)、对照SHR组和WKY组的血压(SBP)变化;于26周龄,把各组大鼠的相邻的两段胸主动脉环分为血管外周脂肪亚组和裸血管亚组,予10-6mmol/L苯肾上腺素(PHE)刺激,比较两亚组血管收缩力的差异;用液体转移的方法,观察孵育血管外周脂肪组织的培养液对裸血管张力的影响。结果:①WKY组、SHR-A组、SHR-X组SBP实验前后无显著变化,SHR组的SBP实验结束时显著高于实验开始时;②WKY组、SHR-A组、SHR-X组血管外脂肪亚组的收缩力低于裸血管亚组的收缩力,而SHR两血管亚组的收缩力无差别;③把WKY组,SHR-A组,SHR-X组孵育的血管外脂肪的培养液转移到裸血管均诱发其快速舒张,而SHR组则无显著血管舒张反应。结论:WKY的血管外周脂肪组织释放一种可转移性血管舒张因子,降低血管对苯肾上腺素的反应性,调节血管功能。而SHR的血管外周脂肪组织这种血管调节作用减弱;血管外周脂肪组织这种功能异常可能是高血压血管功能异常的病理基础之一。他汀类药物治疗在修复SHR血管外周脂肪组织这种功能异常的同时,还能减缓SHR血压上升。

AIM ： To study the functional changes of perivascular adipose tissue （PVAT） in SHR and the effects of statins therapy. METHODS： Adult SHR at 10 weeks of age were treated with atorvastatin （50 mg · kg^-1 · d^-1 ） or Xuezhikang （2 400 mg^-1·kg^-1· d^-1 ） for 16 weeks. Age - matched untreated SHR and WKY were used as controls. Tail - cuff systolic blood pressure （SBP） was measured at the beginning and the end of experiment. Thoracic aorta was divided into two segments ： vessel without PVAT [ Fat （ - ） ] and vessel with PYAT [ Fat （ ＋ ） ]. The differences in contractile force induced by phenylephrine in these vessels from the four groups of rats were compared. RESULTS： SBP in SHR was significantly higher than that in WKY at the beginning of the experiment. SBP of SHR treated with statins and WKY control did not show statistical difference during the treatment period. Contractile force of Fat（ ＋ ） vessels in WKY and SHR groups treated with statins was lower than that in Fat （ - ） vessels. There was no difference in the contractile force between Fat （ ＋ ） and Fat （ - ） vessels in SHR control. Bathing solution transferred from Fat（ ＋ ） vessels in WKY, SHR - A, and SHR - X caused a relaxation response in Fat （ - ） vessels, but not in control SHR. CONCLUSIONS： PVAT in WKY released a transferable relaxation factor which attenuated the responsiveness of the vessels to phenylephrine. The release or the action of this relaxation factor was reduced in the SHR. Treatment with statins restored the release or the action of this relaxation factor in the SHR.