减阻剂改善自发性高血压大鼠主动脉重塑

Drag-reducing Polymer Improve Aortic Remodeling in Spontaneous Hypertensive Rat

目的减阻剂(DRP)是一种可以减少流体阻力、增加流体剪切应力的线性高分子化合物,本实验观察静脉应用DRP对自发性高血压大鼠(SHR)主动脉重塑的影响。方法 24只8周龄雄性SHR随机分为3组:SHR+生理盐水组(SHR+NS组)、SHR+10 mg/L DRP组、SHR+20 mg/L DRP组,隔日给予静脉注射NS或不同剂量的DRP;8只年龄匹配的雄性Wistar大鼠(WR)作为对照组(WR+NS组),给予静脉注射NS。实验开始前及每20天记录大鼠体重、尾动脉收缩压、心率。60天后大鼠麻醉后心脏取血,酶联免疫吸附测定法检测大鼠血清内皮素(ET)水平。处死大鼠,分离大鼠升主动脉,石蜡包埋,HE染色观察主动脉形态结构,免疫组织化学法检测主动脉内皮素1(ET-1)表达。结果 SHR各组间体重、心率无显著差异。SHR+20 mg/L DRP组血压较SHR+NS组明显降低(P<0.05),而SHR+10 mg/L DRP组与SHR+NS组血压无统计学差异。与SHR+NS组相比,SHR+10mg/L DRP组及SHR+20 mg/L DRP组血清ET水平显著降低,差异具有统计学意义。主动脉HE染色显示,与WR+NS组相比,SHR+NS组主动脉中膜厚度明显增厚(P<0.05);静脉应用DRP后,与SHR+NS组相比,SHR+10mg/L DRP组、SHR+20 mg/L DRP组主动脉中膜厚度均显著降低(P<0.05);SHR+10 mg/L DRP组、SHR+20mg/L DRP组与WR+NS组之间主动脉中膜厚度无统计学差异。主动脉免疫组织化学染色显示,ET-1在血管内皮及中层平滑肌均有表达,SHR大鼠主动脉表达明显高于WR大鼠;经静脉应用DRP后,SHR+10 mg/L DRP组、SHR+20 mg/L DRP组主动脉ET-1较SHR+NS组显著降低,SHR+10 mg/L DRP组与SHR+20 mg/L DRP组之间主动脉ET-1无显著差异。结论静脉应用DRP可改善SHR主动脉重塑,其机制可能与DRP通过增加主动脉内血液剪切应力抑制了ET-1表达有关,减阻剂可能为治疗高血压引起的主动脉重塑提供新的思路。

Aim Certain long-chain water-soluble polymer,known as drag reducing polymer( DRP),when added in minute concentrations,have been shown to decrease peripheral vascular resistance. In this study,the effect of DRP on the hypertension-induced aortic remodeling was evaluated in spontaneous hypertensive rat( SHR). Methods 24 male SHR were divided into three groups; 8 male,age matched Wistar rats( WR) as control. The experimental groups of SHR received an intravenous injection of normal saline( SHR + NS group),10 mg / L DRP( SHR + 10 mg / L DRP group),20 mg / L DRP( SHR + 20 mg / L DRP group),respectively. The control group only received equal-volume of normal saline( WR + NS group). The whole study spanned 2 months,and body weight,heart rate,systolic blood pressure were measured at the beginning and every 20 days. Then blood sample and aorta were collected. Serum endothelin( ET) was measured by enzyme-linked immunosorbent assay( ELISA). The aorta was stained by hematoxylin-eosin( HE),andaortic medial thickness was evaluated for each section. The expression of endothelin-1( ET-1) of aorta was examined by immunohistochemistry. Results There was no significant difference between the SHR groups in body weight and heart rate during the treatment period. Systolic blood pressure was significantly reduced in SHR + 20 mg / L DRP group than in SHR + NS group( P < 0. 05),while there was no significant difference between SHR + 10 mg / L DRP group and SHR + NS group. Compared with the SHR + NS group,the levels of serum ET decreased in SHR + 10 mg / L DRP group and SHR +20 mg / L DRP group( P < 0. 05). The medial thickness of the aorta was reduced in SHR + 10 mg / L DRP group and SHR+ 20 mg / L DRP group compared with SHR + NS group. The expression of ET-1 of the aorta was significantly attenuated in SHR + 10 mg / L DRP group and SHR + 20 mg / L DRP group. Conclusions These results suggest that chronic treatment with DRP can protect against aortic remodeling in spontaneous hypertensive rats,possibly by improving blood shear stress in aorta. DRP may offer a new approach to the treatment of aortic remodeling caused by hypertension.