减阻剂改善自发性高血压大鼠主动脉重塑

发布时间：2018-10-09 19:53

【摘要】：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(P0.05),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(P0.05);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(P0.05);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。
[Abstract]:Objective (DRP) is a kind of linear polymer compound which can reduce fluid resistance and increase shear stress of fluid. The effect of intravenous DRP on aortic remodeling of (SHR) in spontaneously hypertensive rats was observed. Methods Twenty-four 8-week-old male SHR patients were randomly divided into 3 groups: (SHR NS group (n = 10), (SHR NS group (n = 10) and SHR20 mg/L DRP group (n = 10). Every other day, NS or different doses of DRP;8 were given to (WR) of age-matched male Wistar rats as control group (WR NS group), and NS. was given intravenously. Body weight, systolic blood pressure of caudal artery, heart rate. 60 days after anesthesia were recorded before and every 20 days. The level of endothelin (ET) in serum of rats was detected by enzyme-linked immunosorbent assay (Elisa). The ascending aorta of rats was isolated and the morphology of aorta was observed by paraffin embedded HE staining. The expression of endothelin 1 (ET-1) in aorta was detected by immunohistochemistry. Results there was no significant difference in body weight and heart rate among SHR groups. Blood pressure in SHR20 mg/L DRP group was significantly lower than that in SHR NS group (P0.05), but there was no significant difference in blood pressure between SHR 10 mg/L DRP group and SHR NS group. Compared with SHR NS group, the serum ET level in 10mg/L DRP group and SHR 20 mg/L DRP group was significantly lower than that in SHR 20 mg/L DRP group. Aortic HE staining showed that the thickness of aortic media was significantly thicker in NS group than that in WR NS group (P0.05). Compared with the SHR NS group, the aortic medial thickness in the SHR 10mg/L DRP group was significantly lower than that in the SHR20 mg/L DRP group (P0.05). There was no significant difference between the SHR 10 mg/L DRP group and the WR NS group in the aortic media thickness between the SHR 20mg/L DRP group and the WR NS group. Immunohistochemical staining of aorta showed that the expression of Tet 1 in vascular endothelium and medial smooth muscle was significantly higher in SHR rats than in WR rats. There was no significant difference in aortic ET-1 between SHR10 mg/L DRP group and SHR 20 mg/L DRP group after intravenous administration of DRP. The aortic ET-1 in SHR20 mg/L DRP group was significantly lower than that in SHR10 mg/L DRP group and SHR 20 mg/L DRP group. Conclusion intravenous application of DRP can improve aortic remodeling of SHR, and its mechanism may be related to the inhibition of ET-1 expression by DRP by increasing blood shear stress in aorta. Drag reducers may provide a new idea for the treatment of aortic remodeling induced by hypertension.
【作者单位】：南方医科大学南方医院心内科;
【基金】：广东省自然科学基金(S2012010009024)
【分类号】：R544.1

【参考文献】