非选择性内皮素受体拮抗剂对肥厚心肌局部血管紧张素系统的影响

Effect of nonselective endothelin receptor antagonist on local angiotensin system of myocardial hypertrophy

目的:探讨内皮素受体拮抗剂对肥厚心肌局部血管紧张素系统的影响及可能作用机制。方法:24只大鼠随机分为对照组、心肌肥厚组和内皮素受体拮抗剂组。测定左室指数,采用免疫组化法测定心肌组织中血管紧张素受体-1(AT1R),放射免疫法测定心肌组织血管紧张素Ⅱ(AngⅡ)含量,分光光度法测心肌组织血管紧张素转化酶(ACE)活性,部分心肌组织进行HE、VG染色。结果:与对照组相比,心肌肥厚组左室指数、左室全心比、ACE活性、AngⅡ浓度及AT1R阳性表达率增加均有统计学意义(P<0.05)。与心肌肥厚组相比,内皮素受体拮抗剂组左室指数、左室全心比、ACE活性、AngⅡ浓度及AT1R阳性表达灰度值降低均有统计学意义(P<0.05),但ACE活性、AT1R阳性表达灰度值仍高于对照组(P<0.05),而其他指标差异无统计学意义。结论:去甲肾上腺素诱导的心肌肥厚大鼠心肌组织局部血管紧张素系统活化,导致心肌细胞肥大,胶原增生。PD142893可以部分抑制这一作用,内皮素可能参与了血管紧张素系统活化过程。

To explore the effect and mechanism of endothelin receptor antagonist on local angiotensin system of hypertrophic myocardial tissue. METHODS： Twenty four rats were randomly divided into 3 groups, control group （CG）, hypertrophy group （HG） and endothelin receptor antagonist group （EG）. The ratios of left ventricle weight to body weight （LVW/BW） and left ventricle weight to heart weight （LVW/HW） were measured to reflect myocardial hypertrophy. Protein expression of ATIR was detected by immunohistochemistly. The concentration of Ang Ⅱ was determined by fla. Activity of ACE was examined by spectmphotometly. A piece of myocardial tissue was observed in light microscope after HE or VG dyeing. TESULTS： （ 1 ） In comparison to CG, LVW/BW, LVW/HW, ACE activity, the concentration ofAng Ⅱ and the expression of AT1R of HG were increased significantly （P 〈0.05）. （2） In EG, ACE activity, the concentration of Ang Ⅱ and the expression of AT1R were reduced markedly compared with HG （ P 〈 0,05 ）, but ACE activity and the expression of AT1R were still higher than those in CG （ P 〈 0.05）. CONCLUSION： Local angiotensin system is activated in myocardial hypertrophic tissue induced by ne, which leads to hypertrophy of myocardial cell and hyperplasy of collagen. Endothelin-1 probably participates in the activation, which could be inhibited partially by endothelin receptor antagonist, pd142893.