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目的:观察AngⅡ1型受体(ATl)拮抗剂氯沙坦(Losartan)的逆转急性容量和压力超负荷心肌肥大(MH)作用。方法:选择60只雄性SD大鼠,每组12只,随机分为5组:腹腔动静脉造瘘容量超负荷组(VO组);容量超负荷+治疗组(LOSV组):腹主动脉部分结扎压力超负荷组(PO组);压力超负荷+治疗组(LOSP组)及对照组(CON组)。对比检测术后第10天和第20天的收缩压(SBP)、左室重量指数(LVMI)、心肌及血浆AngⅡ含量。电镜观察第20天心肌超微结构变化。结果:①两模型组LVMI、SBP及心肌AngⅡ第10天和第20天均显著升高(P<0.05,与CON组比),而血浆AngⅡ均仅于第20天才较对照组明显升高(P<0.05);②AT1受体被阻断后第10天,两治疗组LVMI及SBP较各自未治疗组均明显下降(P<0.05)(LOSP组LVMI下降幅度无统计学意义),但仍高于CON组(P<0.05)。LOSV组和LOSP组心肌AngⅡ较各自未治疗组均有升高,前者有统计学差异(P<0.05,与VO组比较)。两治疗组血浆AngⅡ较未治疗组均明显升高(P<0.05);③ATl受体被阻断后第20天,两治疗组LVMI、SBP和LOSP组心肌AngⅡ较各自未治疗组均明显降低(P<0.05),LOSV组心肌AngⅡ下降不明显(P>0.05),上述指标均高于CON组(P<0.05)。两治疗组血浆AngⅡ较各自未治疗组明显升高(P<0.05)。电镜示两治疗组心肌线粒体空泡样化较各自未治疗组均明显好转;④两模型组LVMI与心肌AngⅡ及血浆AngⅡ均呈显著正相关(P<0.01),前者相关强度高于后者。结论:AT1受体拮抗剂Losartan早期具显著逆转MH作用。
OBJECTIVE: To observe the effects of Losartan, an angiotensin II type 1 receptor (AT1) antagonist, on the reversal of acute capacity and pressure overload in myocardial hypertrophy (MH). Methods: Sixty male Sprague-Dawley rats were randomly divided into 5 groups: OVX volume overload group (VO group); volume overload + LOSV group Ligation stress overload group (PO group); pressure overload + treatment group (LOSP group) and control group (CON group). The systolic blood pressure (SBP), left ventricular mass index (LVMI), myocardial and plasma AngⅡcontent were detected on the 10th and 20th postoperative day. Electron microscopy on the 20th day myocardial ultrastructure changes. Results: ①The levels of LVMI, SBP and myocardial Ang Ⅱ in both groups were significantly increased on the 10th and 20th days (P <0.05, compared with the CON group), while the levels of plasma AngⅡ were significantly increased only on the 20th day P <0.05). ② On the 10th day after the blockade of AT1 receptor, the LVMI and SBP in the two treatment groups were significantly lower than those in the untreated group (P <0.05) (LVMI decline was not significant in the LOSP group) In CON group (P <0.05). The levels of Ang Ⅱ in LOSV group and LOSP group were significantly higher than those in untreated group (P <0.05, vs VO group). Compared with the untreated group, the Angiotensin Ⅱ in the two treatment groups were significantly increased (P <0.05); ③Twenty days after the AT1 receptor was blocked, the myocardial AngⅡ levels in LVMI, SBP and LOSP groups were significantly lower than those in the untreated group P <0.05). The decrease of Ang Ⅱ in LOSV group was not significant (P> 0.05). The above indexes were all higher than those in CON group (P <0.05). Angiotensin Ⅱ in the two treatment groups was significantly higher than that of the untreated group (P <0.05). Electron microscopy showed that myocardial mitochondrial vacuolization was significantly improved in both treatment groups compared with those in untreated group. (4) There was a significant positive correlation between LVMI and myocardial AngⅡ and plasma AngⅡ (P <0.01). Conclusion: Losartan, an AT1 receptor antagonist, had a marked reversible effect on MH.