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目的氯沙坦早期短暂治疗对自发性高血压大鼠(SHR)血压及心肌纤维化的影响。方法选取4周龄雄性SHR随机分为氯沙坦早期给药组(SHR-Los4组,20mg/(kg.d),4周龄接受氯沙坦治疗4周后停药)、氯沙坦成年后给药组(SHR-Los12组,20mg/(kg.d),大鼠养至12周龄接受氯沙坦治疗4周后停药)或蒸馏水(SHR组),周龄性别匹配WKY大鼠作为正常对照,每组8只。停药后采用尾袖法测定大鼠血压,随访至24周;然后断头取血,称量全心与左心质量,计算心体比(心脏质量/体质量)与左心室质量指数(LVMI,左心室质量/体质量);天狼星红染色测定心肌胶原容积分数,放免法测定血浆及心肌血管紧张素Ⅱ(AngⅡ)水平。结果与SHR组比较,SHR-Los4组8周时血压明显降低(P<0.05),于12至20周血压维持于较低水平;24周龄时,血压仍明显低于SHR组(P<0.05);SHR-Los12组16周时血压明显降低,20周血压上升,于24周时与SHR组比较,两者血压差异无统计学意义(P>0.05)。SHR-Los4组心体比、LVMI、心肌胶原容积分数明显低于SHR组(P<0.05),但与SHR-Los12组比较,两组差异无统计学意义(P>0.05)。SHR-Los4组血浆及心肌组织AngⅡ水平明显低于SHR组(P<0.01);而SHR-Los12组血浆及心肌组织AngⅡ含量高于SHR组,但差异无统计学意义(P>0.05)。结论氯沙坦早期短暂治疗可延缓SHR高血压的进展,抑制心肌纤维化,其机制可能与抑制肾素血管紧张素系统活性有关。
Objective To investigate the effects of early losartan short-term treatment on blood pressure and myocardial fibrosis in spontaneously hypertensive rats (SHR). Methods Four-week-old SHRs were randomly divided into three groups: losartan group (SHR-Los4 group, 20mg / (kg · d)), losartan group (SHR-Los12 group, 20mg / (kg · d)), rats were given up to 12 weeks of treatment losartan treatment for 4 weeks after discontinuation) or distilled water (SHR group), week age sex matched WKY rats As a normal control, each group of 8. After discontinuation, the blood pressure was measured by the tail cuff method and followed up for 24 weeks. The blood samples were collected for decapitation and the whole heart and left ventricle were weighed to calculate the ratio of cardiac mass to body mass and left ventricular mass index , Left ventricular mass / body weight); myocardial collagen volume fraction was determined by Sirius red staining, and plasma and myocardial angiotensin Ⅱ (AngⅡ) levels were determined by radioimmunoassay. Results Compared with SHR group, blood pressure decreased significantly at 8 weeks in SHR-Los4 group (P <0.05), and remained lower at 12 to 20 weeks; blood pressure was still lower at SHR than that in SHR group at 24 weeks (P <0.05) The blood pressure decreased significantly at 16 weeks in SHR-Los12 group and increased at 20 weeks. There was no significant difference in blood pressure between SHR-Los12 group and SHR group at 24 weeks (P> 0.05). Compared with SHR group, SHR-Los4 group had lower cardiac volume ratio, LVMI, and myocardial collagen volume fraction than SHR group (P <0.05), but there was no significant difference between two groups (P> 0.05). The levels of AngⅡ in plasma and myocardium in SHR-Los4 group were significantly lower than those in SHR group (P <0.01), while those in SHR-Los12 group were higher than those in SHR group (P> 0.05). Conclusion Early treatment with Losartan can delay the progression of hypertension in SHR and inhibit myocardial fibrosis. The mechanism may be related to the inhibition of renin angiotensin system activity.