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目的观察Candesartan早期治疗对SHR大鼠心肌纤维化及心肌AT1、AT2表达的影响,探讨其抗心肌纤维化的机制。方法选取4周龄的雄性自发性高血压大鼠SHR(Spontanous Hypertensive Rat,SHR)及与之年龄性别相配的正常大鼠WKY;动物分组:WKY组、SHR组、Candesartan治疗组(SHR-Can组,给药4周后停药,继续喂养至24周);尾袖法测定大鼠血压,断头取血,称量全心与左心质量,计算心体比与左室质量指数;放免法测定血浆及心肌AII水平;免疫组化法检测心肌组织中AT1、AT2的表达;Western blotting法测定心肌AT1、AT2的表达水平;天狼星红染色测定心肌胶原指数。结果 8周龄后,与SHR组相比,SHR-Can组血压明显下降并持续24周(P<0.05);SHR-Can组心体比及左室质量指数明显低于SHR组(P<0.05);SHR组血浆中AII水平与WKY组相比明显增高(P<0.01),SHR-Can组与SHR组相比降低(P<0.05);心肌组织AII含量SHR-Can组明显低于SHR组(P<0.05)。心肌免疫组化染色示:与WKY相比,SHR大鼠AT1、AT2明显增高(P<0.05);与SHR相比,SHR-Can组心肌中AT1、AT2明显减少(P<0.05)。Western blotting结果示:SHR组AT1、AT2表达水平明显高于WKY组(P<0.05);SHR-Can组AT1、AT2表达水平明显降低(P<0.05)。天狼星红染色心肌胶原含量SHR-Can组明显低于SHR组(P<0.05)。结论 Candesartan早期治疗可抑制SHR大鼠高血压的形成与发展,也可抑制SHR心肌纤维化并降低心脏指数,还能降低SHR心肌AT1、AT2的表达,Candesartan抑制心肌纤维化可能与心肌局部AT1、AT2表达水平有关。
Objective To observe the effects of early Candesartan treatment on myocardial fibrosis and the expression of AT1 and AT2 in SHR rats and the mechanism of anti-myocardial fibrosis. Methods SHR (Spontaneous Hypertensive Rat, SHR) and WKY (normal male WKY) rats of 4-week-old male spontaneously hypertensive rats were divided into three groups: WKY group, SHR group, Candesartan treatment group , Discontinued after 4 weeks of administration, and continued to be fed until 24 weeks); blood pressure was measured by caudal sleeves and blood was decapitated, the whole heart and left ventricle were weighed, and the ratio of cardiocervical and left ventricular mass was calculated; The levels of plasma and myocardial AII were measured. The expression of AT1 and AT2 in myocardium was detected by immunohistochemistry. The expressions of AT1 and AT2 in myocardium were detected by Western blotting. The collagen index was measured by Sirius red staining. Results After 8 weeks of age, the blood pressure of SHR-Can group decreased significantly for 24 weeks (P <0.05) compared with that of SHR-Can group. The SHR-Can group was significantly lower than SHR group ). The level of AII in SHR group was significantly higher than that in WKY group (P <0.01), SHR-Can group was lower than SHR group (P <0.05) (P <0.05). Myocardial immunohistochemical staining showed that compared with WKY, the levels of AT1 and AT2 in SHR-Can group were significantly increased (P <0.05) compared with those in SHR-Can group. The results of Western blotting showed that the expression of AT1 and AT2 in SHR group was significantly higher than that in WKY group (P <0.05). The expression of AT1 and AT2 in SHR-Can group was significantly decreased (P <0.05). Sirius red staining of myocardial collagen content SHR-Can group was significantly lower than SHR group (P <0.05). Conclusion Early Candesartan treatment can inhibit the formation and development of hypertension in SHR rats. It can also inhibit cardiac fibrosis and reduce cardiac index in SHR rats. It can also reduce the expression of AT1 and AT2 in SHR myocardium. Candesartan inhibits myocardial fibrosis possibly related to myocardial AT1, AT2 expression level.