摘要
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 investigate the effect of candesartan on the expressions of AT1 and AT2, and fibrosis in the heart of spontaneous hypertensive rats （SHR） and explore the mechanisms. Methods Four-week-old male SHR and agematched normotensive Wistar-Kyoto （WKY） rats were selected and divided into a WKY group, SHR group and SHR-ean group （transiently treated with candesartan 20 mg/kg？ day between 4-8 weeks of age）. The rats were followed up until 24 weeks of age. The blood pressure （BP） was determined by tail-cuff. Heart weight and left ventricular weight （LVW） were used to calculate the heart mass/body mass ratio （HBR） and left ventricular mass index （LVMI）. Radioimmunoassay was used to determine the AⅡ levels of plasma and myocardium, lmmunohistochemistry was performed to detect the expressions of AT1 and AT2 in myocardium. The expressions of AT 1 and AT2 in myocardium were detected by Western blotting. Results The blcod pressure in four-week-old SHR was no significantly different from that in WKY （P 〉0.05）. After 8 weeks, compared with SHR, the blood pressure in the SHR-ean group significantly decreased （P〈0.05）, HBR and LVMI were remarkably lower （P〈0.05）, plasma All in SHR significantly increased compared with WKY （P 〈 0.01）. Campared with SHR, plasma All and loading heart in the SHR-can group significantly decreased. Compared with WKY, AT 1 in myoeardium of SHR was significantly higher （P 〈 0.05） and that was significantly lower in the SHR-can group. The expressions of AT and AT2 in SHR myocardium significantly increased and that in SHR-can remarkably reduced. Compared with SHR, the capacity of oollagen in the SHR-can group significantly reduced （P 〈 0.05）. Conclusions Candesartan transiently prehypertensive treatment could inhibit the progression of blood pressure, the expressions of AT1 and AT2, and fibrosis in heart, and reduce LVMI. The discrepancy of expressions of AT1 and AT2 may be related to myocardium fibrosis of SHR.
出处
《中国校医》
2010年第11期827-830,共4页
Chinese Journal of School Doctor
