Candesartan早期治疗对SHR大鼠心肌心肌纤维化及AT1，AT2表达的影响

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（SpontanousHypertensiveRat，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，称量全心与左心重量，计算心体比与左室重指数；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；Westernblotting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（1）4周龄SHR组，SHR—Can组与WKY三者血压无明显差异（P〉0．05）；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组心体比及左室指数明显低于SHR组（4．43±0．39VS3．45±0．17，P〈0．05；3．75s0．29VS2．824-0．22，P〈0．05）；与WKY组相比，SHR组血浆中AII水平明显增高（1609．63±254．73VS651．77±213．86，P〈0．01）；与SHR组相比，SHR—Can组显著降低（1201±297．04VS1609．63±254．73，P〈0．05）；心肌组织AII含量SHR—Can组明显低于SHR组（287．25±38．13VS465．21±52．15，P〈0．05）。（2）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ATl、AT2明显减少（P〈0．05）；Westernblotting结果示：SHR组AT1、AT2表达水平明显高于WKY组（P〈O．05）；SHR—Can组AT1、AT2表达水平显著明显降低（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（1）Candesaxtan早期治疗可抑制SHR大鼠高血压的形成与发展（2）Candesartan早期治疗抑制SHR心肌纤维化并降低心脏指数；（3）Candesartan早期治疗降低SHR心肌心肌AT1、AT2的表达，（4）Candesartan抑制?

The effect of Expression of AT1, AT2 and fibrosis in Heart of SHR with Candesartan transiently prehypertension treatment

Objective To investigate the effect of Expression of AT1, AT2 and fibrosis in Heart of Spontanous Hypertensive Bat （SHR） transiently prehypertension treated with Candesartan, and explore the machanisis of the myacardium fibrosis in SHR Methods Four - week - old male SHR and age - matched normotensive Wistar - Kyoto （WKY） rats were selected. WKY rats, SHR and transiently （ between 4 - 8 weeks of age） treated SHR with Candesartan （ SHR - Can：20mg/kg. day）, Rats were followed up until week 24 of age. The blood pressure（BP） was determined by tail - cuff. Heart weight and left ventricular weight（LVW） were used to calculate heart mass/body mass ratio（HBR） and left ventricular mass index（LVMI）. Radioimmunoassay was used to determine level of plasma or load heart All. Immunohistochemistry was performed to detect the expression of AT1 and AT2 in myocardium. Expression of AT1 and AT2 in heart was detected by Western blotting. Results Blood pressure in four - week - old SHR was no significantly differently with that in WKY（ P 〉 0.05 ） ; After 8 weeks Compared with SHR, Blood pressure in SHR - Can group was highly decreased （ P 〈 O. 05 ）, HBR and LVMI was remarkably lower （P 〈 0.05）, plasma All in SHR was highly increased compared with WKY（P 〈 0.01 ）. Compared with $HR, plasma AII and loading heart in SHR - Can greup was remarkably decreased. （2） Compared with WKY, AT1 in heart of SHR was significantly higher（ P 〈 0.05 ） and that was remarkable lower in SHR - Can group. Expression of AT,AT2 in SHR heart was greatly increased and that in SHR - Can was remarkly reduced, compared with $HR, capacity of collagen in SHR - Can group was greatly reduced（P 〈 0.05 ） Conclusion （1） Candesartan transient prehypertensivetreetment could inhibit progression of blood presure （2）Candesartan treated transient prehypertensive SHR could inhibit expression of AT1 and AT2 , fibresis in heart and reduce LVMI. （ 3 ） Discrepancy of expression of between AT1 and AT2