摘要
目的研究整合素β5和心肌肥大的关系,比较新型血管紧张素Ⅱ-Ⅰ型受体拮抗剂(ARB)奥美沙坦和血管紧张素转换酶抑制剂(ACEI)替莫普利对心肌肥大的作用.方法雄性脑卒中易感型自发性高血压大鼠(SHRSP)33只,5周龄雄性京都种Wistar(WKY)大鼠11只,随机分为SHRSP空白组,SHRSP的奥美沙坦给药组(10 mg·kg-1·d-1),SHRSP的替莫普利给药组(10 mg·kg-1·d-1),WKY作为对照组.给药6周后,取出心脏称重,制作标本进行病理学检查,检测血管紧张素Ⅱ-1型受体(AT1)以及整合素β5的表达量.结果奥美沙坦和替莫普利的使用使SHRSP的收缩压降低,但奥美沙坦比替莫普利的促心肌肥大消退作用更显著.半定量RT-PCR测定表明,SHRSP的AT1和整合素β5的表达量明显高于WKY,奥美沙坦和替莫普利的使用降低了两者的表达量,奥美沙坦的作用更显著.AT1和整合素β5的表达成正相关关系.结论奥美沙坦在抑制心肌细胞肥大和降低AT1、整合素β5的表达量方面比替莫普利有更多获益.整合素β5的表达受抑参与了心肌肥大的消退.整合素β5在心肌细胞的表达可能受到血管紧张素Ⅱ(AngⅡ)通过AT1受体的调节.
Objective To examine the direct relation between integrin 65 and cardiac hypertrophy in vivo, and to compare the effects of a newly developed angiotensin II receptor type 1 （AT1） blocker, olmesartan （ARB） and an angiotensin-converting enzyme inhibitor, temocapril （ACEI） on cardiac hypertrophy in stroke-prone spontaneously hypertensive rats （SHRSP）. Methods Thirty-three SHRSPs and 11 Wistar-Kyoto rats （WKY） were divided randomly into 4 groups： SHRSP-control group, SHRSP- temocapril （10 mg · kg^-1 · d^-1） group, and SHRSP- olmesartan （10 mg · kg^-1 · d^-1） group. WKY-control group. Six weeks after intervention, the hearts were taken out for the weight measurement, pathological examination and the mRNA expression of AT1 receptor and integrin β5 were detected. Results Olmesartan or temocapril significantly reduced systolic blood pressure. However, the reduction in cardiac hypertrophy was greater in SHRSP olmesartan control group than that in temocapril group. Multiplex reverse transcription-polymerase chain reaction revealed significantly higher mRNA expression of AT1 receptor, and integrin 65 in SHRSP control group than that in WKY group. The correlation between the expression of integrin 65 and AT1 receptor was positively related. Conclusions These observations suggest that compared with temocapril, olmesartan has a greater beneficial effect on myocyte hypertrophy and that down-regulation of AT1 receptor and suppression of integrin 65 participate in the regression of pressure-induced cardiac hypertrophy in vivo. Our results also suggest that integrin expression by myocytes might be modulated by angiotensin II via AT1 receptor.
出处
《中国心血管杂志》
2007年第2期90-92,95,共4页
Chinese Journal of Cardiovascular Medicine
