三种降压药对自发性高血压大鼠肠系膜动脉细胞凋亡的影响

目的：比较血管紧张素Ⅱ受体拮抗剂——氯沙坦（科素亚）、二氢吡啶类钙拮抗剂——苯磺酸氨氯地平（络活喜）、血管紧张素转换酶抑制剂——培哚普利（雅施达）三种不同作用机制的降压药对自发性高血压大鼠肠系膜动脉细胞凋亡的影响。方法：将11周龄雄性自发性高血压大鼠（spontaneously hy-pertensive rat,SHR）随机分成氯沙坦组（SHR-los组）、苯磺酸氨氯地平给药组（SHR-nor组）、培哚普利给药组（SHR-per组）与空白对照组（SHR对照组）,各10只,另设11周龄雄性正常血压大鼠（Wistar-Kyoto rat,WKY）作正常对照组（WKY组）。实验前及实验开始后每4周测一次大鼠尾动脉收缩压。饲养8周后,检测bax、bcl-2和P53基因表达及caspase-3酶活性以了解肠系膜二、三级动脉细胞凋亡情况。结果：氯沙坦、苯磺酸氨氯地平、培哚普利能显著降低SHR动脉收缩压,三组间降压效果差异无统计学意义（P〉0.05）。bax、bcl-2和P53基因在各组肠系膜动脉中均有表达,各给药组较SHR对照组在基因表达上显示出抑制细胞凋亡作用,尤以苯磺酸氨氯地平最明显（P〈0.05）。caspase-3活性SHR对照组最高,WKY组最低（P〈0.01）,三个给药组介于两者之间（P〈0.01）,其中氯沙坦组和培哚普利组差异无统计学意义,苯磺酸氨氯地平组caspase-3活性较前两组低（P〈0.01）。结论：氯沙坦、苯磺酸氨氯地平和培哚普利除了有降压作用外,还有抑制阻力血管细胞凋亡的作用,在抑制大鼠肠系膜动脉细胞凋亡方面苯磺酸氨氯地平更优。

Study of the protective effect of three kinds of antihypertensive drugs in the apoptosis of mesenteric artery in SHR

Objective: To compare the effects of three different antihypertensive drugs consisting of angiotensinⅡreceptor antagonist losartan,dihydropyridine calcium antagonist amlodipine besylate and angiotensin converting enzyme inhibitors perindopril on cell apoptosis in mesenteric artery of spontaneously hypertensive rat.Methods: The 11-week old male SHR were randomly divided into losartan intervention group(SHR-los),amlodipine besylate intervention group(SHR-nor),perindopril intervention group(SHR-per)and the blank control group(SHR).The sex and age matched WKY were used as normal control group.Systolic blood pressure was measured by a tail-cuff method before and every four weeks after experiment.8 weeks later,the level of Bax,bcl-2 and P53 expression and caspase-3 activity were measured.The mesenteric artery cell apoptosis was observed.Results: Losartan,amlodipine besylate and perinopril lowered systolic blood pressure of SHR significantly(P <0.01)and no significant difference was found among the three drug-treated groups(P >0.05).Bax,bcl-2 and P53 genes expressed in each group of mesenteric artery,drug-treated groups displayed that they could inhibit cell apoptosis by expression of some related genes such as Bax,bcl-2 and P53 genes,especially in SHR-nor group(P <0.05).Caspase-3 activity of SHR group was the highest and that of WKY group was the lowest.Caspase-3 activity was lower in the three drug-treated groups than that in the SHR group and higher than that in the WKY group(P <0.01).No significant difference was found between SHR-los and SHR-per group.Caspase-3 activity in SHR-nor group was lower than that of the other two drug-treated groups(P <0.01).Conclusion: Besides lowering blood pressure,Losartan,amlodipine besylate.and perindopril may have cardiovascular protective effect by preventing cell apoptosis.amlodipine besylate has better effect on protecting cell apoptosis in mesenteric artery.