摘要
目的在腹主动脉狭窄高血压大鼠模型上观察心肌肥厚的变化,并探讨其与多种细胞因子、基质金属蛋白酶、心肌细胞凋亡率、凋亡调控基因表达等多种因素之间的关系及血管紧张素转化酶抑制剂(ACEI)和血管紧张素受体拮抗剂(ARB)对心肌肥厚和各种影响因素的作用。方法双抗夹心ELISA法测定MMP-2、MMP-9和IL-6、IL-10;放免法检测TNF-α;流式细胞法测心肌细胞凋亡率和凋亡调控基因表达。结果腹主动脉狭窄6周后,大鼠左室重及室重/体重比值明显增加;同时多种细胞因子、基质金属蛋白酶、心肌细胞凋亡率、凋亡调控基因表达等均发生了相应的变化;ACEI和ARB对心肌肥厚和各种影响因素有较好的预防和治疗作用,且两药联用作用好于单独应用。结论心肌肥厚可能与多种因素有关;ACEI和ARB对预防和治疗心肌肥厚有一定的作用,且两药合用作用好于单独应用。
AIM: To explore the effect of the combination of ACEI and ARB on left ventricle in pressureoverloaded hypertrophy rats, and also the relationship between left ventricular hypertrophy (LVH) and cytokines, matrix metalloproteinases, apoptosis, and apoptosis genes. METHODS: IL-6, IL-10, MMP-2 and MMP-9 were evaluated by ELISA method. TNF-alpha was measured with radioimmunoassays. Flow cytometer was used to measure the apoptosis ratio and the expression of Fas, Bcl-2 and Bax. RESULTS: 6 weeks after abdominal aortic coarctation operation, the weight of the left ventricle (0.983 ± 0.316 g) and heart weight/body weight (0.382 ± 0.154) were significantly increased in control group compared with the sham operated group. And also IL-6 (208.71 ± 84.51 pg·ml^-1 ), TNF-α (1.983 ± 0.842 ng·ml^-1 ), MMP-2 (74.63 ± 37.62), MMP-9 (57.74±25.61), apoptosis ratio (8.47 ± 4.18) and apoptosis genes ( fas , bax , bcl- 2, bcl- 2/bax) expression were increased, but IL-10 (86.23 ± 40.13 pg·ml^-1 ) was deereased eompared with sham operated group. The 3 groups with drugs (CP, LT, CP+ LT) decreased the increasing weight of LV and ventrieular weight/body weight and inhibited the changes of influencing factors (IL-6, IL-10, TNF-α, MMP-2, MMP-9, apoptosis ratio and apoptosis genes expression), especially in the group of combination of 2 drugs. CONCLUSION: LVH might be related with many influencing factors. ACEI and ARB may have the positive importance in the treatment and prevention of LVH.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2006年第10期1133-1136,共4页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
2003年山东省科技攻关计划项目(№032050114)