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Purpose: through the establishment of a rat model of atherosclerosis (AS), AS rat vascular reactivity observed olmesartan medoxomil and candesartan cilexetil, thus observed olmesartan medoxomil and candesartan cilexetil in endothelial protection role, and observe the NO and ET-1 content, a preliminary discussion of its mechanism of action. Methods: 40 normal male Wistar rats were randomly divided into four groups of A, B, C, D, A = normal group, B = high-fat group, C = candesartan cilexetil group and D = olmesartan medoxomil group A total of 8 weeks. Determination: (1) body weight and blood lipids in 0 weeks, two weeks, four weeks, six weeks and 8 weeks weighing; 0 weeks and 8 weeks were taken in each group of rats plasma lipid levels using the chemical method. ② Determination of rat vascular reactivity: 8 weeks to take the thoracic aortas preparation vascular ring, the vascular ring placed in a constant temperature of 37 ℃ vascular buffer isolated organ perfusion bath in a concentration of 10-6mol / L under the pre-contraction of norepinephrine (NE), the group of vascular rings of different concentrations of (10-9,10-8,10-7,10-6,10-5 mol / L) of acetylcholine (Ach) and denitrification were measured ordinary sodium (SNP) relaxation response, the dose - response curve, the maximum relaxation response (Emax) and cause maximum relaxation response to drug concentration (IC50) half to said vascular reactivity. ③ nitric oxide (NO) and endothelin -1 (ET-1) Determination: 0 weeks and 8 weeks, respectively collected plasma NO Determination Chemoenzymatic ET-1 Determination by radioimmunoassay. Results: ① olmesartan medoxomil impact on the AS rats body weight, lipid levels: 0 weeks, similar to the experimental rats body weight, blood lipid levels, no significant difference in sex (P gt; 0.05); 8 weekends, AS rat body weight, blood lipid levels significantly higher than in group A (P lt; 0.01), olmesartan medoxomil and candesartan cilexetil intervention does not affect the AS rats body mass, blood lipid level (P gt; 0.05). (2) the olmesartan medoxomil AS rat vascular reactivity: the relaxation response to different concentrations of SNP among the groups showed no significant differences (P gt; 0.05). The relaxation response to different concentrations of acetylcholine Ach, the dose-response curve AS rats compared with group A was significantly non-parallel to the left, Emax and IC50 group A compared with statistical significance (P lt; 0.01); C, D group than in group B, dose-response curves of non-parallel shift right, C group Emax 59.684 2.425% IC50 (9.711 ± 0.992) × 10-8 mol / L, D group Emax to 63.629 ± 2.165% (6.743 ± 0.564) × 10 IC50 -8mol / L, compared with group B, there is a significant difference (P lt; 0.01), and the comparison between the D and C groups, the difference was statistically significant (P lt; 0.05). ③ olmesartan medoxomil AS serum NO, ET-1 content: 0 weeks, serum NO, ET-1 content is insignificant, no statistical significance (P gt; 0.05); 8 weeks A group of rats NO content as 36.987 ± 3.051 umol / L, ET-1 content was 31.966 ± 3.523pg/ml, and AS rats were significantly different (P lt; 0.01), C, D serum NO, the ET- 1 content is statistically significant (P lt; 0.01) than in group B and Group D NO content was 29.94 ± 3.807 umol / L higher than group C (P lt; 0.05), ET-1 levels to 58.261 ± 5.137pg / ml, lower than that in group C (P lt; 0.05). Conclusion: ① AS rats significantly reduced endothelium-dependent relaxation, does not affect the endothelium-dependent relaxation. 2 olmesartan medoxomil and candesartan cilexetil may improve the AS rat endothelium-dependent relaxation response, and the the olmesartan medoxomil stronger candesartan cilexetil. ③ olmesartan medoxomil improve the AS rats vasodilation may be related to the increase in NO and lower ET-1 levels. Objective: This experimental atherosclerosis (AS), serum high sensitivity C-reactive protein (hs-CRP) determination of the content and AS rat aortic CD40 expression, observe the anti-inflammatory effects of olmesartan medoxomil AS rats , and further compare different anti-inflammatory effect of olmesartan medoxomil and candesartan cilexetil AS rats. Methods: 40 male Wistar rats were randomly divided into A normal group, high-fat group B, C candesartan cilexetil group D olmesartan medoxomil four groups. The AS model copy B, C, D C and D respectively while giving candesartan cilexetil and olmesartan medoxomil intervention. ① Determination of serum hs-CRP: 0 weeks and 8 weeks, respectively collected rat plasma 2ml, the collection of plasma centrifugation, the supernatant was measured by enzyme-linked immunosorbent assay (ELISA), serum hs-CRP content, comparing observed 0 weeks and 8 weeks in each group, serum hs-CRP content ② weekend of August, thoracotomy and rapid separation of the thoracic aorta - abdominal aortic CD40 expression in aortic tissue was measured as a semi-quantitative RT-PCR, the rats were anesthetized with UV detector photographed and observed GADPH internal reference to calculate the relative expression levels of CD40 in the aortic tissue groups were compared aortic CD40 expression. Results: (1) 0 weeks, A, B, C, D four groups of serum hs-CRP content similarity, between the groups compare without significantly with difference (P gt; 0.05); 8 weekend, the AS serum hs-CRP content was significantly high in normal rats (P lt; 0.01), the two-drug group with the high-fat group compared serum hs-CRP were significantly decreased (P lt; 0.01), and Group D olmesartan medoxomil intervention AS rats compared with C The ester group hs-CRP group candesartan content is low, there is a statistically significant (P lt; 0.01). The ② AS rat aortic CD40 expression was significantly higher than the control group (P lt; 0.01), the AS rats olmesartan medoxomil and candesartan cilexetil intervention, aortic CD40 expression decreased high-fat group than in group B (P lt; 0.01), compared to D group C and group D group CD40 expression below the C group, and a statistically significant (P lt; 0.01). Conclusion: (1) the AS rat serum inflammatory substances hs-CRP levels increased, high expression of CD40 and aortic tissue. The ② olmesartan medoxomil and candesartan cilexetil to reduce the content of AS serum hs-CRP, lower aortic CD40 expression. Olmesartan medoxomil and candesartan cilexetil the AS rats have anti-inflammatory effects. ③ with olmesartan medoxomil interventions the AS rat serum hs-CRP levels and aortic CD40 expression compared candesartan cilexetil reduce olmesartan medoxomil on the AS rats have a stronger anti-inflammatory effect.
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