| Objective:To investigate whether atorvastain dose-dependently affects intima, tunica media, NADPH oxidase, superoxide anion in mice with vascular injuryMethods:Polyethylene tube was placed loosely around the femoral artery of male C57BL/6 mice, was vascular injury model. Randomly divided into five groups:atorvastatin treatment groups:low dose group (2.5mg/kg.d), high dose group (5mg/kg.d), surgical control group, normal control group, sham operation group. By oral administration. When the 7 and 14-day,the mouse were anesthetized, harvesting the femoral artery of the five group. HE staining and measured intimal and medial area by the NIH analysis software.RT-PCR detection of p22phox, p47phox and rac-1 mRNA expression level. Application Chemiluminescence determination of superoxide anion content on the femoral artery. Each group 16 mouse were randomly selected to test blood lipids and liver function before and after experiment. Normal control group and sham operation group only prove successful model and excluded surgical interference.Results:①7-day period, there were no intimal thickening in sham operation group, normal control group(intimal area:0μm2); the intimal area of surgical control group compared with other groups was significant difference (p<0.05), the maximum degree of intimal thickening (269.95±2.41μm2); low dose group (160.17±2.44μm2) and high dose group (160.17±2.39μm2) compared with the surgical control group, significantly reduced intimal thickening (p<0.05), between two treatment groups showed no significant difference (p> 0.05); each group there was no thickening of the tunica media (p> 0.05). 14-day period, the sham operation group, normal control group, no intimal thickening (intimal area:0μm2); the surgical control group intimal area compared with other groups was significant difference (p<0.05), maximum degree of intimal thickening (370.21±2.42μm2); low dose group (199.86±2.48μm2) and high dose group (201.51±3.11μm2)compared with surgical control group, significantly reduced intimal thickening (p <0.05), between the two treatment groups was no significant difference (p> 0.05); each group there was no thickening of the membrane performance (p> 0.05).14-day surgical control group (370.21±2.42μm2) compared with 7-day surgical control group (269.95±2.41μm2)was a high degree of intimal thickening (p<0.05),14-day treatment group than 7-day treatment group intimal thickening rate slowed down significantly.②p22phox, p47phox and rac-1 mRNA relative expression,7-day period:the normal control group (0.1450±0.037,0.1350±0.034,0.1363±0.030) and sham operation group (0.1325±0.033,0.1338±0.032.0.1350±0.033) were the lowest, low-dose group (0.5300±0.038,0.5238±0.037,0.5450±0.037) and high dose group (0.5225±0.028,0.5163±0.030. 0.5350±0.040)were higher, expression of the surgery control group (0.7475±0.036,0.7438±0.032,0.7400±0.020) was the highest, the expression of two treatment groups showed no significant difference (p> 0.05); 14-day period:the normal control group (0.1313±0.031,0.1200±0.025,0.1388±0.036) and sham operation group (0.1350±0.024,0.1350±0.024,0.1425±0.031) were the lowest, low-dose group (0.3450±0.032,0.3413±0.029,0.3350±0.033) and high dose group (0.3500±0.035,0.3363±0.032,0.3325±0.029) were higher, surgical control group (0.8875±0.030,0.8788±0.020,0.9138±0.015)was the highest, expression of the two treatment groups showed no significant difference (p> 0.05); 14-day surgical control group (0.8875±0.030,0.8788±0.020,0.9138±0.015) compared with 7-day surgical control group (0.7475±0.036.0.7438±0.032,0.7400±0.020) significantly increased expression,14-day treatment group compared with7-day treatment group, the expression was significantly lower.±O2-content of femoral atery wall,7-day period, the normal control group (1726.09±110.96 nmol/(mg·min)) and the sham operation group (1820.10±118.50 nmol/(mg·min)) were the lowest, low dose treatment group (3680.07±302.18 nmol/(mg·min)) and high dose treatment group (3492.74±248.02 nmol/(mg·min)) were higher, surgical control group (5743.57±120.12 nmol/(mg·min)) was the highest, in the two treatment groups showed no significant difference (p> 0.05); 14-day period:the normal control group (1582.37±248.55 nmol/(mg·min)) and sham operation group (1557.50±188.72 nmol/ (mg·min)) were the lowest, low-dose treatment group (2454.09±224.82 nmol/(mg min)) and high dose treatment group (2378.05±262.89 nmol/(mg·min))were higher, surgical control group (7695.14±247.83 nmol/(mg·min))was the highest, in the two treatment groups showed no significant difference (p> 0.05); 14-day surgical control group (7695.14±247.83 nmol/(mg·min)) compared with 7-day surgical control group (5743.57±120.12 nmol/(mg·min)) were significantly higher,14-day treatment group compared with the 7-day treatment group were significantly reduced. Experiments before and after each group the lipids and the liver functions were no significant difference (p> 0.05), blood lipids and liver functions between groups were no significant difference (p> 0.05).④By Spearman correlation analysis, can be found p47phoxmRNA,p22phoxmRNA, raclmRNA the relative expression and O2- levels was a positive correlation between the correlation coefficient r1=0.918,r2=0.907, r3=0.920, P<0.05, statistically significant.Condusions:Short-term application of atorvastatin could inhibit the main subunit p22phox, p47phox, rac-1 mRNA expression in NADPH oxidase, thereby reducing the production of superoxide anion, play a role in anti-oxidation, and slow down the rate of injury intimal thickening, to suppress vascular remodeling purposes. This effect is a part of antioxidant mechanisms, this effect independent of their lipid-lowering effect, short-term time-dependent manner, but does not increase the dose further enhanced the effect. |
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