Intervention Of P22phox - Mediated Oxidative Stress In SHR Vascular Remodeling

Objective:To observe the effect of Fufang Gouteng tablets of different doses on blood pressure,morphological changes of thoracic aortic tissue, the expression of p22phox protein and plasma IL-10concentration of SHR,explore the effect of Fufang Gouteng tablets on blood pressure, vascular remodeling in SHR rats and the corresponding mechanism.Methods:508-weeks-old male SHR were randomly divided into5groups: model group, traditional Chinese medicine group of high,middle and low dose, positive control group, another10WKY in blank control group. The traditional Chinese medicine groups’rats were gavaged with Fufang Gouteng tablets and intragastric volume of high,middle and low dose were respectively2times,1times,0.5times as clinical equivalent weight.Positive control groups’were gavaged with irbesartan of clinical equivalent volume.Model groups’and blank control groups’were treated with equal volume of distilled water.All rats were intervened successively for4weeks. The tail artery pressure were measured2times a week before and every week after the intervention,gotting the average values into final datas.After the experiment, plasma were blooded in the abdominal aortas to test concentration of IL-10by ELISA. Thoracic aortic tissue samples were clipped to observe the morphology under HE staining,measure IMT, LD and IMT/LD of thoracic aortas by using computer aided imaging measurement system,detect expression of p22phox protein through immunohistochemistry.Results:Compared with model group, traditional Chinese medicine group of high and middle dose both lowered tail arterial pressure of SHR (P<0.05),which appeared dose-dependentbetween each other (P<0.05);As shown under HE dyeing at high magnification (X400times),thoracic aorta of model group’s rats arose vascular remodeling which displayed intima hyperplasia and smooth muscle cells disordered arrangement and migration toward to the under-intima,also IMT and IMT/LD of thoracic aorta increased significantly (P<0.01),compared with blank group;Traditional Chinese medicine group of high and middle dose showed milder vascular remodeling under a light microscope,lower IMT and IMT/LD compared with the model group (P<0.05); As same as they did about p22phox protein expression on the thoracic aortic (P<0.05),which also appeared dose-dependent (P<0.05); On the contrary, plasma IL-10concentration of traditional Chinese medicine group of high and middle dose both were higher than that of model group (P<0.05), which presented dose-dependent too (P<0.05).But the morphological and biological indicators above of Chinese medicine group of low dose did not improve compared with that of model group.Conclusion:(1)Fufang Gouteng tablets can lower blood pressure of SHR and reverse its vascular remodeling.(2)The probable mechanism of Fufang Gouteng tablets attenuating vascular remodeling of SHR is that it should increase the level of IL-10, downregulate p22phox expression and reduce its mediated vascular oxidative stress to alleviate the injury of vascular endothelial cells and hyperplasia,proliferation and migration of VSMC, thus reversing VR.