Study On The Effect And Antioxidant Mechanism Of Tianhuangpian On Intimal Hyperplasia After Vascular Endothelial Injury

ObjectiveCardiovascular disease is very harmful to people' s physical and mental health,intimal hyperplasia with the occurrence and development of cardiovascular disease,is an important pathological basis.Endothelial cell is an important barrier to blood vessel,the intimal hyperplasia is an important pathological basis for cardiovascular disease.Prevention and treatment of intimal hyperplasia has become a hot and difficult point in the treatment of cardiovascular disease.Tianhuangpian(THP)is Professor Guo Jiao based on years of clinical experience summed up the prescription medicine,which has the efficacy of reducing phlegm and removing blood stasis.In this study,we established the rabbit model of intimal hyperplasia after vascular endothelial injury,to explore the effect and the antioxidative effect of THP on intimal hyperplasia,and to provide a new way and ideas for clinical treatment.Methods28 male rabbits aged 3-4 months old were randomly divided into control group(n=7)and operation group(n=21)after feeding for a period of up to 1 weeks.Control group fed with normal diet for 8 weeks did not undergo any operation;In the operation group,the abdominal aorta was injured by digital subtraction X ray,and then the rats were fed with high fat diet for 4 weeks,and second times balloon injury to establish intimal hyperplasia model,then were randomly divided into model group,THP group and atorvastatin group,7 rats in each group,after 4 weeks of administration of drug,all rabbits were killed.1.The MLD%and MLA%of each group was analyzed by using the instrument of angiography machine;Pathological examination of abdominal aorta was performed,and the intimal thickness and the ratio of intima to media thickness were calculated.2.Western blotting was used to detect the expression of NOX1,NOX4,eNOS,iNOS.3.ET-1,OX-LDL,LOX-1,PECAM-1,VEGF in the blood were detected by ELASA.4.Automatic biochemical analyzer was used to detect GLU,TG,TC,LDL,HDL in the blood.The visible light detection of CAT activity,determination of MDA by thiobarbituric acid method,determination of GHS-Px activity by DTNB quantitative method,using xanthine oxidase method to detect the activity of SOD,NO in the blood was measured with nitrate reductase method.Results1.Compared with the first angiography,the%MLD,%MLA of the second angiography in the model group was significantly higher(P<0.05),and the%MLD,%MLA of the third contrast enhanced(P<0.05).Compared with the control group,the intima thickness and intima/media thickness of the model group were significantly increased(P<0.05).In the model group,there was obvious intimal hyperplasia.2.After administration,compared with the control group,the%MLD,%M LA,the intima thickness,the intima/media thickness were all increased in the model group(P<0.05).Pathological observation showed that there was no thickening in the control group,the endothelial cells were arranged in order and no inflammatory cells invaded.The intima of model group was significantly thickened,a large number of inflammatory cells invaded,and smooth muscle cells migrated to the intima.Compared with the model group,the intimal thickening of THP group and atorvastatin group were significantly reduced,the intima was smooth,the inflammatory cells were significantly reduced,and the smooth muscle migration was significantly reduced.Compared with the model group,the intima thickness,the intima/media thickness,%MLD and%MLA significantly reduced in the THP group and atorvastatin group(P<0.05).There was no significant difference between the THP group and the atorvastatin group.THP and atorvastatin can improve abdominal aortic intimal hyperplasia.3.Compared with the control group,The GLU,TC,TG,HDL,LDL in the blood increased significantly in the model group(P<0.05).Compared with the model group,the level of GLU,TC,TG,LDL in the blood could reduce in the atorvastatin group(P<0.05),but it was no significant effect on HDL(P>0.05).THP could significantly increase the level of HDL and reduce TC,LDL in the blood(P<0.05),but had no significant effect on TG,GLU(P>0.05).Both THP and atorvastatin can decrease the level of blood lipid in rabbit model of intimal hyperplasia after vascular endothelial injury.4.The model group SOD,CAT,GHS-Px in the blood was significantly lower than that of the control group(P<0.05),and MDA,NOX1,NOX4 was higher than that of the control group(P<0.05).Compared to the model group,the activity of SOD,CAT,GHS-Px in the blood increased,but the MDA,NOX1,NOX4 reduced in the THP group and atorvastatin group(P<0.05),to improve the oxidative stress state of blood vessels.The expression of MDA and NOX1 were lower in THP group than those in atorvastatin group,and the activity of CAT is higher(P<0.05).5.Compared to the control group,the endothelial function of the model group was impaired,the NO secreted by endothelial cells decreased,ET-1 increased,and the expression of eNOS in abdominal aorta decreased significa ntly(P<0.05).Compared with the model group,NO,eNOS increased,and ET-1 decreased in THP group and atorvastatin group(P<0.05),to improve of vascular endothelial function.6.Compared with the control group,the model group OX-LDL,PECAM1,VEGF increased significantly in the blood(P<0.05).THP can reduce the expression of VEGF(P<0.05),but it has no obvious effect on OX-LDL,LOX-1 and PECAM1.Conclusions1.The model of intimal hyperplasia after vascular endothelial injury was successfully established with obvious high glucose and hyperlipidemia,and the oxidation state of the model was enhanced and the endothelial function was impaired.2.THP can inhibit intimal hyperplasia after vascular endothelial injury,which may play a role in reducing blood lipid level,improving the oxidative stress of blood vessels,promoting the formation of NO and further improving the vascular endothelial function,to achieve the role of reducing phlegm and removing blood stasis,improving intimal hyperplasia of blood vessel.