Effects Of Ad-HGF Via Intrathecal Injection On The Expression Of Inflammatory Factors In Brain Tissue Of Atherosclerotic Rats

BackgroundCerebral atherosclerosis is the rank main cause of stroke,especially multiple stenosis and diffuse stenosis.How to reconstruct the effective blood to improvl the ischemia caused by cerebral atherosclerosis,is a difficult clinical problem.Hepatocyte growth factor is a hepatogenic factor.It plays an important role in promoting angiogenesis.Adenovirus vector encoding HGF gene（Ad-HGF）is a new genetreatment method.It can relieve cerebral ischemia.In this study,we established the rat model of aged atherosclerosis.Then we injected Ad-HGF into subarachnoid space to observe the pathological changes and the inflammatory reactions in brain tissue,NF-κB p65、IL-10、IL-6 and TNF-α.We can verify the Ad-HGF,to provide evidence for the application of Ad-HGF in cerebral atherosclerosis.ObjectiveCerebral is a particularity structure,we intend to observe the pathological and inflammatory factors changes in the rats after Ad-HGF,for example NF-κB p65、IL-10、IL-6 and TNF-α.We can investigate the effect of Ad-HGF on the aged atherosclerotic rats.Methods1.Model:Renal hypertension combined with high fat feeding to establish aged atherosclerosis model^[47].2.Animas grouping:Animals were divided into the normal control group and the aged atherosclerotic group andAd-HGF 10d group,Ad-HGF 20d group and Ad-HGF 30d group.3.Inflammatory factors expressiont:After the aged atherosclerosis model was made,we can get out the brains of each groups and investigate the expression of inflammatory factors by quantitative real-time PCR、immunohistochemistry and ELISA.Results1.Blood pressure,blood lipids and HE staining:Compared with the normal control group,the blood pressure and blood lipid levels of the model group were significantly higher（P<0.05）;The internal carotid artery HE staining of the model group show that structure disorder and atherosclerotic plaque.2.Immunohistochemical results:A small amount of NF-κB p65、IL-10、IL-6 and TNF-αpositive cells were detected in the control group.While,In aged atherosclerosis group,the expression of NF-κB p65、IL-10、IL-6、TNF-αincreased.The expression of NF-κB p65、IL-6 and TNF-αwere decreased while IL-10 was increased after Ad-HGF.There was a significant difference of IL-10 in the Ad-HGF 10d group（P<0.05）,and the positive expression of IL-10 reached the peak in the Ad-HGF 20d group.We observed that the positive expression of IL-10 began to decrease in the Ad-HGF 20d group.It was found that the expression of NF-κB p65 in the aged atherosclerosis group was increased,then decreased after Ad-HGF.There was a decreasing trend in the Ad-HGF 10d and Ad-HGF 20d group（P<0.05）.However,there was no significant difference in Ad-HGF20d group and Ad-HGF 30d group,which may be related to the time of action of Ad-HGF.3.qRT-PCR results:Compared with the aged atherosclerosis group,the expression of IL-10 increased and NF-κB p65 decreased in Ad-HGF 10d group and Ad-HGF 20d group.The results showed that Ad-HGF increased the expression of anti-inflammatory factor IL-10 and played an important role in alleviating the inflammatory reaction of brain tissue（P<0.05）.4.ELISA results:The expression of IL-6 and TNF-αin aged atherosclerosis group were increased,but the expression of IL-6 and TNF-αwere decreased after Ad-HGF（P<0.05）.Conclusions1.Exogenous Ad-HGF can regulate the levels of NF-κB p65、IL-10、IL-6 and TNF-α,which provides a basic experimental basis for the treatment of Ad-HGF in cerebrovascular diseases.2.The effect of Ad-HGF reached its peak in about 20 days,which provided the basis for the R&D of Ad-HGF in the treatment of CAS.