Effect Of Qinghua Huatan Huoxue Recipe On Susceptible Plaque Of Aorta And Its Relationship With Proteasome Pathway In ApoE Knockout Mice

Atherosclerosis (AS) is the critical pathological basis of cardiovascular disease. The related incidence has been rising gradually in recent years. Many researches found that Vulnerable plaque which leads to Plaque rupture and Secondary thrombus is one of the main reasons of such diseases like Acute Coronary Syndrome and acute cerebral infarction. In 1999, beyond the knowledge of AS, Ross proposed an idea that ASwas a kind of inflammatory diseases based on the Endothelial injury theory, which has been widely accepted. A lot of evidences indicate that AS plaque inflammation was closely related to plaque rupture, the more active of inflammation, the more unstable of plaque. Hence, various kinds of inflammatory factors involved in AS vulnerable plaque lesions drawn attentions in recent researches. The relationship between Oxidative stress and atherosclerosis progression is intimate. The Oxygen free radicals produced by Oxidative stress have complex oxidation reaction with protein, lipid, and nucleic acid, inducing damages such as endothelial cell injury, smooth muscle cell proliferation, proliferation and extracellular matrix degradation. This damages have critical influence on the injury of blood vessel and the formation of the atherosclerotic plaque. Our past research shows that Qingre Huatan Huoxue Fang is able to stabilize the vulnerable plaque, however the specific mechanism needs to be further analyzed. This experiment aims to reveal this mechanism on observing the influence of Qingre Huatan Huoxue Fang on the atherosclerotic vulnerable plaque of ApoE gene knocking out mice.Objective:To investigate theeffect ofQingre Huatan Huoxue Formula (QHHF)onstabilizingvulnerble plaguesand the effect of ubiquitin-proteasome systemon aorta artery in the of Apo E knockout miceMethods:Eighty male Apo E deficient mice were fed with high-fat diet,beginning at eight weeks of age. They were randomly divided into control group, bortezomib group, bortezomib+QHHF group and QHHF group (n= 20,each).At the 13-week old, they were given normal saline 10mg/kg/d, bortezomib3.0mg/kg/d, bortezomib3.0mg/kg/d+QHHF180mg/kg/d or QHHF180mg/kg/d for another 17 weeks. At the end of experiment we evaluated theaorta artery.The level of superoxide anion, the expression of anti-mice Monocyte/macrophages 2(MOMA-2) monoclonal antibody,nuclearfactor-kappa B(NF-KB)/p65 and CD40L were determined by fluorescence or immunofluorescence in all animals.Results:The levels of superoxide anion.the MOMA-2, NF-κB/p65 in bortezomib+QHHF group and bortezomib group both have no difference.but the lipid content of plaques decreased. The expression of superoxide anion,the MOMA-2.CD40L, NF-KB/p65 and lipid content of plaues in QHHF group were significantly lower than that in the other groups.Conclusion:The QHHF Granule can inhibit the expression of inflammatory factor in aorta artery,the mechanism is partly related to inhibiting the ubiquitin-proteasome system.Proteasome may be a newtarget spot of Chinese traditional medicine.