Research On The Prescription Of Clearing Away Heat, Removing Phlegm And Promoting Blood Circulation By Regulating The Ubiquitin-proteasome Pathway To Inhibit The Progression Of Atherosclerosi

Obsjective:To observe the effect of Qingre Quyu Granule(QRQY)on ApoE gene knockout mice in atherosclerosis and to discuss whether its mechanism is associated with the ubiquitin proteasome pathway.Methods:Apo E knockout mice were randomly divided into high fat diet group(n=60)and QRQY group(n=60).QRQY group again divided randomly into three sub-groups of large,medium and small doses.They were respectively given normal saline(10 mg/kg·d)and QRQY(60mg/kg-d,180mg/kg-d,540mg/kg-d).Each group was further divided into two sub-groups(n=20)for the treatment course of 5 weeks and 22 weeks to valuate the effect of QRQY of large,medium and small doses on aortic plaque morphology subsequently.According to the results of the assessment,selecting the optimum drug dose group and comparing to the control group.Observing the aortic plaque morphology change and the expression of the NF kappa B p65,ICAM-1,MMP-9,CD40L,ubiquitin,and proteasome.Results:QRQY medium dose group was better in inhibition of atherosclerosis than high dose group and small dose group.Compared with high dose group,QRQY medium dose group significantly decreased the content of lipid core plaques(P<0.01),inhibited the expression of ubiquitin proteasome P65 subunit,and NF-KB(P<0.01).After 5 weeks,ICAM-1 expression in QRQY medium dose group were obviously lower than that of the control group(P<0.01).After 22 weeks,the expression of MMP9 and CD40L were significantly lower(P<0.01)in QRQY medium dose group compared with the control group.In this study,we explored the relationship between the effect of QRQY on the stability of vulnerable plaque in atherosclerosis and the ubiquitin proteasome pathway.What's more,the effect of QRQY was not a simple sense of the dose dependent relationship.Conclusion:Qingre Quyu granule group could significantly reduce the expression of plaque inflammatory factors,reduce lipid core content and inhibit atherosclerosis progression.The mechanism of QRQY in inhibiting atherosclerosis progression was related with ubiquitin proteasome pathway(UPP).Ubiquitin-proteasome path may be a new target point of traditional Chinese medicine for stabilizing vulnerable plaque.