Based On The Pathogenic Theory Of Poisonous Pathogens, The Research On The Effect Of Clearing Away Heat And Detoxification In Regulating Macrophage Polarization And Anti-AS

Purpose:Objective to observe the effect of"Danlou Tablet Plus gardenia and Forsythia suspensa"on blood lipid level,morphological changes and macrophage polarization related indicators in ApoE^-/-mice,and to explore the effect and mechanism of"Qingre Jiedu method"in regulating macrophage polarization against atherosclerosis,so as to provide scientific experimental basis for clinical application.Material and method:Forty SPF grade healthy ApoE^-/-mice were randomly divided into 5 groups:control group,model group,Danlou tablet group,Danlou Tablet Plus gardenia,Forsythia suspensa group and simvastatin group,with 8 mice in each group.The mice in the control group were fed with normal diet every day.The mice in the model group,Danlou tablet group,Danlou Tablet Plus gardenia,Forsythia suspensa group and simvastatin group were fed with high-fat diet every day.After 8 weeks of feeding,the model group,Danlou tablet group,Danlou Tablet Plus gardenia,forsythia group and simvastatin Group continued to be fed with high-fat diet,and drug intervention was carried out at the same time.The dosage was converted according to the equivalent dose conversion coefficient.The pharmacokinetic concentration of Danlou tablet group was 0.03g/ml and 0.2ml,and the pharmacokinetic concentration of Danlou Tablet Plus gardenia and forsythia group was 0.03g/ml+0.06g/ml+0.08g/ml and0.2ml respectively The concentration of simvastatin group was 0.26 mg/ml,once a night.The mice in the control group and the model group were given the same volume of normal saline every day.After 4 weeks of treatment,the levels of TC,TG,LDL and HDL in serum of ApoE^-/-mice were detected;the morphological changes of atherosclerosis in aortic tissue of ApoE^-/-mice in each group were detected by hematoxylin eosin（he）staining method;Western blot was used to detect the changes of atherosclerosis in aortic tissue of ApoE^-/-mice The protein expressions of p-STAT1,STAT1,p-STAT6,STAT6,iNOS and TGF-βin the aorta of mice were detected by blot,and the mRNA expressions of IL-1β,MMP-2,MMP-9,IL-10,IL-4 and Arg-1 were detected by qRT-PCR.Results:1.The results of blood lipid test showed that:compared with the control group,the levels of TC,TG and LDL in the model group were significantly increased（P<0.05）;the level of HDL was significantly decreased（P<0.05）;compared with the model group,the levels of TC,TG and LDL in the Danlou tablet group,Danlou Tablet Plus gardenia,Forsythia suspensa group and simvastatin group were significantly decreased（P<0.05）;the level of HDL was significantly increased（P<0.05）.2.HE staining results showed that compared with the control group,inflammatory cells infiltration and mast cells increased in the model group,forming foam like cells and obvious plaque area.Compared with the model group,Dan Lou tablets,Dan Lou tablets plus gardenia,Forsythia suspense group and simvastatin The plaque area in the statin group was significantly reduced.3.Western The protein expression of p-STAT1,STAT1,p-STAT6,STAT6,iNOS and TGF-βin the aorta of mice were detected by blot.The results showed that compared with the control group,the protein expression levels of p-STAT1/STAT1 and iNOS in the aorta of mice in the model group were significantly increased（P<0.05）;compared with the model group,the protein expression levels of p-STAT1/STAT1 and iNOS in the Danlou tablet group,Danlou Tablet Plus Gardenia jasminoides Ellis,Forsythia suspensa group and simvastatin group were significantly increased Compared with the control group,the protein expression levels of p-STAT6/STAT6 and TGF-βin the model group were significantly decreased（P<0.05）;compared with the model group,the protein expression levels of p-STAT6/STAT6 and TGF-βin the Danlou tablet group,Danlou Tablet Plus gardenia,Forsythia suspensa group and simvastatin group were significantly increased（P<0.05）.4.qRT-PCR was used to detect the mRNA expression levels of IL-1β,MMP-2,MMP-9,IL-10,IL-4 and Arg-1 in the aorta of mice.The results showed that compared with the control group,the mRNA expression levels of IL-1β,MMP-2 and MMP-9 in the model group were significantly increased（P<0.05）;compared with the model group,the mRNA expression levels of IL-1β,MMP-2 and MMP-9 in the Danlou tablet group,Danlou Tablet Plus Gardenia jasminoides Ellis,Forsythia suspensa group and simvastatin group were significantly increased（P<0.05）Compared with the control group,the mRNA expression levels of IL-10,IL-4 and Arg-1 in the model group were significantly decreased（P<0.05）;compared with the model group,the mRNA expression levels of IL-10,IL-4 and Arg-1 in the Danlou tablet group,Danlou Tablet Plus gardenia,Forsythia suspensa group and simvastatin group were significantly increased（P<0.05）.Conclusion:1.High fat diet can cause lipid metabolism disorder and atherosclerosis in aope^-/-mice.2.Macrophage polarization is involved in the process of atherosclerosis.3.The mechanism of"Qingre Jiedu method"in improving aortal injury of ApoE^-/-mice may be related to the regulation of macrophage M1 polarization to M2 polarization.