The Mechanism Of Effect Of Yiqi Huoxue Recipe On Th17/Treg Balance In The Rabbit Model Of Atherosclerosis Vulnerable Plaque

Objectives:To observe the effect of Yiqi Huoxue Recipe on the Th17/Treg balance and the expression of related transcription factors and cytokines in vulnerable atherosclerosis plaque model,and to explore the possible mechanism.Methods:According to the random and controlled method,30 healthy male New Zealand Rabbits were divided into two groups,group A(n=6),model group(n=24).Group A were fed with normal diet.Model group were fed with high-fat diet,at the end of the 4th week,model group were treated with balloon injury of abdominal aorta and injection of bovine serum albumin from ear edge vein.until 12th week,underwent pharmacologic triggering with injection Chinese Russell’s viper venom and histamine.Survival experimental rabbits were randomly divided into group B(n=5,without drug intervention),group C(n=5,treated by simvastatin),group D1(n=5,treated by Yiqi Huoxue Recipe high dose)and group D2(n=5,treated by Yiqi Huoxue Recipe conventional dose).From the 13th week,group C,D1 and D2 were intervened with simvastatin capsule(0.83g·kg-1·d-1),high dose of Huoxue Yiqi recipe(4g·kg-1·d-1)and routine dose of Huoxue Yiqi recipe(2g·kg-1·d-1),while group B without drug intervention.Fasting blood samples were collected at the beginning of the experiment,after modeling and after treatment.The levels of transcription factors ROR-yt,Foxp3 and cytokines IL-10,IL-23,IL-17,IL-35 and TGF-β were detected by enzyme-linked immunosorbent assay(ELISA).Real time PCR was used to detect the expression of ROR-yt and Foxp3 mRNA.The morphology of aortic plaque was observed by ordinary pathology.Results:1.Rabbits were fed by high-fat,injuryed by balloon-induced abdominal aorta,then immune injury induced by intravenous injection of bovine serum albumin,finally triggered by Chinese spotted viper venom and histamine to build the vulnerable plaque animal model.2.In the vulnerable plaque animal model,the levels of IL-17,IL-23 and ROR-yt increased,while the levels of IL-10,IL-35,TGF-β and Foxp3 decreased.IL-17 was positively correlated with IL-23 and ROR-yt,and negatively correlated with IL-35;while IL-35 was positively correlated with the decrease of TGF-β and Foxp3;ROR-yt was negatively correlated with Foxp3.The differences were statistically significant(P<0.05).3.Compared with Group B,the serum levels of I-17,IL-23 and ROR-yt in Group C,D1 and D2 were lower(P<0.05);the serum levels of IL-10,IL-35,TGF-β and Foxp3 Group C,D1 and D2 were higher(P<0.05).4.Compared with Group B,the expression of Foxp3 mRNA in group C,D1 and D2 was significantly increased,the expression of ROR-yt was significantly decreased,and the ratio of Foxp3/ROR-yt was increased(P<0.05).Conclusion:Yiqi Huoxue Recipe can delay the progression of plaque and stabilize the vulnerable plaques by regulating the balance of Th17/Treg.