Study On The Effect And Mechanism Of Ursolic Acid Inhibited The Abdominal Aortic Aneurysm

Part ? Ursolic Acid Prevents Angiotensin ?-Induced Abdominal Aortic Aneurysm in Apolipoprotein E-Knockout MiceObjective:Abdominal aortic aneurysms(AAA)is a chronic disease where inflammation plays an important role.However,the specific signal pathway associated remains unclear.This study delved into the efficacy of ursolic acid(UA)on the pathogenesis of Ang ?-induced AAA in Apo E-/-mice and show the protective effect of UA on the formation of AAA.Methods: 38 male Apo E-/-mice at 8 weeks of age were randomly divided into control group(n=13),tap water group(n=13)and UA treatment group(n=12).All the mice were implanted with a mini-osmotic pump subcutaneously.The control group were intragastric gavaged with tap water containing 0.1% Tween 80 daily throughout the study starting one week before implantation of the pumps and were infused with 0.9% Na Cl.The tap water group were gavaged with tap water containing 0.1% Tween 80 and.infused with Ang ?.UA treatment group were intragstric gavaged with 100 mg/kg UA.and infused with Ang ?..After 28 days,mice were sacrificed.Immunohistochemistry and Western blot were utilized to explore the potential effect of UA on AAA.Results: Infusion of Ang ? prominently increased the incidence of AAA whereas intragastric gavage of UA decreased the incidence of Ang ?-induced AAA in mice.Immunohistochemistry showed expressions of ADAM17,phospho-STAT3(pSTAT3),MMP2,MMP9 and NF-?B were obviously elevated in tap water group.Western blot indicated that UA could decreased the over expression of ADAM17,phospho-STAT3 (pSTAT3),MMP2,MMP9 and NF-?B in aorta of mice induced with Ang ?.Conclusion: We demonstrated that the expressions of ADAM17 and pSTAT3 were elevated companied with the up-regulated down stream expressions of MMP2 and MMP9 and lead to the formation of AAA.UA ameliorated the severity of AAA and exhibited an inhibitory effect on the expression of pSTAT3 and ADAM17.UA might emerge as a promising agent contributing to the prevention or treatment of AAA.Part ? study on the effects and mechanisms of UA on cytokines-induced inflammatory response in VSMCsObjective: The formation of abdominal aortic aneurysm is closely related to the inflammatory response of vascular smooth muscle cells(VSMCs).Recent studies indicate that inflammatory signaling pathways are activated in abdominal aortic aneurysms and the expression of inflammatory markers increases.Ursolic acid(UA)is a natural anti-inflammatory compound.This study was to explore the effects of UA on cytokines-induced inflammatory response in VSMCs and the specific molecular mechanisms behind it.Methods: VSMCs were treated with an increasing dosage of UA or DMSO for 24 hours.MTT assay wound healing assay and colony formation assay were used to measure the cell viability,proliferation and migration of VSMCs.The expression of pSTAT3 level was detected by Western blot method.Ang ? and TNF-? with different concentrations of UA in VSMCs.And we further examined whether UA could inhibit Ang ? or TNF-?-induced ADAM17,pSTAT3 and the expression of MMPs in VSMCs.Results: MTT and colony formation assays and wound healing assays indicated that UA suppressed VSMCS proliferation and migration in a dose-dependent manner(p<0.01).Western blot showed that UA could inhabit the expression of pSTAT3,MMP2 and MMP9 in VSMCs.Ang ? and TNF-? could induce the expression of ADAM17,pSTAT3,MMP2 and MMP9 while UA could affect the increased expressions(P<0.01).Conclusion: The finding that UA could suppress VSMCs proliferation and migration in a dose-dependent manner indicated that UA could have potential anti-inflammatory function to VSMCs.The Western blot showed UA could affect the increased expression of ADAM17,pSTAT3,MMP2,and MMP9 induced by Ang ? and TNF-?.This suppressive effect of UA on ADAM17,pSTAT3 and MMPs might underlie the mechanisms that UA alleviated the inflammatory response.This study provided a basic evidence for the use of ursolic acid as an anti-inflammatory agent to suppress AAA.