Effects Of Astragalus Polysaccharides On Angiotensin ?-induced Hypertension, Vascular And Kidney Injury In Mice

Astragalus membranaceus,also called Radix Astragali,is a leguminous perennial herbaceous plant,well known as a traditional Chinese medicine with various biological effects(nourishing effect,hepatoprotection effect,diuretic action and phlegm effect)and pharmacological activities(immunomodulatory effect,hypoglycemic effect,anti-inflammatory effect,antioxidant effect and anti-virus effect).Astragalus membranaceus has been used as a traditional Chinese medicine for treatment of various kinds of diseases for more than two thousand years,and recorded in the Shennong Pharmacopoeia of the Han Dynasty.The root of Astragalus membranaceus has been proved to contain Astragalus saponins(three terpene saponins),flavonoids,astragalus polysaccharides and some trace elements.It has been proved that Astragalus membranaceus contains more than 200 components,such as flavonoids,saponins,polysaccharides and amino acids,and many biological activities of these components have been demonstrated.Among the active components,astragalus saponins(three terpenoid saponins),isoflavones and astragalus polysaccharides are more studied than others.Many active components,including astragaloside,astragaloside and astragalus polysaccharides,have certain effects on diabetes,atherosclerosis,liver fibrosis,and so on.Recent animal studies and clinical observations have found that Astragalus membranaceus presents anti-hypertensive effect.However,what types of the active components of Astragalus membranaceus,including astragalus polysaccharides(APS)and flavonoids,have a certain curative effect on hypertension,as well as its specific molecular mechanism needs to be explored.The purpose of this thesis was to explore the protective effect of astragalus polysaccharide on angiotensin II induced hypertension in mice by investigating the effects of exogenous administration of astragalus polysaccharides on blood pressure and vessel and kidney injury,thus to reveal pharmacological and pharmacodynamic effects and molecular mechanism of astragalus polysaccharides on angiotensin II induced hypertension in mice.The results were presents as following:1.APS inhibited AngII induced hypertension and vascular and renal injury: Treatment with APS reduced Ang II induced hypertension in mice as companied with lowing both systolic blood pressure and diastolic blood pressure;significantly inhibited the increase of vascular thickness,collagen accumulation,abnormal expression of vascular inflammatory factors and fibrotic factors,and ROS production;APS significantly inhibited renal ROS production,collagen accumulation,abnormal expression of inflammatory factors and fibrotic factors in mice;and increased the expression of FGF21 and adiponectin in mice.2.AAV-FGF21 alleviated AngII induced hypertension and vascular and renal damage: AAV mediated FGF21 overpression inhibited Ang II induced hypertension in mice,and decreased amplitude of vascular thickness increase,aortic ROS production,collagen accumulation and abnormal expression of inflammatory factors and fibrotic factors in blood vessels of Ang II treated mice.AAV-FGF21 administration significantly reduced renal ROS production,collagen accumulation and abnormal expression of inflammatory factors and fibrotic factors in mice.3.AAV-APN attenuated Ang II induced vascular and renal injury: AAV-APN had no obvious inhibitory effect on blood pressure of Ang II induced hypertensive mice,but slightly inhibited the increase of vascular thickness,collagen accumulation,ROS production,inflammatory and fibrotic factors expression in mice.AAV-APN treatment significantly inhibited renal ROS production,collagen accumulation,abnormal expression of inflammatory factors and fibrotic factors in mice4.Deletion of FGF21 ablated the protective effect of APS against AngII-induced hypertension,vascular and renal damage: loss of FGF21 ablated the blood pressure lowering effect of APS,and attenuated the protective effect of APS on Ang II-induced vascular injury,following with increased Ang II induced vascular thickness,collagen accumulation,aortic ROS productions and the expression of inflammatory and fibrotic factors in WT mice.FGF21 deficiency ablated the protective effect of APS on Ang II induced renal injury: compared with angiotensin II positive control group,APS significantly reduced vascular thickness,collagen II accumulation,ROS formation and expression of inflammation and fibrosis factors in WT mice;in contrast,the therapeutic effects of APS were ablated in FGF21 KO mice.