Renal Protection Of Macrophage Depletion In Angiotensin Ⅱ Hypertensive Mice

ObjectiveMacrophage infiltration is tightly contacting with hypertensive renal injury,the present study investigated renal protection of macrophage depletion by clodronate liposome(CL)in angiotensin(Ang)Ⅱ-induced hypertension mice.MethodsTwenty-four C57BL/6 mice were randomly divided into four groups: normal control,normal plus CL treatment(CL,0.1 ml/10 g BW,2 times/week by tail vein injection),Ang Ⅱ infusion(1.4 mg/kg/day,implanted by mini-pump),Ang Ⅱ plus CL treatment for 14 days.The systolic blood pressure(SBP)was measured by tail-cuff method,SBP was measured at 3 time points: at baseline,7days and 2 weeks.Expression of macrophages in renal tissue was determined by Immunofluorescence.Expression of the protein in the renal tissue was determined by Western blot analysis.ResultsCompared with control mice,Ang Ⅱ infusion significantly increased systolic blood pressure(SBP),proteinuria,renal structural damage,renal macrophage infiltration associated with higher expression of proinflamamtory cytokine tumor necrosis factor(TNF)α and inteleukin(IL)1β.CL markedly reduced renal macrophage infiltration,renal structural and functional impairment,and the expression of the proinflammatory cytokines with a mild reduction in SBP in Ang Ⅱ mice.Furthermore,Ang Ⅱ also induce renal fibrosis with increased expression of fibrotic factors TGF-β1 and fibronectin as well as the expression of NADPH oxidae subunits gp91 phox and p22 phox,depletion of macrophage by CL effectively reversed renal fibrosis and the changes in those molecules induced by Ang Ⅱ.ConclusionsOur results show that macrophage is main contributor to Ang Ⅱ hypertensive renal injury,the underlying mechanisms may involve increased production/release of macrophage-derived inflammatory cytokine and oxidative stress,which cause renal structural and functional injury.