The Experiment Study Of Renal Protective Function Of Chymase Inhibitor In Diabetes Hamsters Model

ObjectiveObserve Chymase inhibitior protect against renal function indiabetes and offers a new therapeutic target for diabetic nephropathy.MethodsDiabetes model of hamsters was prepared by STZ injection.4groups were divided as diabetes group, insulin group, ramipril groupand chymase inhibition group. The ROS component: NOX-4, p22phox;RAS component: ACE, rennin, ANG-I, ANG-II, TGF-β were checkedfor the protective effect in kidney.ResultsRenal chymase expression was markedly upregulated in diabetichamsters. Oral administration of chymase inhibitor completelyameliorated proteinuria, the overexpression of transforming growthfactor-β and fibronectin in glomeruli, and renal mesangial expansion,by normalizing the increase in intrarenal angiotensin II levels indiabetic hamsters independently of blood pressure levels. In contrast,ramipril did not show such sufficient effects. These effects occurred inparallel with improvements in superoxide production and expression ofNAD(P)H oxidase4and p22p hoxin glomeruli.ConclusionsThis study showed that chymase inhibitior may protect againstelevated intrarenal angiotensin II levels, oxidative stress, and renaldysfunction in diabetes.