Objective:To observe the protective effect of chymotrypsin inhibitors on diabetic hamster kidney and to explore its protection mechanism. Methods:Hamster diabetes mode was established by intraperitoneal injection of streptozotocin(STZ)and all experiment hamsters were divided into five groups. Immunohistochemistry was used to detect chymotrypsin antibody

angiotensin converting enzyme inhibitors(ACE)

NADPH oxidase-4(NOX-4)

NADPH oxidase subunit p22 phox in each group. Immunofluorescence was used to detect the animal protein inhibitor of angiotensin system Mi(renin-angiotensin system

RAS)component

oxidative stress. Realtime PCR and Western blot were used to detect the effect of protein inhibitor of matrix proteins Mi on synthesis of human angiotensinⅡ(ANG-Ⅱ). Results:Immunohistochemistry showed that tubular and glomerular chymotrypsin in diabetic hamsters were significantly increased. Real-time PCR showed that chymotrypsin m RNA levels were generally higher in diabetic hamsters group than in control group(P<0.01)

which returned to normal levels after insulin therapy. Chymotrypsin inhibitors inhibited the increase of angiotensin Ⅱ(ANG-Ⅱ)in kidney of diabetes hamsters

while significantly reduced the level of 8-hydroxy-2’-deoxyguanosine secretion. NOX-4 and p22 phox staining indicated that oxidation products increased significantly in diabetic glomerular and tubular regional groups

and chymotrypsin inhibitors inhibited the increase of oxidation products(P<0.01). Western blot confirmed that the levels of NOX-4 and p22 phox protein were higher in glomerular diabetic group than in control group;chymotrypsin inhibitor significantly reduced its expression. Glomerular transforming growth factor-β(TGF-β1)expression was higher in diabetic group than in control groups;chymotrypsin inhibitor therapy significantly reduced the levels of TGF-β1. Conclusion:Chymotrypsin inhibitors protect diabetic hamster kidney function

the mechanism of which is through reducing renal ANG-Ⅱ levels and oxidative stress levels to protect diabetic kidney damage.