| Objective: To discuss the function of TIMP—1, TGF--β,and PKC--β in renal impairment of the diabetic rats and study the possible mechanism that Losartan and Simvastatin protect the renal in the diabetic rats.Methods:The 58healthy,8—week old Wister rats were randomly divided into 5 groups:normal control group(C group) diabetic control (D group);diabetis rats treated with losartan (D1 group);diabetc rats treated with Simvastatin (D2 group);diabetic rats treated with both losartan and simvastatin (D3 group);There nine or ten rats in every group. All rats of diabetic groups were injected with streptozotocin(STZ) according to 60mg/kg at abdominal cavity while the rats of normal control were injected with saline.If the FBG excceded 16.5mmol/L and continued 3 days, the rats were confirmed to be patterns successively. During the experiment all rats randomly drink and eat,all rats of diabetic groups were not treated with insulin or other anti—diabetes drugs. The rats of D1andD2 group were perfused with losartan (20mg/kg/d) and Simvastatin(2mg/kg/d) respectively and the rats of D3 group were perfused losartan and simvastatin. At the end of the 8th week of study, the urine and blood samples were collected and 12—hour UAER were measured by immunoradiometry method FBG, plasma cholesterol, plasma trigly ceride and creatinine were determined respectirely. Take out of the kidneys. desiccate, weighing, stabilize, paraffin embed. The expression of TIMP-1 TGF-β, PKC-β in all rats' renal tissue were measured by immunohistochemistry method.Results: 1. the 12—hour UAER of D1,D2,D3 group were significantly decreased and kidney weigh exponent were ameliorate significantly. (P0.01). The blood lipid level of every group had no significant difference.2 .After 8 weeks, the expression of TIMP-1 ,TGF-β, PKC-β in diabetes rats were significantly increased than these in normal control group. 3. Both losartan and simvastatin can significantly inhibit the expression of TIMP-1 ,TGF-β, PKC-β, but can't make it recovery. Treatment with both losartan and Simvastatin can make the expression decreased further.4. Compare the paraments of D1 and D2 group, there was no significant difference.Conclusion: 1. At the end of the 8th week, the blood sugar of the wister rats induced by STZ increased obviously and was loss of weight, the kidney weigh exponent and 12—hour UAER increased The expression of TIMP-1 ,TGF-β, and PKC-β in the renal tissue increased, which indicted that TIMP-1 ,TGF-β, PKC-β had participated in the impairment of the kidney.2. Losartan can protect the kidney from diabetic injury and its mechanism probably is that losartan inhibit the progress of angiotensin-Ⅱ binding to its recepter and affect DAG-PKC'S activation. In the end, the expression of PKC-β decreased, which reduced the expression of TGF-β, TIMP-1. 3. Simvastatin can protect the kidney from diabetic injury by inhibiting the expression of TIMP-1, TGF-β, PKC-β, which independent of lowering the level of blood lipid. Simvasfatin can weaken the acfivation of RAS in kidney by inhibiting the activation of PKC-β, then the expression of TIMP-1 ,TGF-β reduced.4. Combined treatment of losartan and simvastatin had significant superiority. This superiority suggest that the two drugs protect the kidney by different links but act on the same eytokine. If drug treament could cooperate blood sugar contrd the effect of treatment would be better.
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