| Objective: Glomerulosclerosis(GS) is the same effects which is caused by many reasons after glomeruli injury. The pathophysiological basis is the unbalanced of two sort factors which affect the Extracelluar matrix (ECM).The disorders of lipid metabolism is one of dangerous factors of GS. The purpose of our investigation is to establish the GS model which induced by adriamycin and high cholesterol diet,use HRI treatment,observe the effects on the blood lipid and the index of GS(GSI),and the changes in the two sort factors which effect ECM.In all, it can further explore lovastatin possible mechanism which ameliorate GS .Methods: The 24 male wistar rats were randomly divided into three groups: normal control group(A),non-treated nephropathy group(B),lovastatin-treated group(C),and there were 8 rats in each group.Group A rats were fed a standard chow, Group B rats were fed high cholesterol diet.Group C rats were fed high cholesterol diet and supplied lovastatin as a dose of 4mg/kg daily. At the fist time, the rats from group B,C were injected with adriamycin(5mg/kg) through tail vein. On the subsequent day, the rats from group C were gastric-perfused with lovastatin every day. The urine and blood of rats were collected to examine 24-hour urinary protein excretion and serum biochemisty value. After they were harvested at week 12, the right kidney of all rats were cut to have pathological analysis and to detect the expression of TGF-β1,PDGF-BB,TIMP-1 in renal tissue with immunohistochemistry method.Results: (1) Before experiment examined norms of every group have no significant difference, at week 2 group B,C show proteinuria, at week 6 they show hypoalbumenia and hypercholesterol and at week 12 the rats except group A show glomerulosclerosis of different extent. (2) From week 2 to the end of experiment, 24-hour urinary protein excretion of group B,C is higher than that of group A. That of group C is lower than that of group B at week 5. (3) At week 6, group B,C display hypoproteinemia and hypercholesterolemia. At week 12, serum albumin and high density lipoprotein(HDL) of group C is significantly higher than that of group B (p<0.01),but the cholesterol(Ch) and triglycerides(TG) and low density lipoprotein(LDL) is lower than that of group B. (4) Most glomeruls of group B show segmental glomerulosclerosis and many renal tubules are involved. The renal injury of group C is lighter than that of group B. Compared with group B, GSI and the number of foam cell of group C is significantly decreased.(5) The expression of TGF-β1 and PDGF-BB and TIMP-1 of group C is weaker than that group B.(6) Serum Ch was positively correlated with GSI and percentage of glomerular with form cell (r =0.86,0.88,respectively, P<0.01).The expression of TGF-β1 and PDGF-BB and TIMP-1 were respectively correlated positively with GSI(r=0.89,0.93,0.96, P<0.01).Conclusion: Lovastatin not only can decrease serum lipid and proteinuria in glomerulosclerosis rats model fed by high cholesterol diet and injected adriamycin,but also can ameliorate glomerulosclerosis by lowering the level of TGF-β1 and PDGF-BB and TIMP-1 in kidney . |
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