The Effect And Mechanism Of Atrovastatin On TGF-β₁ Of 5/6 Nephrectomy In Rats

Objective To determine the effect and mechanism of atrovastatin on TGF- β1 of progressive glomerulassclerosis in rats. Methods 36 healthy 50-days-old Wistar rats were equally divided into 3 groups by chance, namely, normal control, progressive glomerulassclerosis made by 5/6 nephrectomy and the group reserved atrovastatin (6mg/kg.d) after the operation of 5/6 nephrectomy for 4 weeks or 9 weeks. Water were poured down into the stomach of rats in the group of the progressive glomerulassclerisis and the normal control every day. 4 weeks later six rats in every group would be killed after the final operations. The same to the other 6 rats of each group 9 weeks after the operations. Urinary protein excretion and serum lipid were assayed,and renal glomerulosclerosis index,the expression of transforming growth factor- β1(TGF- β1) were observed in the 5/6 nephrectomized rats by immunohistochemistry. RT-PCR were used to examin the TGF- β 1 mRNA in the kidneys.Results 1)4 weeks after the operation urinary protein excretion and TGF- β1 of atrovastatin-treated progressive glomerularsclerosis rats was substantially deseased (p<0.05)compared with the untreated 5/6 nephrectomized group. Serum total cholesterol, low-density lipoprotein was significantly lower in treatment group than that in progressive glomerulassclerosis rats without treatment (p<0.05). Moreover, the renal damage was also less marked in atrovastatin-treated rats. However, triglycerides were unchanged significantly. Immunohistochemical examination and RT-PCR revealed that the expression of TGF- β1 were also sharply lower in treatment group than that in glomerulassclerosis group. 2) 9 weeks after the operation, urinary protein excretion (p<0.05), serum cholesterol (P<0.05) and low-density lipoprotein (P<0.05) of atrovastatin-treated prigressive glomerularslerosis. group were decreased compared with the untreated 5/6 niphrectomized group Pathohistological study revealed that there were less glomerular matrix in atrovastatin-treated group than that in glomerularslerosis group. The expression of TGF- β1(P<0.05) was remarkly reduced in the guoup of treatment. Conclusion Our reserch indicate that atrovastatin can reduce proteinuria, serum cholesterin, low-density lipoprotein and lesion glomerular injury in 5/6 nephrectomized rats. It can decrease the expression of TGF- β1 in renal tissue and protect the kidney.