Protective effects of low-dose rapamycin combined with valsartan on podocytes of diabetic rats

摘要

The aim of this study was to study the impacts and the mechanisms of low-dose rapamycin combined with valsartan on the renal functions of diabetic nephropathy (DN) rats. 50 SD rats were randomly divided into the normal control group (group A, n=10) and the DN model group (n=40), the DN model group was intraperitoneally injected streptozocin (STZ) for the modeling, which were then equally divided into the DN group (group B), the rapamycin group (group C, orally administrated rapamycin 1 mg/kg/d), the valsartan group (group D, orally administrated valsartan 30 mg/kg/d) and the combined therapy group (group E, orally administrated rapamycin 1 mg/kg/d + valsartan 30 mg/kg/d). Group A and group B were orally administrated the same amount of 0.5% carboxymethylcellulose. After 8-week treatment, the rats of each group were killed for the renal functional and pathological detection, as well as the expression detection of nephrin and podocin of kidney tissues. Compared with group A, the renal functions of the DN model groups were all decreased, and the pathological changes were significant. Meanwhile, the expressions of nephrin/podocin were reduced (P<0.05); among which group B exhibited the most serious changes, while the situations of group E were improved after the combined treatment, the expressions of nephrin/podocin were increased. Low-dose rapamycin and valsartan could enhance the expressions of nephrin and podocin, reduce kidney damages, thus achieving the protective effects towards the kidneys, and the effects of the combined therapy were superior to those of monotherapy.