Effects of rhein towards ILK/Snail signal pathway during epithelial-mesenchymal transition process of renal tubular epithelial cells in diabetic nephropathy rats / 中国医师杂志

ABSTRACT

Objective:To investigate the expression of integrin-linked kinase (ILK)/zinc finger transcription factor (Snail) signaling pathway in renal tubular epithelial-mesenchymal transition (EMT) in diabetic nephropathy (DN) and the effect of rhein.Methods:Healthy male Wistar rats of 8 weeks old were randomly divided into normal group, diabetic nephropathy group, rhein intervention group and valsartan intervention group, with 12 rats in each group. Streptozotocin (STZ) was used to induce the diabetic nephropathy model, then rhein intervention group and valsartan intervention group were given rhein 100 mg/(kg·d) and valsartan 30 mg/(kg·d), respectively. At the end of the 8th and 16th week, six rats of each group were killed, in situ lavage kidney, take out the kidney tissue of rats after fixed in wax block and slices. Renal tubular interstitial damage index and the relative area of interstitial collagen evaluated by hematoxylin-eosin (HE) and Masson staining respectively. The protein expression of E-cadherin, α-smooth muscle actin (α-SMA), ILK, Snail and matrix metalloproteinase-9 (MMP-2) in renal tubular epithelial cells were detected by immunohistochemistry.Results:Comparing to normal group, the renal tubular interstitial damage index and relative area of renal interstitial collagen of diabetic nephropathy rats were both increased. The expression of E-cadherin in renal tubular epithelial cells decreased and the expression of α-SMA significantly increased ( P<0.05). Comparing with diabetic nephropathy group, in rhein and valsartan intervention groups, the expression of E-cadherin in renal tubular epithelial cells increased, while the expression of α-SMA significantly decreased ( P<0.05). There was no significant difference in the above indexes between rhein intervention group and valsartan intervention group ( P>0.05). Compared to normal group, the expressions of ILK, Snail, MMP-2 increased progressively with the disease ( P<0.05). Compared with diabetic nephropathy group, rhein and valsartan intervention groups showed significant decrease in expression of ILK, Snail, MMP-2 ( P<0.05). There was no significant difference in the above indexes between rhein intervention group and valsartan intervention group ( P>0.05). Conclusions:Rhein could inhibit EMT progression by down-regulating the expression of ILK/Snail signaling pathway in renal tubular epithelial cells of DN rats.