Total Glucosides of Paeony Attenuate Renal Tubulointerstitial Injury in STZ-Induced Diabetic Rats: Role of Toll-Like Receptor 2

Abstract

Accumulating evidence suggested that macrophages induce tubulointerstitial injury. Total glucosides of paeony (TGP), extracted from Paeonia lactiflora, has presented anti-inflammatory activities in diabetic kidney disease. This research will investigate the protective effect of TGP on renal tubulointerstitium and its mechanism in streptozotocin-induced diabetic rats. TGP was administered orally at a dose of 50, 100, and 200 mg·kg⁻¹·d⁻¹ for 8 weeks. Tubulointerstitial injury was quantified, followed by immunohistochemistry analysis of renal α-smooth muscle actin (α-SMA), E-cadherin (E-cad) expression, nuclear factor kappa B (NF-κB)-p-p-65⁺, Toll-like receptor (TLR)2⁺, and ED-1⁺ cell infiltration in renal tubulointerstitium. Renal TLR2⁺ macrophages were detected by double immunohistochemical staining. Western blotting was used to detect the TLR2 expression. Histologically, there was marked accumulation of TLR2⁺, NF-κB-p-p-65⁺, ED-1⁺ cells, and ED-1⁺TLR2⁺ cells (macrophages) in the diabetic kidney and TGP treatment could alleviate it. Accompanying with that, the tubulointerstitial injury was ameliorated, α-SMA expression was lower, and E-cad expression was higher compared with the diabetic rats. Western blot analysis showed that the expression of TLR2 protein was significantly increased in the kidney of the diabetic rats, whereas TGP treatment reduced it. Our study showed that TGP could prevent renal tubulointerstitium injury in diabetic rats through a mechanism that may be at least partly correlated with suppression of increased macrophage infiltration and the expression of TLR2.