Total glucosides of peony regulate toll-like receptor to inhibit inflammatory response in diabetic nephropathy

Abstract

Diabetic nephropathy (DN) is a common chronic disease affecting people’s life. Total glucosides of peony (TGP) regulates TLR4/NF-κB activation. This study aims at investigating the underlying mechanism of TGP in DN treatment. A retrospective analysis of clinical data was conducted to observe periodic acid-silver metheramine (PASM) staining and detect the expression of TLR4 and VEGF in DN. Additionally, rats were injected with Streptozocin (STZ) (30–60 mg) according to the ratio of 45–65 mg/kg to establish DN model. 8 weeks later, rats of experimental group were intraperitoneally injected with TGP. Kidney was collected for HE staining to observe morphological changes. Fibronectin expression was detected by histochemistry and the level of TLR4/NF-κB pathway-related proteins and apoptosis were detected by Western blot. PASM staining revealed focal tubular atrophy and interstitial fibrosis in DN patients. The renal medulla gradually disappeared and infiltration increased in control group, while inflammatory cells decreased in experimental group. The expression of fibronectin, TLR4 and p-p65 was decreased after TGP treatment. TGP treatment significantly decreased fibronectin expression and TGP treatment-induced inhibition of NF-κB signaling enhanced apoptotic activation of HK-2 cells, which was partially reversed by TLR4 and NF-κB inhibitors. TGP can inhibit inflammatory response of DN via regulating TLR4/NF-κB.