Jichu yixue yu linchuang (Sep 2021)
Thalidomide alleviates renal fibrosis of nephrotic syndrome mice
Abstract
Objective To investigate the effects of thalidomide on epidermal growth factor receptor (EGFR)/extracellular signal regulated kinase (ERK) signaling pathway and renal fibrosis of nephrotic syndrome mice. Methods The mice were randomly divided into control group and model group with 15 in each to prepare membranous nephropathy model, thalidomide group was given thalidomide solution 100 mg/kg, leflunomide group was given leflunomide solution 5 mg/kg per day for four weeks. The 24-hour urine protein (24 h-Upro) was measured before, after and 4 weeks after treatment; after 4 weeks of treatment, the biochemical indexes of mice in each group were detected by automatic biochemical analyzer; the levels of serum interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α) were detected by ELISA.HE staining, Masson staining and periodic acid Schiff (PAS) staining were used to observe the renal pathological changes in each group; the expression of EGFR,ERK mRNAs and proteins were detected by RT-qPCR and Western blot. Results Compared with the control group, the 24 h-Upro in the model group was significantly increased (P＜0.05). After 4 weeks of treatment,the glomerulus volume of the model group was larger, there were vacuolar lesions in the renal tubules, and the epithelial cells of the renal tubules had the deposition of eosinophilic protein, and the 24h-Upro, the contents of TC, TG, BUN and Scr in serum, the expression of IL-6, IL-8 and TNF-α in serum, the mRNA level of EGFR and ERK in renal tissue and the protein expression of p-EGFR/EGFR and p-ERK/ERK were all significantly higher(P＜0.05). As compared with those in the model group, the above pathological symptoms in leflunomide group and thalidomide group were significantly reduced, and the 24 h-Upro, the contents of TC, TG, BUN and Scr in serum, the expressions of IL-6, IL-8 and TNF-α in serum, the mRNA level of EGFR and ERK in renal tissue, the protein expressions of p-EGFR/EGFR and p-ERK/ERK were all significantly lower (P＜0.05). Conclusions Thalidomide may alleviate renal damage and inhibit renal fibrosis by inhibiting EGFR/ERK signaling pathway.
