JBRHA Special Issue n. 2, 2021, MS J141 (AHEAD OF PRINT)



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Secoisolariciresinol diglucoside affects inflammation and response in diabetic nephropathy mice by regulating HSP-70

LB. Yu1, C. Guan2, YH. Dong3, FQ. Meng4, WW. Song5 and BJ. Ji6

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The aim of this study was to investigate the effect and possibility of flax lignans/solarindiglucoside (SDG) in diabetic nephropathy (DN) rats and renal tubular epithelial cells under high glucose stimulation mechanism. Experimental mice were randomly divided into control group (db/m group), diabetic nephropathy model group (db/db group) and SDG treatment group (db/db+SDG group). They were given saline or SDG (1 mg· kg-1·d-1) intraperitoneal injection for 8 weeks. At the end of the experiment, the blood glucose, 24-h urine albumin and blood creatinine levels of rats in each group were detected. TCMK-1 cells were cultured in vitro and in serum-free DMEM medium for 24 h. They were divided into control group (control), high glucose group (HG), HG+SDG group, HG+VER (VER.HSP70 specific inhibition Agent) group, HG+VER+pc-DNA-3.1 (negative control) group and HG+VER+pcDNA-3.1-TLR4 overexpression group. Real-time PCR detected TNF-α, IL- in kidney tissue and cells, IL-1β mRNA expression, Western blot analysis of TLR4 and HSP70 protein expression. Compared with the db/m group, the fasting blood glucose, 24-h urine albumin and serum creatinine levels of the db/db group were significantly increased (P<0.05). SDG can significantly reverse the above indicators in db/db mice Increased (P<0.05). The relative expression of inflammation-related factors TNF-α, IL-6, and IL-1β mRNA in db/db rats increased significantly (P<0.05). At the molecular level, we found that SDG can inhibit HSP70 protein table and reduce TLR4-mediated inflammation. SDG can slow down the TLR4-mediated inflammation in the kidney of diabetic rats by regulating the level of HSP-70 to achieve kidney protection.

Keywords:

HSP-70, SDG, inflammation, diabetic nephropathy, TLR4

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