Polygala Fallax Hemsl Extract Protects Kidneys In Db/db Diabetic Nephropathy Mice By Inhibiting TLR4/My D88/NF-κb Signaling Pathway

Objective: To observe the pathological changes of urine microalbumin,serum creatinine,blood urea nitrogen and kidney structure of db/db mice by Extract of Polygala fallax Hemsl(PFH).As well as the regulation of the levels of TLR4,My D88,NF-κB,MMP-9,IL-6,TNF-α-related protein factors,to explore the therapeutic effect and potential mechanism of the drug on the inflammation of diabetic nephropathy.Methods: Thirty male db/db mice were divided into 5groups,namely model group,positive group(gliquidone,gliquidone,GLI),PFH high-dose,medium-dose and low-dose groups.And 6 db/m mice were used as blank control,each group was treated by gavage every day for 8 weeks.The general state of db/db mice was observed every day;the urine microalbumin,serum creatinine and blood urea nitrogen and other biochemical indicators of db/db mice were detected.The pathological changes of kidney tissue were observed by H&E staining and PAS glycogen staining.The expressions of TLR4,My D88,NF-κB and MMP-9 in renal tissue were determined by immunohistochemistry,quantitative real-time PCR and Western blotting,and TNF-α,MCP-1,IL-6 were detected by Elisa kit.IL-18 and IL-1β expression of inflammatory factors.In addition,in this experiment,the acute toxicity of mice was observed by giving KM mice the maximum dose of PFH(300 times higher dose group),and the toxicity of PFH to mice was evaluated.Results: PFH significantly improved the body weight of diabetic nephropathy mice,decreased the levels of urinary microalbumin,serum creatinine and blood urea nitrogen in db/db mice,and significantly improved renal pathological lesions.In addition,PFH significantly inhibited the expression of TLR4,My D88,NF-κB,MMP-9 and related inflammatory factors and chemokines TNF-α,MCP-1,IL-6,IL-18 and IL-1β in renal tissue,delaying the development of diabetic nephropathy.In the acute toxicity experiment,the KM mice in the administration group did not die,and there was no significant difference in the biochemical indexes such as the organ index,total protein in serum,serum creatinine,alanine aminotransferase and the blank group compared with the blank group.Conclusion: PFH is a low toxicity,safe and effective drug.PFH may attenuate the inflammatory response in the kidney tissue of db/db diabetic nephropathy mice by inhibiting the TLR4/My D88/NF-κB signaling pathway,and play a protective role in the kidneys of diabetic nephropathy mice.