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Objective:To observe the effects of Chinese medicine (CM) Polygonum cuspidatum (PC) on adenosine 5'-monophosphate-activated protein kinase (AMPK),forkhead box O3 α (FOXO3 α),Toll-like receptor-4 (TLR4),NACHT,LRR and PYD domains-containing protein 3 (NLRP3),and monocyte chemoattractant protein-1 (MCP-1) expression in a rat model of uric acid-induced renal damage and to determine the molecular mechanism.Methods:A rat model of uric acid-induced renal damage was established,and rats were randomly divided into a model group,a positive drug group,and high-,medium-,and low-dose PC groups (n=12 per group).A normal group (n=6) was used as the control.Rats in the normal and model groups were administered distilled water (10 mL·kg-1) by intragastric infusion.Rats in the positive drug group and the high-,medium-,and low-dose PC groups were administered allopurinol (23.33 mg·kg-1),and 7.46,3.73,or 1.87 g·kg-1·d-1 PC by intragastric infusion,respectively for 6 to 8 weeks.After the intervention,reverse transcription polymerase chain reaction,Westem blot,enzyme linked immunosorbent assay,and immunohistochemistry were used to detect AMPK,FOXO3 α,TLR4,NLRP3,and MCP-1 mRNA and protein levels in renal tissue or serum.Results:Compared with the normal group,the mRNA transcription levels of AMPK and FOXO3 α in the model group were significantly down-regulated,and protein levels of AMPKα 1,pAMPKα 1 and FOXO3α were significantly down-regulated at the 6th and 8th weeks (P＜0.01 or P＜0.05).The mRNA transcription and protein levels of TLR4,NLRP3 and MCP-1 were significantly up-regulated (P＜0.01 or P＜0.05).Compared with the model group,at the 6th week,the mRNA transcription levels of AMPK in the high-and medium-dose groups,and protein expression levels of AMPKα 1,pAMPKα 1 and FOXO3α in the high-dose PC group,AMPKα 1 and pAMPKα 1 in the medium-dose PC group,and pAMPKα 1 in the low-dose PC group were significantly up-regulated (P＜0.01 or P＜0.05);the mRNA transcription and protein levels of TLR4 and NLRP3 in the 3 CM groups,and protein expression levels of MCP-1 in the medium-and low-dose PC groups were down-regulated (P＜0.01 or P＜0.05).At the 8th week,the mRNA transcription levels of AMPK in the high-dose PC group and FOXO3α in the medium-dose PC group,and protein levels of AMPKα 1,pAMPKα 1 and FOXO3 α in the 3 CM groups were significantly up-regulated (P＜0.01 or P＜0.05);the mRNA transcription levels of TLR4 in the medium-and low-dose PC groups,NLRP3 in the high-and low-dose PC groups and MCP-1 in the medium-and low-dose PC groups,and protein expression levels of TLR4,NLRP3 and MCP-1 in the 3 CM groups were down-regulated (P＜0.01 or P＜0.05).Conclusion:PC up-regulated the expression of AMPK and its downstream molecule FOXO3 α and inhibited the biological activity of TLR4,NLRP3,and MCP-1,key signal molecules in the immunoinflammatory network pathway,which may be the molecular mechanism of PC to improve hyperuricemia-mediated immunoinflammatory metabolic renal damage.

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篇名
来源期刊	中国结合医学杂志（英文版）	学科
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年，卷（期）	2019,（3）	所属期刊栏目
研究方向		页码范围	182-189
页数	8页	分类号
字数		语种	英文
DOI	10.1007/s11655-017-2979-6