Objective:

2

To observe the effects of Chinese medicine (CM)

Polygonum cuspidatum

(PC) on adenosine 5'-monophosphate-activated protein kinase (AMPK)

forkhead box O3α (FOXO3α)

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:

2

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

Western blot

enzyme linked immunosorbent assay

and immunohistochemistry were used to detect AMPK

FOXO3α

TLR4

NLRP3

and MCP-1 mRNA and protein levels in renal tissue or serum.

Results:

2

Compared with the normal group

the mRNA transcription levels of AMPK and FOXO3α in the model group were significantly down-regulated

and protein levels of AMPKα1

pAMPKα1 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 AMPKα1

pAMPKα1 and FOXO3α in the high-dose PC group

AMPKα1 and pAMPKα1 in the mediumdose PC group

and pAMPKα1 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 AMPKα1

pAMPKα1 and FOXO3α 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:

2

PC up-regulated the expression of AMPK and its downstream molecule FOXO3α 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.