Objective: 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 a...Objective: 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: 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 m L·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 m RNA and protein levels in renal tissue or serum. Results: Compared with the normal group, the m RNA 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 6 th and 8 th weeks(P<0.01 or P<0.05). The m RNA 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 6 th week, the mRNA transcription levels of AMPK in the high-and medium-dose groups, and protein expression levels of AMPKα1, p AMPKα1 and FOXO3α in the high-dose PC group, AMPKα1 and p AMPKα1 in the mediumdose PC group, and p AMPKα1 in the low-dose PC group were significantly up-regulated(P<0.01 or P<0.05); the m RNA transcription and prot展开更多
基金Supported by the National Natural Science Foundation of China(No.81473516 and No.30973918)
文摘Objective: 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: 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 m L·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 m RNA and protein levels in renal tissue or serum. Results: Compared with the normal group, the m RNA 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 6 th and 8 th weeks(P<0.01 or P<0.05). The m RNA 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 6 th week, the mRNA transcription levels of AMPK in the high-and medium-dose groups, and protein expression levels of AMPKα1, p AMPKα1 and FOXO3α in the high-dose PC group, AMPKα1 and p AMPKα1 in the mediumdose PC group, and p AMPKα1 in the low-dose PC group were significantly up-regulated(P<0.01 or P<0.05); the m RNA transcription and prot
