Effects of sodium butyrate on plaque formation and inflammatory responses in atherosclerotic rats through the NOD1/RIP2/NF-κB signaling pathway
This study aimed to investigate the effects of sodium butyrate(NaB)on plaque formation and inflammatory responses in atherosclerotic(AS)rats through the nucleotide-binding oligodomain-like receptor 1(NOD1)/receptor-interacting protein 2(RIP2)/NF-κB signaling pathway.AS model on 41 rats was given by combination of balloon injury and high-fat diet(HFD),and a total of thirty-six rats were successfully modeled.Thirty-six AS rats were divided into model group,NaB group,and NaB+NOD1 agonist y-D-glu-mesodiaminopimelic acid(iE-DAP)group,with 12 rats in each group.The sham operation group rats were only given exposure of left common carotid artery and successive suture.The model group,NaB group and NaB+iE-DAP group were cultured with HFD while the sham operation group was cultured routinely.NaB group was gavaged with 10 g/(kg·d)NaB,NaB+iE-DAP group was gavaged with 10 g/(kg d)NaB and peritoneally injected with 1 mL/(each week)iE-DAP;Model group and sham operation group were gavaged and peritoneally injected with the same volume saline;All the above treatments lasted for twelve weeks.Aorta histomorphology was evaluated by H-E staining.The levels of serum TG,TC,LDL-C,HDL-C,ox-LDL,MCP-1,hs-CRP,TNF-α,and IL-1 were measured by ELISA.Immunohistochemistry was performed to measure ICAM-1 protein expression in the aorta and western blotting was used to measure the protein levels of NOD1,RIP2 and NF-κB in the aorta.The results showed that the aorta lesion was severe in the model group,alleviated in the NaB group and aggravated in the NaB+iE-DAP group.Compared to those of the sham operation group,the serum levels of TG,TC,LDL-C,ox-LDL,MCP-1,hs-CRP,TNF-α,and IL-1,the positive rate of aortic ICAM-1,the expression levels of NOD1,RIP2 and nuclear NF-κB in the model group were significantly increased(all with P＜0.05),while the levels of HDL-C and cytoplasmic NF-κB protein were significantly decreased(both P＜0.05).In the NaB group,all these indexes showed changes in the reverse direction.Compared to those of the NaB group,the above indicators in the NaB+iE-DAP group all increased significantly while HDL-C and cytoplasmic expression of NF-κB decreased(all with P＜0.05).This study suggests that NaB inhibit NOD1/RIP2/NF-κB signaling pathway to relieve plaque formation and inflammatory responses in AS rats.
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