Effect of Banxia Xiexintang on NLRP3/Caspase-1 Pyroptosis Pathway in Rats with Ulcerative Colitis / 中国实验方剂学杂志

ABSTRACT

ObjectiveTo explore the effect of Banxia Xiexintang （BXT） on the NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific protease-1 （Caspase-1） pyroptosis pathway and its downstream factors in rats with ulcerative colitis （UC）， and to explain the mechanism of BXT in the treatment of UC. MethodSD rats were randomly divided into normal control group， model group， low- and high-dose BXT groups （6.3， 12.6 g·kg-1·d-1）， and salazosulfapyridine （SASP） group （0.42 g·kg-1·d-1）， with 7 rats in each group. The UC model was induced by intragastric administration of 2.5% dextran sodium sulfate （DSS） solution for 10 days， followed by drug intervention for 7 days. The general state of rats was observed during the experiment， and the disease activity index （DAI） score was calculated during the administration period. At the end of the experiment， colonic tissues were collected for hematoxylin-eosin （HE） staining to observe the pathological changes and the curative effect of BXT. Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA transcriptional levels of NLRP3， Caspase-1， gasdermin D （GSDMD）， and interleukin （IL）-1β in colonic tissues. Western blot was used to detect the protein expression of NLRP3， Caspase-1， GSDMD， and IL-1β in colonic tissues to explore the therapeutic mechanism of BXT. ResultCompared with the normal control group， the model group showed increased DAI score， pathological changes in colonic tissues， and up-regulated mRNA and protein expression of NLRP3， Caspase-1， GSDMD， and IL-1β （P<0.05， P<0.01）. Compared with the model group， the groups with drug intervention showed reduced DAI scores and improved pathological changes in colonic tissues. The mRNA and protein expression levels of NLRP3， Caspase-1， GSDMD， and IL-1β in colonic tissues of the BXT groups were significantly down-regulated or tended to be down-regulated， especially in the low-dose BXT group （P<0.05， P<0.01）. ConclusionBXT can inhibit pyroptosis and alleviate inflammation in rats with UC by regulating the NLRP3/Caspase-1 pathway.