Exploring the mechanism by which acupuncture and moxibustion reduce colonic mucosal inflammation in rats with ulcerative colitis (UC) based on the P2X7R-NLRP3 inflammasome pathway

Objective To explore the mechanism of acupuncture and moxibustion for ulcerative colitis (UC) from the perspective of the P2X7 receptor (P2X7R)-nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome pathway. Methods Sprague-Dawley rats were randomly assigned to a normal (N) group, a model (M) group, a herb-partitioned moxibustion (HM) group, and an electroacupuncture (EA) group. For modeling, the rats drank 4% dextran sulfate sodium for 7 d. Rats in the HM group and EA group received 7 consecutive days of herb-partitioned moxibustion or EA at bilateral Tianshu (ST25), respectively. The histopathological change in colon tissue was observed by hematoxylin-eosin (HE) staining; immunofluorescence staining was used to detect the protein expression of related molecules in the colon tissue, and enzyme-linked immunosorbent assay was used to detect the concentrations or contents of related molecules in the serum and colon tissue. Wild-type (WT) and P2X7R gene knockout (KO) mice were used to construct UC models, histopathological changes in the colon tissue were observed by HE staining, and the NLRP3 protein expression in the colon tissue was observed by immunohistochemistry. Results Compared with the N group, the colon histopathological score in the M group was significantly increased, and the protein expression of P2X7R, NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), Caspase-1, interleukin-1β (IL-1β), and interleukin-18 (IL-18) in the colon tissue and the protein levels of IL-1β and IL-18 in the serum were significantly increased ( P <0.05). Compared with the M group, the histopathological scores of the colon in the HM group and the EA group were significantly decreased, and the protein expression levels of P2X7R, NLRP3, ASC, Caspase-1, IL-1β, and IL-18 in the colon tissue and the protein level of IL-18 in the serum were significantly decreased ( P <0.05). After UC modeling, the colonic mucosal epithelial damage and inflammatory cell infiltration in P2X7R KO mice were less than those in WT mice, and the NLRP3 protein expression in the colon was also decreased compared with that in WT mice ( P <0.05). Conclusion HM and EA at Tianshu (ST25) may inhibit the protein activities of P2X7R, NLRP3, ASC, and Caspase-1 in the colon tissue of rats with UC, thereby reducing the downstream molecules IL-1β and IL-18 in the P2X7R-NLRP3 inflammasome pathway to relieve UC inflammation.