Impact of andrographolide on intestinal inflammation in rats with diarrhea type irritable bowel syndrome by regulating the NLRP3/caspase-1 signaling pathway / 中华内分泌外科杂志

ABSTRACT

Objective:To investigate the impact of andrographolide (AND) on intestinal inflammation in rats with diarrhea type irritable bowel syndrome (IBS-D) and its regulatory mechanism on the NLRP3/caspase-1 signaling pathway.Methods:After the IBS-D rat model was established by low concentration acetic acid combined with restraint stress, the rats were grouped into control group, model group, positive drug group, AND low-dose (AND-L) group, AND medium dose (AND-M) group, and AND high-dose (AND-H) group, with 10 rats in each group. The score of fecal traits and fecal water content of rats in each group were detected; the abdominal withdrawal reflex (AWR) of rats in each group was scored; HE staining was applied to observe the changes of colonic histopathology of rats in each group; enzyme linked immunosorbent assay (ELISA) was applied to detect the levels of tumor necrosis factor-α (TNF- α), interleukin-6 (IL-6), interleukin-1 β (IL-1 β), and interleukin-18 (IL-18) in the colon tissue of rats in each group; Western blot was applied to detect the expression levels of NLRP3, ASC, and caspase-1 proteins in the colon tissue of rats in each group. Results:The scores of fecal traits of rats in the control group was 2.43±0.19, fecal water content was 31.76±2.81, AWR score was 0.43±0.02, TNF-α was 123.49±12.35, IL-6 was 76.45±6.23, IL-1 β was 195.76±15.14 and IL-18 was 167.31±13.92, the protein expression levels of NLRP3 was 0.96±0.06, ASC was 1.01±0.08, and caspase-1 was 0.94±0.06. The scores of fecal traits in model group was 6.12±0.58, fecal water content was 65.24±4.13, AWR score was 2.42±0.18, which were higher than those in control group ( P<0.05), the TNF- α in model group was 315.73±19.47, IL-6 was 231.97±14.65, IL-1 β was 435.83±28.67, IL-18 was 382.56±26.84, the protein expression levels of NLRP3 was 2.41±0.18, ASC was 2.23±0.15, and caspase-1 was 2.15±0.16, which were higher than those in control group ( P<0.05). The scores of fecal traits in the low, medium, and high dose AND groups were 5.38±0.46, 4.57±0.38, 3.31±0.27, fecal water content were 54.68±3.67, 46.87±3.75, 38.11±3.10, AWR scores were 1.79±0.16, 1.35±0.10, 0.69±0.04, which were higher than those in model group ( P<0.05), the TNF- α in the low, medium, and high dose AND groups were 268.65±17.23, 224.91±16.36, 178.16±14.65, IL-6 were 187.74±14.57, 159.64±11.39, 124.18±8.62, IL-1 β were 369.51±21.96, 314.72±23.64, 263.93±16.82, IL-18 were 334.72±25.17, 280.16±21.43, 235.67±19.32, the protein expression levels of NLRP3 were 1.94±0.15, 1.56±0.12, 1.25±0.09, ASC were 1.89±0.14, 1.61±0.13, 1.28±0.10, and caspase-1 were 1.76±0.14, 1.49±0.11, 1.20±0.09, which were higher than those in model group ( P<0.05) . Conclusion:AND may alleviate intestinal inflammation in IBS-D rats by inhibiting the NLRP3/caspase-1 signaling pathway.