摘要Background:Disrupted Ca2+ homeostasis contributes to the development of colonic dysmotility in ulcerative colitis (UC),but the underlying mechanisms are unknown.This study aimed to examine the alteration of colonic smooth muscle (SM) Ca2+ signaling and Ca2+ handling proteins in a rat model of dextran sulfate sodium (DSS)-induced UC.Methods:Male Sprague-Dawley rats were randomly divided into control (n =18) and DSS (n =17) groups.Acute colitis was induced by 5％ DSS in the drinking water for 7 days.Contractility of colonic SM strips (controls,n =8 and DSS,n =7) was measured in an organ bath.Cytosolic resting Ca2+ levels (n =3 in each group) and Ca2+ transients (n =3 in each group) were measured in single colonic SM cells.Ca2+ handling protein expression was determined by Western blotting (n =4 in each group).Differences between control and DSS groups were analyzed by a two-sample independent t-test.Results:Average tension and amplitude of spontaneous contractions of colonic muscle strips were significantly enhanced in DS S-treated rats compared with controls (1.25 ± 0.08 g vs.0.96 ± 0.05 g,P =0.007;and 2.67 ± 0.62 g vs.0.52 ± 0.10 g,P =0.013).Average tensions of carbachol-evoked contractions were much weaker in the DSS group (1.08 ± 0.10 g vs.1.80 ± 0.19 g,P =0.006).Spontaneous Ca2+ transients were observed in more SM cells from DSS-treated rats (15/30 cells) than from controls (5/36 cells).Peak caffeine-induced intracellular Ca2+ release was lower in SM cells of DSS-treated rats than controls (0.413 ± 0.046 vs.0.548 ± 0.041,P =0.033).Finally,several Ca2+ handling proteins in colonic SM were altered by DSS treatment,including sarcoplasmic reticulum calcium-transporting ATPase 2a downregulation and phospholamban and inositol 1,4,5-trisphosphate receptor 1 upregulation.Conclusions:Impaired intracellular Ca2+ signaling of colonic SM,caused by alteration of Ca2+ handing proteins,contribute to colonic dysmotility in DSS-induced UC.