Effects of 5-aminosalicylic acid on proliferation and apoptosis of colonic epithelial cells in patients with ulcerative colitis

Abstract

Objective To investigate proliferation and apoptosis of colonic epithelial cells from ulcerative colitis (UC) patients with active new-onset, remission and active recurrent stages, and to study the effects of 5-aminosalicylic acid (5-ASA) on proliferation and apoptosis of colonic epithelial cells during the treatment of inducing remission and maintanence remission. Methods From January 2002 to December 2012, twelve patients with mild-to-moderate UC who received treatment and long-term follow-up and achieved remission with 5-ASA and received long-term maintanence treatment with it were assigned to UC group. At the same period, 10 healthy individuals with negative endoscopy results or solitary colonic polyp were assigned to control group. The biopsy tissues from colonoscopy for pathological examination of patients in UC group at new-onset active stage, remission stage and recurrence stage were obtained. Levels of proliferation marker Ki-67 and apoptosis of colonic epithelial cells were determined by immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, respectively.Data were expressed by median(lower quartile, upper quartile). Kruskal-Wallis test and Mann-Whitney test were performed to compare the differences between groups and Bonferroni method was used for correction. Results The median proliferation indexes (PI) of colonic epithelial cells of UC patients at new-onset active period, remission period and recurrent active period were 31.65%(19.14%, 39.66%), 12.30%(11.11%, 14.10%) and 44.15%(33.65%, 52.45%), respectively, which were all higher than those of control group (7.89%(6.54%, 8.86%))there were statistically significant differentes among four groups (H=30.033, P<0.01); those of new onset active period and recurrent active period were both higher than remission period, and the differences were statistically significant (all P<0.05/6). The median apoptosis indexes (AI) of colonic epithelial cells in UC patients at new-onset active period, remission period and recurrent active period were 24.18%(17.81%, 27.16%), 44.19%(43.41%, 50.55%), 41.24%(33.78%, 46.24%), respectively, which were all higher than those of control group (2.65%(2.48%, 2.98%)), there were statistically significant differences among four groups (H=31.563, P<0.01); and those of remission and recurrent active period were both higher than new-onset active period (all P<0.05/6). The median apoptosis/proliferation ratios of control group, new onset active period, remission period and recurrent active period were 0.320 0(0.275 5, 0.425 0), 0.749 9(0.634 9, 1.115 8), 3.282 8(3.133 1, 4.406 8) and 1.008 2(0.801 9, 1.099 2), respectively, there were statically significant differences among four groups (H=29.441, P<0.01); those of new onset active period and recurrent active period were both lower than that of remission period and the differnces were statistically significant (both P<0.05/6). Conclusions Proliferation and apoptosis imbalance in colonic epithelial cells of UC patients is one of the important mechanisms for the pathgensis of UC. 5-ASA does not promote the proliferation of epithelial cells during UC remission period. Key words: Colitis, ulcerative; 5-aminosalicylic acid; Proliferation; Apoptosis