Study on the mechanism of interleukin-6 in the colonic motility changes of depression rat model

Abstract

[Abstract] Objective To study the changes of colonic motility in chronic stress-induced depression rat model, the association between interleukin 6 （IL-6） and depression and its effects on contraction of colonic smooth muscle in vitro. Methods There were 30 healthy adult Wistar rats, of which chronic stress-induced depression model was created in 15 rats and the other 15 rats were in control group. The ratio of sugar consumption to body weight and the percentage of sugar preference were tested in these two rats groups through sugar preference experiments. The behavioral changes of two rats groups were detected by open field test. Colonic motility was evaluated with simulated fecal discharge experiment, and the serum IL-6 level was measured with enzyme linked immunosorbent assay （ELISA）. IL-6 in colon tissue at mRNA level was determined by RT-PCR. The contraction ability of rat colonic smooth muscle was observed. The colonic smooth muscle of control group was treated with different concentration of IL-6, the effects of IL6 on normal colonic smooth muscle and its response to acetylcholine （Ach） were evaluated. Results In model group, the ratio of sugar consumption to body weight was 0. 12±0. 03, the percentage of sugar preference was 16. 17%-±2.61%, total walking distance was （741.54±341.10） cm and total times of upright was 15.69＋ 8.00, which were all significantly lower than those of control group （0.18±0.02, 25.54±2.32%, 1336.20 cm±698.80 cm and 24.87±7.90, respectively） （P= 0. 041, 0. 044, 0. 002 and 0. 001）. It took （109. 78±48.00） min for defecating in model group, which was significantly longer than that of control group （28.00±11.10） min （P=0. 002）. The IL6 levels were high both in the serum and colon tissue of model group rats. The response of colonic smooth muscle to Aeh was weaker in model group than that of control group （P=0. 035）. In model group, there were no significant difference in the response of colonic smooth muscle to IL-6 at 200, 500 and 1000 pg/ml （P =0. 935,0. 825, 0. 766）. After Ach added, there was significant difference in the response to Aeh between IL-6 at 500, 1000 pg/ml （R=1.14804-0. 1000 and 1. 1361±0. 1500） and control group only added with Ach （R= 1. 6100±0. 4500） （P= 0. 000 and 0. 004）. Conclusion IL-6 level increase in chronic stress-induced depression rat model and causes smooth muscle contraction disorder through reducing the sensitivity of intestinal smooth muscle to Ach. Key words: Stress; Depressive disorder; Disease models, animal; Colon; Kinetics; Interleukin-6