D N Luo1, F J Li, Y Y Zou. 1. Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, China.
Abstract
Objective: To determine the therapic effects of rutaecarpine in dextran sodium sulfate (DSS)induced experimental colitis and explore whether the protective role of rutaecarpine is related to the synthesis and release of CGRP. Methods: Fifty female BABL/c strain mice were randomly divided into untreated model control group and DSS-exposed groups.DSS-exposed groups were given administration of 5% DSS for 7 days and respectively treated with vehicle, rutacarpine(30 mg/kg, 100 mg/kg) , prednisone by intragastric administration from day 8 to day 14.The disease activity index (DAI) scores, the histological scores, the mRNA and protein concentrations of CGRP in colonic tissues were measured. Results: On day 7, the DAI scores of the DSS-exposed groups[vehicle group (8.9±0.9), low-dose Rut group(8.9±0.6), high-dose Rut group(8.2±0.8), prednisone group(8.7±1.6)] were much higher, compared with the untreated model control group(0±0)(P<0.01). The DAI scores on day 14 of the vehicle, rutaecarpine or prednisone treated groups were respectively markedly lower than on day 7(3.2±0.6, 0.9±0.6, 3.1±0.7 vs 8.9±0.6, 8.2±0.8, 8.7±1.6, P<0.05). The DAI score of mice treated with high-dose rutaecarpine was significantly lower, compared with those treated with low-dose rutaecarpine and prednisone.Compared to the untreated model control group, the histological scores in other four groups significantly increased.Comparisons of values among the post-treatment groups had statistical significance (0.2±0.4 vs 6.9±0.9, 4.5±0.9, 2.8±0.8, 5.7±0.7, P<0.01), while the high-dose rutaecarpine group presented the lowest score.The colonic mucosal CGRP mRNA and CGRP protein expressions in groups receiving vehicle, low-dose rutaecarpine and prednisone were significantly reduced than those in the untreated model control group(0.32±0.03 vs 0.15±0.02, 0.18±0.01, 0.22±0.01, P<0.01). The CGRP mRNA and CGRP protein expressions in the untreated model control group was similar to those in the DSS+ high-dose rutaecarpine group with no statistic significance between them(0.32±0.03 vs 0.31±0.02, P>0.05). Pearson correlation analysis between CGRP mRNA levels, CGRP immunohistochemisty levels and DAI, histological scores showed a statistically negative relationship respectively(r=-0.797, -0.819, -0.863, -0.845, all P<0.01). Conclusions: Rutaecarpine can ameliorate the DAI scores and histological scores of ulcerative colitis in mice.Rutaecarpine can upregulate the expressions of CGRP mRNA and CGRP protein.Correlation between CGRP mRNA, CGRP protein levels and DAI scores, histological scores respectively showed a statistically negative relationship.
Objective: To determine the therapic effects of rutaecarpine in dextran sodium sulfate (DSS)induced experimental colitis and explore whether the protective role of rutaecarpine is related to the synthesis and release of CGRP. Methods: Fifty female BABL/c strain mice were randomly divided into untreated model control group and DSS-exposed groups.DSS-exposed groups were given administration of 5% DSS for 7 days and respectively treated with vehicle, rutacarpine(30 mg/kg, 100 mg/kg) , prednisone by intragastric administration from day 8 to day 14.The disease activity index (DAI) scores, the histological scores, the mRNA and protein concentrations of CGRP in colonic tissues were measured. Results: On day 7, the DAI scores of the DSS-exposed groups[vehicle group (8.9±0.9), low-dose Rut group(8.9±0.6), high-dose Rut group(8.2±0.8), prednisone group(8.7±1.6)] were much higher, compared with the untreated model control group(0±0)(P<0.01). The DAI scores on day 14 of the vehicle, rutaecarpine or prednisone treated groups were respectively markedly lower than on day 7(3.2±0.6, 0.9±0.6, 3.1±0.7 vs 8.9±0.6, 8.2±0.8, 8.7±1.6, P<0.05). The DAI score of mice treated with high-dose rutaecarpine was significantly lower, compared with those treated with low-dose rutaecarpine and prednisone.Compared to the untreated model control group, the histological scores in other four groups significantly increased.Comparisons of values among the post-treatment groups had statistical significance (0.2±0.4 vs 6.9±0.9, 4.5±0.9, 2.8±0.8, 5.7±0.7, P<0.01), while the high-dose rutaecarpine group presented the lowest score.The colonic mucosalCGRP mRNA and CGRP protein expressions in groups receiving vehicle, low-dose rutaecarpine and prednisone were significantly reduced than those in the untreated model control group(0.32±0.03 vs 0.15±0.02, 0.18±0.01, 0.22±0.01, P<0.01). The CGRP mRNA and CGRP protein expressions in the untreated model control group was similar to those in the DSS+ high-dose rutaecarpine group with no statistic significance between them(0.32±0.03 vs 0.31±0.02, P>0.05). Pearson correlation analysis between CGRP mRNA levels, CGRP immunohistochemisty levels and DAI, histological scores showed a statistically negative relationship respectively(r=-0.797, -0.819, -0.863, -0.845, all P<0.01). Conclusions: Rutaecarpine can ameliorate the DAI scores and histological scores of ulcerative colitis in mice.Rutaecarpine can upregulate the expressions of CGRP mRNA and CGRP protein.Correlation between CGRP mRNA, CGRP protein levels and DAI scores, histological scores respectively showed a statistically negative relationship.