The Study On The Role And Mechanism Of Sinomenine And Sulfasalazine In Experimental Colitis Of Mice Model

Objective To investigate the role and mechanism of sinomenine andsulfasalazine(SASP) in experimental colitis of mice model.Methods Seventy healthy SPF grade male Kunming mice were randomly and evenlydivided into seven groups: normal group, model group, low dose sinomenine group, highdose sinomenine group, low dose sinomenine plus SASP group, high dose sinomenineplus SASP group and SASP group. The mouse stool characters, changes in body weightand fecal occult blood were record and disease activity index (DAI) was scored. The nextday after7days of the intervention, all mice were sacrificed and specimens of the colonwere obtained and lesion injury was scored. The specimens of inflammatory part and ulcersite of colon were taken for histological examination and injury scoring. The expression ofMKK (mitogen-activated protein kinase kinase)5, ERK(extracellular signal-regulatedkinase)5, MKK(mitogen-activated protein kinase kinase)7, JNK (Jun N-terminal kinase),NF-κB (nuclear factor κB) at mRNA level in colon tissue were detected by reversetranscription-polymerase chain reaction (RT-PCR). t-test was performed for comparisonbetween groups.Results Compared with normal group, the DAI score, general colon score andhistological injury score significantly increased in model group(0.57±0.52vs3.40±0.66，1.10±0.99vs3.00±1.05，2.70±2.06vs11.40±1.71) and the difference wasstatistically significant(all P<0.01). Of low dose sinomenine group, high dose sinomeninegroup, low dose sinomenine plus SASP group, high dose sinomenine plus SASP group and SASP group, the score of injury was5.50±1.43,4.00±1.49,6.80±1.75,4.80±1.32and5.40±1.58respectively, all were lower than that of model group(11.40±1.71) and thedifference were statistical significant（tscore of injury=8.35、10.31、5.94、9.66and8.15，allP<0.05）.The score of lesion injury of high dose sinomenine group, high dose sinomenineplus SASP group and SASP group was1.40±1.26、1.70±1.06and1.80±1.32respectively, which were lower than that of model group(3.00±1.05) and the differencewere statistical significant(t=3.07、2.75and2.25，all P<0.05). Compared with model group,the expression of MKK5(51.94±9.16,6.53±0.85,72.03±17.44,16.80±7.15,24.29±3.40vs1061.00±627.45), ERK5(50.71±11.09,17.87±2.74,119.91±47.26,21.09±3.92,34.74±3.05vs1117.97±428.64), MKK7(57.98±17.22,13.52±2.56,74.09±21.24,15.81±1.35,21.34±3.74vs727.21±136.67), JNK(55.99±9.65,10.41±2.62,71.83±16.91,14.11±3.10,18.71±4.12vs694.21±283.57) and NF-κB(67.41±10.21,13.79±1.43,86.57±18.61,16.62±3.15,21.68±2.96vs731.07±174.03) at mRNA level in colonsignificantly decreased in sinomenine low dose group, sinomenine high dose group,sinomenine low dose plus SASP group, sinomenine high dose plus SASP group and SASPgroup, and the difference was statistically significant(all P<0.01). The effects ofsinomenine high dose group were better than those of corresponding sinomenine low dosegroup and sinomenine singlely group were better than corresponding combination drugtherapy group. The effects of SASP group were better than those of sinomenine low dosegroup but worse than those of either sinomenine high dose plus SASP group orsinomenine high dose group.Conclusion Sinomenine could efficiently improve the inflammatory reaction in the mousemodel of oxazolone induced colitis and the mechanism might be related with ERK5, JNKand NF-κB signaling pathways. The higher dose, the efficacy was more significant.Antagonism may exist between sinomenine and SASP.