The Study Of Anti-inflammatory Effect And Mechanism Of4-aminosalicylic Acid And5-aminosalicylic Acid

Ulcerative colitis (UC), as one of the most serious diseases in gastrointestinal tract exceptcanceration, is a kind of chronic and nonspecific colitis. The main clinical symptoms of UCincluce abdominal pain, diarrhea and rectal tenesmus. Drug therapy has been the main treatmentof UC for a long time. Among the drugs,5-aminosalicylic acid (5-ASA) and its prodrugs areimportant drugs for the treatment of mild to moderate UC. In recent years, many experimentalstudies have confirmed that4-aminosalicylic acid (4-ASA) has the similar effect with5-ASA inthe treatment of UC and has been used to the UC patients, who can not tolerate sulfasalazine(SASP). The anti-inflammatory effects and mechanism of4-ASA and5-ASA have been studiedat both animal and cellular levels in his thesis. There are three chapters in this thesis.In chapter one, the therapy effects of4-ASA and5-ASA were studied in the rats afterinduced by TNBS to build the model of UC. The experimental results showed that the diseaseactivity index (DAI) score, gross score and histological score of rats in model group weresignificantly higher than the rats in control group (p＜0.05). After given SASP,4-ASA and5-ASA, the extent of colitis in rats of each group was significantly mitigate, and the DAI score,gross score and histological score were significantly lower (P<0.05) compared with the modelgroup.In chapter two, the inhibition effects of4-ASA and5-ASA on IL-6、NO、iNOS mRNA andiNOS protein expressions in LPS-induced RAW264.7cells were investigated. The experimentalresults showed that,4-ASA: Compared with the normal group, the IL-6, NO, iNOSmRNA andiNOS protein expression of model group cells were significantly upregulated (P<0.05).Compared with the model group, there were no significant differences in the IL-6, iNOSmRNAand iNOS protein expression of10μg/ml4-ASA treatment group cells (P＞0.05), but NOexpression was significantly lowered (P<0.05). The IL-6, NO, iNOSmRNA and iNOS proteinexpressions of100μg/ml and1000μg/ml4-ASA treatment group cells were significantly lower(P<0.05).5-ASA: Compared with the normal group, the IL-6, NO, iNOSmRNA and iNOSprotein expression of model group cells were significantly upregulated (P<0.05). Compared withthe model group, the IL-6, NO, iNOSmRNA and iNOS protein expression of10,100and1000μg/ml5-ASAtreatment group cellswere significantly lowered (P<0.05).In the last chapter, the inhibition effects of4-ASA and5-ASA on the phosphorylation ofJNK1/2and p38MAPK and IκBα protein expression in LPS-induced RAW264.7cells werestudied. The experimental results showed that,4-ASA: Compared with the normal group, the p-JNK1/2, p-p38and IκBα protein expression of model group cells were significantlyupregulated (P<0.05). Compared with the model group, there were no significant differences inthe p-JNK1/2protein expression of10μg/ml and100μg/ml4-ASA treatment group cells (P＞0.05), but the p-JNK1/2protein expression of1000μg/ml4-ASA treatment group cells wassignificantly lowered (P<0.05). There were no significant differences in the p-p38and IκBαprotein expression between10,100and1000μg/ml4-ASA treatment group cells and modelgroup(P＞0.05).5-ASA: Compared with the normal group, the p-JNK1/2, p-p38and IκBαprotein expression of model group cells were significantly upregulated (P<0.05). Compared withthe model group, there were no significant differences in the p-JNK1/2protein expression of10μg/ml and100μg/ml5-ASA treatment group cells (P＞0.05), but the p-JNK1/2proteinexpression of1000μg/ml5-ASA treatment group cells was significantly lowered (P<0.05). Thep-p38protein expression of10,100and1000μg/ml5-ASA treatment group cells wassignificantly lower than the model group (P<0.05). There were no significant differences in theIκBα protein expression between10,100and1000μg/ml5-ASA treatment group cells and modelgroup (P＞0.05).The results from the above three chapters can be concluded that both4-ASA and5-ASAhave significant anti-inflammatory effects, but the anti-inflammatory mechanism of them isdifferent.4-ASA showed the anti-inflammatory effect by inhibiting the phosphorylation ofJNK1/2while5-ASAinhibiting the phosphorylation of both JNK1/2and p38.