| BACKGROUD: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease(CD), is a syndrome with abdominal pain, diarrhea, mucus pus and bleed. IBD show a long-term performance of recurrent attacks of inflammatory bowel disease, with a chronic and expendable features. The disease incidence and prevalence rates in the world have reported that there continued to increase. Etiology and pathogenesis of IBD is still unclear. Recent studies have shown that immunomodulatory disorder is one of the reasons leading to the IBD, while the Th17 cell subsets and regulatory T-cell disorder in which an important part. At this stage, IBD treatments is very limited, mainly 5-aminosalicylic acid preparations, corticosteroids, immunosuppressive agents and the recent use of biological agents, mainly, but these drugs there are different limitations and side effects. Therefore, the search for new and effective drugs has been a IBD research. TGP (total glucosides of paeony, TGP) extracted from peony root, mainly paeoniflorin (Paeoniflorin, PF). Studies have shown that TGP has a certain immune regulation, inflammation suppression function, but its role in the treatment of IBD remain unclear.AIM:①To observe IL-6, IL-17, IL-23 and TGF-β1, Foxp3 and other indicators of changes in TNBS-induced experiments colitis in rats, analysis of these indicators and experimental colitis relations.②The TGP on TNBS-induced colitis in rats experimental intervention effects on experimental colitis explore whether the anti-inflammatory effect.③observed TGP on TNBS-induced experimental colitis in rats IL-6, IL-17, IL-23 and TGF-β1, Foxp3 and other test indicators.④Analysis of TGP intervention effect on experimental colitis and the experimental relationship between the indicators to explore the TGP in experimental colitis in the possible pharmacological mechanism. .METHODS: Colitis model was induced in 50 rats by rectal administration of trinitro- benzene sulfonic acid(TNBS)dissolved in ethanol.In these 50 models rats, 10 model rats were treated with 100mg/kg TGP, 10 rats were treated with 50mg/kg TGP and 10 rats were treated with 100mg/kg TGP. respectively, 10 model rats served as model control group, and 10 model rats were treated with 100mg/kg olsalazine as drug controls, Other 10 rats receiving 0.9% NaC1 solution served as normal controls. After 2-week intervention, the colonic macroscopic damage index (CMDI) and tissue damage index (TDI) were evaluated, the serum levels of interleukin-6 (IL-6), IL-17 and IL-23 were determined by ELISA, and the colonic expression of TGF-β1 and Foxp3 was determined by immunehistochemical method.RESULTS:①Compared with the normal control group, the colitis model group CMDI, TDI, DAI mean was lower (0.90±0.74vs6.88±0.84,0.7±0.48vs5.63±0.48,0.11±0.05vs1.41±0.21, all P<0.05) , serum IL-6, IL-17 and IL-23 levels was lower (62.12±16.034vs350.21±79.80,188.04±72.71vs547.38±270.67,11.80±1.82vs 44.13±0.08, all P<0.05), TGF-β1 and Foxp3 of colonic tissue were significantly higher (190.15±51.79vs 69.45±11.15,206.21±76.09vs116.08±21.02, all P<0.05). 5-ASA,middle and high-dose TGP can significantly reduce the DAI mean, CMDI, and TDI (0.96±0.15,1.18±0.21,0.92±0.20 vs1.41±0.21; 2.78±2.11,3.78±1.86,3.56±1.94 vs 6.88±0.84; 2.22±0.83,3.56±1.51, 2.44±1.51 vs 5.63±0.74, all P<0.05), reduce serum IL-6, IL-17 and IL-23 levels (156.53±52.06,210.54±106.58,168.77±63.91 vs 350.21±79.80; 317.41±80.91,317.40±76.67,244.76±126.58 vs 547.38±270.67; 17.17±4.26,18.55±5.76,14.51±1.69 vs 44.13±30.08, all P<0.05), increased colonic tissue TGF-β1 and Foxp3 levels (177.72±37.28,131.46±62.87, 154.59±49.55 vs 69.45±11.15; 244.84±118.45,184.38±84.56, 201.74±86.09 vs 116.08±21.02, all P<0.05).②Colitis model group, the colon tissue TGF-β1, Foxp3 and serum IL-6, IL-17 and IL-23 was negatively correlated (r=-0.936, r=-0.985, r=-0.944 and r=-0.871, r=-0.944, r=-0.852, both P <0.05); TGP high-dose treatment group, colonic tissue TGF-β1, Foxp3 and serum IL-6, IL-17 and IL-23 was negatively correlated (r=-0.839, r=-0.869, r=-0.835 and r=-0.870, r =-0.884, r=-0.911, both P<0.05); 5-ASA treatment group, the colon tissue TGF-β1, Foxp3 and serum IL-6, IL-17 and IL-23 was negatively correlated (r=-0.854, r=-0.724, r=-0.954 and r=-0.931, r=-0.873, r=-0.740, both P<0.05). Colitis model group, the colon tissue TGF-β1, Foxp3 and rat DAI, CMDI, TDI score was negatively correlated (r=-0.928, r=-0.950, r=-0.883 and r=-0.925, r=-0.905, r=-0.774, both P<0.05); TGP high-dose group colon tissue TGF-β1, Foxp3 and rat DAI, CMDI, TDI score was negatively correlated (r=-0.685, r=- 0.728, r=-0.765 and r=-0.765, r=-0.765, r=-0.737, both P<0.05); 5-ASA treatment group, the colon tissue TGF-β1, Foxp3 and rat DAI, CMDI, TDI score was negatively correlated with (r=-0.926, r=-0.894, r=-0.934 and r=-0.811, r=-0.860, r=-0.824, both P<0.05). Model group, serum IL-6, IL-17, IL-23 and rat DAI, CMDI, TDI score was positively correlated (r=0.874, r=0.930, r=0.885; r=0.919, r=0.947, r=0.928 ; r=0.766, r= 0.890, r=0.794, both P<0.05); TGP high-dose treatment group, serum IL-6, IL-17, IL-23 and rat DAI, CMDI, TDI score were positively related (r=0.746, r=0.954, r=0.929; r= 0.730, r=0.911, r=0.894; r=0.811, r=0.762, r=0.719, both P<0.05); 5-ASA treatment group, serum in IL-6, IL-17, IL-23 and rat DAI, CMDI, TDI score was positively correlated (r= 0.873, r=0.944, r=0.873; r=0.787, r=0.929, r=0.896; r=0.843, r=0.756, r=0.860, both P <0.05).③TGP high-dose group and 5-ASA was no significant statistical difference.CONCLUSION: In rat serum, IL-6, IL-17 and IL-23 expression increased in the TNBS-induced colitis. TGF-β1 and Foxp3 reduced the expression in colitis colon tissue. In contrast, IL-6, IL-17 and IL-23 expression decreased in TGP treatment groups and 5ASA treatment group in serum , TGF-β1 and Foxp3 increased expression in colon tissue. TGP may be through up-regulating TGF-β1 and Foxp3 levels, and promote CD4+CD25+Treg cells expressed to reduce IL-6, IL-23 expression, and inhibiting the activation of Th17 cell populations, reducing IL-17 and IL-6 expression, thereby reducing TNBS-induced experimental colitis with colitis symptoms and injury in rats. |
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