| Objective: To investigate the effects of Curcumin on thelevels of tumor necrosis factor (TNF)-α, myeloperoxidase (MPO),andthe expression of p-p38MAPK and p38MAPK mRNA in colonic mucosaof mice with dextran sulfate sodium(DSS)-induced UC, and explore theregulating mechanism of p38MAPK signal pathway in pathogenesis ofUC and the effects of curcumin on this pathway．Methods:60healthyfemale BALB/c mice, aged6-7wk, weighed16-20g,were divided into6groups by random numbers table: normal group (A), model group (B),dexamethasone group(C group:1.5mg/kg.d), the curcumin low dosegroup (D group: curcumin15mg/kg.d) the curcumin intermediate dosegroup (E: curcumin30mg/kg.d), curcumin high dose group (Fgroup:curcumin60mg/kg.d),10in each group.Normal group was freely drunkwith water, while the rest of the experimental mice were freely drunkwith5%DSS solution for7days. In treatment group,at the first dayabove doses of curcumins were administered by intraperitonealinjection,in the normal group an equal volume saline was given, while inmodel group an equal volume of2.5%ethanol solution were given.Eating, drinking, hair color, behavoir and stool consistency of mice wereregularily observed in each group during the experiment. Fecal occult blood, and the disease activity index score (DAI) were detected.At8thday,mouse colon tissue was acquired for paraffin-embedded sections and HEstaining; histopathological damage and histological scores were observed;another two tissues were preserved in liquid nitrogen spare. Withenzyme-linked immunosorbent assay (ELISA) tumor necrosis factor(TNF)-α, myeloperoxidase (MPO) levels in colon tissue were measured.With immunohistochemical staining and reverse transcriptasetransaminase polymerase chain reaction (RT-PCR),p-p38MAPKexpression and p38MAPK mRNA expression in colon tissues weredetected. Results:1.in group B,mice symptoms, and histologicalexamination were in line with the UC diagnostic criteria, DAI andhistological assessment were significantly higher than that in groupA.after the therapy of dexamethasone and curcumin, in group C, group D,group E and group F DAI and the histological scores were reducedremarkably.2.The results of ELISA: in group B TNF-α, and MPO levels(382.26±21.82,339.31±13.61) were significantly higher than that ingroup C (257.42±19.04,238.95±11.17) in colon mucosa, in group D(333.67±17.72,298.93±9.94), E group (287.89±19.57,258.60±13.07) andF group (271.10±13.25,248.52±9.24), the differences were statisticallysignificant (all P <0.01),among group C and group D, E group differencewere statistically significant(P <0.05).Compared with group C, TNF-αand MPO levels in F group were no statistically different(P>0.05); there was a signif icant difference between E and Dgroup (P<0.05)and nostatistical difference between E group and F group(P>0.05).3.the resultsof immunohistochemical method: p-p38expression in colonic mucosa(6.80±0.77) of mice in B group was significantly higher than that ingroup A (0.52±0.32), the difference was statistically significant (P<0.01).After drug intervention there were significantly reduced in groupC(2.50±0.82), D group (4.36±1.02), E group (3.62±0.79), F group(3.12±0.63) compared with group B (6.80±0.77,all P<0.01).In C groupthe levels were significantly decreased compared with that in group D,E group (P <0.05).In D group the levels were higher than those in groupE and F group (P <0.05), there was no significant difference betweengroup E and group F (P>0.05).4.The results of RT-PCR: in the B groupsp38MAPK mRNA of colon tissue was significantly higher than that ingroup A, in group C, group D, group E and group F, it was the lowestexpression in Group F. Conclusion: Curcumin may effectively alleviatethe symptoms of DSS-induced acute UC, possibly through p38MAPKsignaling pathways that reduce TNF alpha release of proinflammatoryfactors such as ease of neutrophils infiltration, so as to reduce theintestinal mucosa inflammatory injury in mice and play a therapeutic roleof UC. |
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