川芎嗪对溃疡性结肠炎肠粘膜过氧化物酶体增殖物激活受体γ及核因子κB的影响

Effect of Tetramethylpyrazine on the Expression of Peroxisome Proliferators-activated Receptor γ and Nuclear Factor-κB with Ulcerative Colitis

目的:通过观测经川芎嗪治疗前后过氧化物酶体增殖物激活受体γ(PPARγ)、核因子κB(NF-κB)和肿瘤坏死因子(TNF)-α的变化,探讨川芎嗪治疗溃疡性结肠炎(UC)的作用机制。方法:以噁唑酮诱导小鼠UC模型,并随机分为实验对照组(CN)、模型组(OXZ)、川芎嗪治疗组(TMP)和0.9%氯化钠治疗对照组(NS)。观察UC炎症评价指标(DAI,大体、组织学损伤评分,MPO值);采用荧光定量PCR法检测各组肠粘膜PPARγ、NF-κBp65、TNF-αmRNA的表达量;免疫组化法检测PPARγ、NF-κBp65蛋白的表达。结果:与CN组比较,OXZ组的炎症评价指标均明显增高(P<0.01),PPARγ表达量明显下降(P<0.01)、NF-κBp65及TNF-α表达量均显著升高(P<0.01)。应用川芎嗪后,UC的炎症评价指标均较NS组明显降低(P<0.01),PPARγ表达量明显升高(P<0.01)、NF-κBp6及TNF-α表达量均下降(P<0.01)。结论:川芎嗪对UC的结肠粘膜有保护作用,其机制可能与PPARγ的激活,NF-κB的抑制,TNF-α等炎症因子表达的减低有关。

Objective：To investigate the role of PPAR γ、NF-κB and tμmor necrosis factor-α in the ulcerative colitis（UC）treatment by TMP.Methods：Mouse UC model was induced by oxazolone,and randomized to four groups：50% ethanol infused normal control group（NC）,UC group（OXZ）,TMP treat group（TMP） and NS treat group（NS）.Disease active index（DAI）,macroscopic and histological damage was observed and evaluated.Colonic MPO was measured by chemical method.The mRNA level of PPARγ,NF-κB p65 and TNF-α in colonic mucosa was quantitated by real-time PCR.The expression of PPARγ and NF-κB p65 were also detected by immunohistochemistry in protein level.Results：Oxazolone colitis was constructed successfully with marked inflammation in colonic mucosa examined macroscopically and histologically.Compared with those of the NC group,the expression of PPARγ was decreased in OXZ group but NF-κB p65,TNF-α were higher（P〈0.01）.Both symptoms and the lesions of colonic mucosa were slighter in the animals treated with TMP than those of NS group（P〈0.01）.And the expression of PPARγ was higher in TMP group than NS group（P〈0.01）,but NF-κB p65 and TNF-α were decreased（P〈0.01）.Conclusion：TMP has protective effect against mouse ulcerative colitis,and its mechanism may be related with the activation of PPARγ,inhibition of NF-κB activation,and reduction of TNF-α.