云母对大鼠非甾体抗炎药相关小肠损伤的保护及对肿瘤坏死因子-α、核因子-κB的影响

Effect of Muscovite on Non-steroidal Anti-inflammatory Drug Associated Intestinal Injury and Its Influences on Tumor Necrosis Factor-αand Nuclear Factor-κB in Rats

目的观察云母对大鼠非甾体抗炎药(non-steroidal anti-inflammatorydrugs,NSAIDs)相关小肠损伤的保护作用及其对炎症因子肿瘤坏死因子-α(TNF-α)、核因子-κB(NF-κB)表达的影响,探讨其肠黏膜保护的可能机制方法用小剂量双氯芬酸灌胃制备大鼠NSAIDs相关小肠损伤模型,按随机数字表法将24只雄性SD大鼠随机分成3组:空白组、模型组、云母干预组,每组8只空白组以1 mL/(100 g·d)生理盐水灌胃,模型组以7.8 mg/(kg·d)双氯芬酸灌胃,云母组于造模前1d给予云母120 mg/(kg·d)灌胃,造模当天起,云母干预组每天120 mg/(kg·d)灌胃1 h后,再以7.8 mg/(kg·d)双氯芬酸灌胃,连续5d后处死所有大鼠。观察大鼠小肠黏膜大体及组织学损伤并作评分,放免法测定血清TNF-α变化,免疫组化法检测肠上皮NF-κB表达。结果小剂量双氯芬酸可致大鼠肠黏膜损伤,出现腹水,腹膜粘连,小肠黏膜红斑糜烂、多发溃疡、肠腔狭窄,并可见穿孔等;云母干预组大鼠肠黏膜损伤明显减轻,腹腔炎症明显改善,多以小肠黏膜局部充血水肿、糜烂为主。模型组大鼠小肠损伤大体评分(4.38±1.41)及组织学评分(4.00±1.85)均较空白组(0.00±0.00;0.00±0.00)显著升高(均P<0.01);云母组小肠损伤大体评分(1.25±1.58)及组织学评分(1.75±0.71)均较模型组明显降低(P<0.05)模型组血清TNF-α水平及肠黏膜NF-κB表达明显高于空白组(22.20±5.42vs 6.19±2.76、5.75±0.46vs 1.38±1.19,P<0.01,P<0.05);云母干预组大鼠的血清TNF-α水平(9.61±4.02)及肠黏膜NF-κB表达(0.13±0.35)较模型组显著下降(P<0.01)。结论云母可有效减轻大鼠NSAID相关小肠损伤,可抑制小肠黏膜NF-κB活性,下调炎症因子TNF-α表达,对NSAIDs所致小肠损伤具有防治作用。

Objective To examine the efficacy of muscovite on non-steroidal anti-inflammatory drug （NSAID） associated intestinal injury in rats,and its influences on the expressions of inflammatory factors,tumor necrosis factor-α（TNF-α） and nuclear factor-κB（NF-κB）,for researching its possible mechanism of intestinal mucosal protection.Methods NSAID associated intestinal injury in rat was induced by intra-gastric infusion of diclofenac. Twenty-four male Sprague-Dawley rats were randomly and equally assigned to three groups：normal control group,model control group and Muscovite group,8 in each group.The normal control group received physiological saline 1 mL/100g and the other two groups received diclofenac 7.8 mg/kg respectively every day for 5 days;while to the Muscovite group,Muscovite 120 mg/kg was gastric infused once on the day before modeling, followed with 120 mg/kg per day,given an hour before diclofenac infusion in the modeling days.All rats were killed on the 6th day,their gross changes and histological injury of intestinal mucosa were observed and scored,serum level of TNF-αwas assayed in radioimmunoassay and NF-κB activity was determined by immuno-histochemistry. Results The small dosage diclofenac administration can cause intestinal damage,revealing obviously erythema,erosion,multiple ulcer,intestinal stricture,even perforation,etc.Intestinal injury in the Muscovite group was obviously milder than that in the model control group,only showed changes of local congestion,e- dema and erosion.The scores of gross and histological intestinal features in the model control group were 4.38±1.41 and 4.00±1.85,while in the Muscovite group were 1.25±1.58 and 1.75±0.71,respectively,all higher than those in the normal control group（0.00±0.00 and 0.00±0.00,P0.01 and P0.05）,respectively, but the elevation in the model control group were more significant（P0.05）.Similar results were shown in comparisons of TNF-αand NF-κB levels between groups,the values were 6.19±2.76 and 1.38±1.19 in normal control;22.20±5.42 and 5.75±0.46 in model control;9.61±4.02 and 0.13±0.35 in the Muscovite group, respectively（all P0.01）.Conclusion Muscovite could effectively reduce the NSAID associated intestinal mucosal injury by inhibiting the activity of NF-κB in intestinal mucosa,and down-regulating the expression of TNF-αin blood plasma,so muscovite is proved to have protective function for intestine.