姜黄素对大鼠肠黏膜肿瘤坏死因子α及白细胞介素4的调控作用

Effect of curcumin in modulating the tumor necrosis factor alpha and interleukin 4 in intestinal mucosa of rats

目的:探索中药姜黄素制剂对肠炎模型大鼠肠黏膜肿瘤坏死因子α及白细胞介素4的调控作用。方法:实验于2002-01/2005-01在南方医科大学动物实验中心及南方医院消化研究所完成。180只大鼠随机分为正常乙醇对照、模型、柳氮磺胺吡啶对照、姜黄素预防、姜黄素治疗、N-乙酰半胱氨酸对照组,每组30只。除正常乙醇对照组用体积分数为0.5的乙醇2mL灌肠外,其余各组均采用50g/L三硝基苯磺酸50mg溶于体积分数为0.5的乙醇2mL中灌肠,建立大鼠肠炎模型。柳氮磺胺吡啶对照组在造模前3d给予5g/L柳氮磺胺吡啶;姜黄素预防组在造模前3d给予20g/L姜黄素;姜黄素治疗组在造模后立即给予20g/L姜黄素;N-乙酰半胱氨酸对照组在造模前3d给予2g/LN-乙酰半胱氨酸。造模2周后处死存活大鼠,分析大鼠体质量。应用半定量反转录聚合酶链反应检测肿瘤坏死因子α(致炎因子)及白细胞介素4(抑炎因子)mRNA的表达。结果:①实验大鼠造模过程中死亡30只,进入结果分析150只,正常乙醇对照组30只、模型组18只、柳氮磺胺吡啶对照组23只、姜黄素预防组28只、姜黄素治疗组24只、N-乙酰半胱氨酸对照组27只。②大鼠体质量分析:柳氮磺胺吡啶组、姜黄素预防组、姜黄素治疗组、N-乙酰半胱氨酸组显著高于模型组(P<0.05),N-乙酰半胱氨酸组显著高于柳氮磺胺吡啶组、姜黄素预防组、姜黄素治疗组(P<0.05),柳氮磺胺吡啶组、姜黄素预防组、姜黄素治疗组组间比较无显著差异(P>0.05)。③姜黄素可显著抑制肠黏膜肿瘤坏死因子αmRNA的高表达,各组均未见白细胞介素4mRNA的表达。结论:姜黄素与柳氮磺胺吡啶治疗对改善大鼠消瘦效果相同。姜黄素能使肠炎大鼠肠黏膜肿瘤坏死因子α水平下调,从而对其肠黏膜有免疫保护作用,经提纯的天然单体姜黄素可能具有肠黏膜炎性病变的组织修复作用。

AIM:To ascertain the effect of curcumin in modulating tumor necrosis factor alpha(TNF-α)and interleukin(IL-4) in intestinal mucosa of rats with inflammatory bowel disease(IBD). METHODS:This experiment was performed in Experiment Center for Animals,Southern Medical University and Institute of Gastroenterology,Nanfang Hospital from January 2002 to January 2005.Totally 180 rats were randomly divided into ethanol control group,model group,sulfasalazine control group,curcumin prevention group,curcumin treatment group and N-acetylcysteine(NAC) control group with 30 rats in each group.Gastric perfusion of 50 mg trinitrobenzene sulfonic acid(50 g/L) dissolved in 2 mL ethanol(500 mL/L) was performed in all the groups except only 2 mL ethanol(500 mL/L) in the ethanol control group to establish the IBD model of rats.Sulfasalazine 5 g/L,curcumin 20 g/L and NAC 2 g/L were given to the sulfasalazine control group,curcumin prevention group and NAC control group respectively 3 days before modeling,and curcumin 20 g/L was given to the curcumin treatment group immediately after modeling.Two weeks after modeling,the surviving rats were sacrificed to analyze their body mass.mRNA expression of TNF-α(proinflammatory cytokine) and IL-4(anti-inflammatory cytokine) in intestinal mucosa was assessed by semiquantitative reverse-transcription polymerase chain reaction. RESULTS:①Thirty rats died during the experiment,so totally 150 rats were involved in the result analysis,including 30 in ethanol control group,18 in model group,23 in sulfasalazine control group,28 in curcumin prevention group,24 in curcumin treatment group and 27 in NAC control group.②The body mass of rats was all significantly more in the sulfasalazine control group,curcumin prevention group,curcumin treatment group and NAC control group than in the model group(P< 0.05),and also significantly more than in the NAC group than in the sulfasalazine control group,curcumin prevention group and curcumin treatment group(P< 0.05),but insignificantly different among the sulfasalazine control group,curcumin prevention group and curcumin treatment group(P >0.05).③Curcumin could obviously suppress the high expression of TNF-αmRNA in intestinal mucosa.However,the expression of IL-4 mRNA had not been found in each group. CONCLUSION:Curcumin and sulfasalazine has the same effects in improving emaciation in rats.Curcumin can downregulate the level of TNF-αin intestinal mucosa of rats with IBD,and thus prevent the intestinal mucosal immunity.The purified natural monomer curcumin maybe has the function of repairing the intestinal mucosa with inflammatory lesion.