吉法酯预防双氯芬酸所致小肠损伤的实验研究

Protection of Wycakon on dclofenac Sodium induced intestinal injury in rats

目的观察吉法酯对双氯芬酸所致大鼠小肠损伤的预防作用,探讨其可能的预防保护机制。方法用小剂量双氯芬酸灌胃制备大鼠NSAID相关小肠损伤模型,24只健康雄性SD大鼠按照随机数字表法等分成3组:空白对照组、实验对照组、吉法酯保护组。空白对照组按10 ml·kg-1·d-1体质量生理盐水灌胃1次;实验对照组按7.8 mg·kg-1·d-1双氯芬酸溶液灌胃1次;吉法酯保护组造模前1天予吉法酯31.25 ml·kg-1·d-1灌胃1次;次日起,同等剂量吉法酯灌胃1 h后再予双氯芬酸7.8 ml·kg-1·d-1灌胃1次。5 d后处死所有大鼠,观察各组大鼠小肠黏膜大体及病理组织学改变,检测小肠上皮AngⅡ、NF-κB表达及血清TNF-α变化。结果小剂量双氯芬酸可致大鼠小肠黏膜广泛糜烂、多发溃疡,甚至出血、穿孔。吉法酯干预后,大鼠肠黏膜损伤明显减轻,多以肠黏膜局部充血、糜烂为主。实验对照组大鼠小肠大体损伤评分(4.38±1.41)及组织学评分(4.00±1.85)均较空白对照组(0.00±0.00;0.00±0.00)显著升高(P均<0.01);吉法酯保护组大体损伤评分(1.13±1.36)及组织学评分(1.75±0.71)均明显低于实验对照组(P均<0.05)。实验对照组血清TNF-α、肠黏膜NF-κB以及AngⅡ表达均明显高于空白对照组(22.20±5.42 vs 6.19±2.76、5.75±0.46 vs 1.38±1.19、4.33±1.51 vs 1.88±0.83,P均<0.05);通过吉法酯干预,血清TNF-α水平(13.03±6.30)较实验对照组显著降低,肠黏膜NF-κB表达(0.25±0.46)以及AngⅡ表达(1.50±1.31)均较实验对照组明显下降(P均<0.05)。结论吉法酯可下调炎症因子AngⅡ、NF-κB的表达,减少炎症因子TNF-α的释放,对双氯芬酸所致大鼠小肠黏膜损伤具有一定保护作用。

Objective To observe the effect of Wycakon on dclofenac Sodium induced intestinal injury in rats, and discuss the possible preventive protection mechanism. Methods Twenty-four healthy male Sprague-Dawley rats were randomly divided into three groups： blank control group, model control group and Wyeakon group. The blank control group were lavaged with distilled water 10 ml^-1·kg^-1·d^-1, while the model control group were lavaged with dclofenac Sodium 7.8 ml^-1·kg^-1·d^-1. The Wyeakon group were lavaged with Wycakon 31.25 mg^-1·kg^-1·d^-1 and dclofenac Sodium 7.8 ml^-1·kg^-1·d^-1 an hour later. The day before modeling, rats in Wyeakon group were given Wycakon with a dose of 31.25 ml · kg-1. After 5 days, all rats were killed. Morphological and pathological changes of intestinal mucosa in each rat were observed, and TNF-α was tested by radioimmunoassay method, NF-κB and Ang Ⅱ expression were tested by immune-histochemistry method. Results A dose of 7.8 ml·kg^-1·d^-1 dclofenae can cause intestinal mueosa widely erosion, ulcer, even perforation in rats. After the intervention of Wyeakon, intestinal mucosal injury in rats were significantly reduced. Morphological score （4.38 ± 1.41 ） and histological score （4.00 ± 1.85） of model control group were increased significantly compared with blank control group （0. 00 ± 0.00 ; 0.00 ± 0.00, all P 〈 0.01 ） ; morphological scores （1.13 ± 1.36） and histological scores （1.75 ±0.71 ） of Wycakon group were decreased significantly compared with model control group （all P 〈 0.05）. Expression of serum TNF-α, NF-κB and Ang II in intestinal mucosa in model control group were significantly higher than those in blank control group （22.20 ± 5.42 vs 6.19 ± 2.76, 5.75 ± 0.46 vs 1.38 ± 1.19, 4.33 ± 1.51 vs 1.88 ±0.83, all P 〈0.05）. After the intervention of Wycakon, serum TNF-α （ 13.03 ±6.30）, NF-κB （0.25 ±0.46） and AngⅡ （ 1.50 ± 1.31 ） levels were significantly reduced than those in model control group （ all P 〈 0.05 ） NF-κB and AngⅡ , decrease tinal mucosa. Conclusion Wycakon has the effect of mucosal protection. It can inhibit the activity of the expression of TNF-α in the plasma, thus to relief the inflammation reaction of the intestinal mucosa.