田七对水浸应激大鼠胃黏膜损伤及超氧化物歧化酶活性和丙二醛与一氧化氮含量的影响(英文)

Effect of Panax notoginseng on gastric mucosal injury, superoxide dismutase activity, malondialdehyde and nitric oxide contents in rats with water immersion restraint stress

背景:田七是治疗胃黏膜溃疡的有效药物。许多临床报道证实田七对胃黏膜溃疡具有保护作用。目的:分析田七对水浸应激大鼠胃黏膜损伤的保护作用机制。设计:随机对照动物实验。单位:哈尔滨医科大学大庆校区基础部。方法:实验于2004-09/2005-10在哈尔滨医科大学病理生理学实验室完成。①实验分组:Wistar大鼠48只,体质量180～200g,随机分成6组,即正常对照组,应激模型组,甲氰咪呱药物对照组,田七低剂量组(4mg/次),田七中剂量组(8mg/次),田七高剂量组(12mg/次),每组8只。②实验方法:甲氰咪呱药物对照组:将甲氰咪呱片剂研磨成粉末,与蒸馏水混合成混悬液(1片:10mL),每次向大鼠胃内灌注5mL,3次/d;田七剂量组:将田七胶囊内的药末与蒸馏水混合成混悬液,按浓度配置成0.8,1.6,2.4g/L,每个浓度的药物给药方法同甲氰咪呱。运用水浸应激的方法制作大鼠应激模型。③实验评估:实验观察胃黏膜大体及病理组织学改变,并测定组织中超氧化物歧化酶活性、丙二醛及一氧化氮的含量。主要观察指标:①胃黏膜大体及病理组织学改变。②各组胃黏膜组织匀浆中丙二醛、一氧化氮含量和超氧化物歧化酶活性的变化。结果:48只大鼠全部进入结果分析。甲氰咪呱药物对照组与应激模型组大鼠相比,胃黏膜出血与糜烂明显减轻,超氧化物歧化酶活性明显下降(12.61±0.87),(1.03±0.60)mkat/g,而一氧化氮水平稍高(5.76±1.35),(0.97±0.58)nmol/g;应激模型组丙二醛含量明显高于正常对照组,两者具有显著差异[(3.10±1.13),(0.09±0.02)μmol/g,P<0.01]。田七低、中、高剂量组大鼠的实验结果除了一氧化氮水平降低与甲氰咪呱处理组不同外,其他无明显差异。结论:田七对水浸应激大鼠胃黏膜损伤具有明显的保护作用,该保护作用与剂量无关。保护机制可能与田七清除氧自由基产物有关,其作用机制与甲氰咪呱不完全相同。

BACKGROUND： Panax notoginseng is an effective medicine for curing gastric mucosal ulcer. There are many clinical reports that Panax notoginseng protects gastric mucosa. OBJECTIVE： To investigate the protective mechanism of Panax notoginseng on the gastric mucosal injury induced by water immersion restraint stress in rats. DESIGN： A randomized controlled animal trial.SETTING： School of Basic Medical Sciences, Daqing Branch of Harbin Medical University. MATERIALS： The study was conducted in the laboratory of Department of Pathophysiology of Harbin Medical University from September 2004 to October 2005. Forty-eight Wistar rats were used, either male or female, weighing 180-230 g. METHODS： The 48 Wistar rats were randomly divided into six groups with 8 rats in each group： normal control group, stress model group, cimetidine treatment group, Panax notoginseng of low, middle and high-dose groups （4, 8, 12 mg/time）. In the cimetidine treatment group, cimetidine tablets were grinded into powders, then mixed with distilled water to prepare into suspension （1 tablet：10 mL）, which was perfused intragastrically （5 mL）, 3 times a day; In the Panax notoginseng groups, the powders in Panax notoginseng capsules were mixed with distilled water to prepare into suspension of corresponding concentrations （0.8, 1.6, 2.4 g/L）, then administrated the same as those in the cimetidine treatment group. Stress models in rats were established by means of water immersion restraint stress. The gross and pathohistological changes of gastric mucosa were observed, and the activity of superoxide oxidase （SOD） and contents of malondialdehyde （MDA） and nitric oxide （NO） were determined. MAIN OUTCOME MEASURES：①Gross and pathohistological changes of gastric mucosa;②Changes of MDA and NO contents and SOD activity in the homogenate of gastric mucosa. RESULTS： All the 48 rats were involved in the analysis of results. The gastric mucosal hemorrhage and erosion in the cimetidine treatment group were reduced obviously as compared with those in the stress model group, SOD activity was obviously decreased [（12.61±0.87）, （1.03±0.60） mkat/g], whereas the NO content was a little higher [（5.76±1.35）, （0.97±0.58） nmol/g]. The MDA content was obviously higher in the stress model group than in the normal control group [（3.10±1.13）, （0.09±0.02） μmol/g, P〈0.01]. There were no obvious differences between the Panax notoginseng groups and the cimetidine treatment group except that the NO contents were decreased in the in Panax notoginseng groups. CONCLUSION： Gastric mucosal injury induced by water immersion restraint stress can be significantly protected by Panax notoginseng, which is not dose-dependent. The protective mechanism may be associated with that Panax notoginseng can eliminate the product of oxygen-derived free radicals, and it is not totally the same as that of cimetidine