胡椒碱对肠易激综合征模型大鼠脑-肠5-羟色胺和突触小泡蛋白的影响

Effect of piperine on 5-HT and synaptophysin expression of rats with irritable bowel syndrome

探讨胡椒碱对慢急性联合应激大鼠的抑郁样行为学和内脏敏感性的改善作用以及对脑肠中5-羟色胺(5-HT)和突触小泡蛋白表达的影响。42只SD大鼠随机分为正常对照组、模型组、胡椒碱(12.5、25、50及100mg·kg 1)组和阳性对照组(丙咪嗪10 mg·kg 1)。采用慢急性联合应激建立肠易激综合征(IBS)模型来评估动物抑郁样行为和肠道敏感性的变化,用高效液相色谱法(HPLC)测定药物对大鼠海马和结肠5-HT含量的影响,用Western blotting法测定大鼠海马和结肠突触小泡蛋白的含量。与正常对照组相比,IBS模型组大鼠强迫游泳不动时间明显增加,糖水消耗量明显降低,大鼠内脏敏感性增加(P<0.05,P<0.01);大鼠海马中5-HT的水平下降,5-羟吲哚乙酸(5-HIAA)与5-HT的比例(5-HIAA/5-HT)增加(P<0.01),而结肠中5-HT的水平升高,5-HIAA与5-HT的比例(5-HIAA/5-HT)降低(P<0.05);大鼠海马中突触小泡蛋白的表达水平下降,结肠中表达水平反而增加(P<0.05)。胡椒碱能逆转上述引起的变化。IBS大鼠存在抑郁状态和内脏敏感性改变,脑肠内5-HT和突触小泡蛋白表达异常,胡椒碱可改善IBS大鼠模型行为学变化,并调节5-HT和突触小泡蛋白的表达。

This study is to explore the amelioration of piperine on chronic acute combining stress rat with depression-like behavior, visceral sensitivity, and its effect on the expression of serotonin （5-HT） and synaptophysin. Forty two SD rats were divided into seven groups： blank group, model group, piperine （12.5, 25, 50 and 100 mg.kg-g） and imipramine （10 mg.kg-l, ip） groups. The rat model of irritable bowel syndrome was established by chronic acute combining stress, and then to evaluate depression-like behavior and visceral sensitivity. The expressions of 5-HT and synaptophysin in the hippocampus and colon were determined by high performance liquid chromatography （HPLC） and Western blotting, respectively. The duration of immobility of IBS rat in the forced swimming test had been significantly increased, the sucrose consumption of IBS rat had been reduced and visceral sensitivity was obviously elevated in the IBS model group as compared with those in the normal control group （P〈0.05, P〈0.01）. As compared with those in the normal control group, the expression of 5-HT significantly decreased, 5-HIAA/5-HT ratio significantly increased in the hippocampus of IBS model group （P〈0.05）, but opposite presentations were noted in the colon （P〈0.05）. As compared with that in the normal control group, the synaptophysin expression in the hippocampus decreased significantlybut obviously increased in the colon （P〈0.05）. Piperine improved the behavior of IBS rats, and reversed the levels of 5-HT and 5-HIAA, and 5-HIAA/5-HT proportion in the hippocampus and colon （P〈0.05）; besides, they significantly reverse the synaptophysin level in the hippocampus and colon （P〈0.05）. The presence of depression and visceral sensitivity had been changed in IBS rats, with abnormal expression of 5-HT and synaptophysin in the brain-gut system. Piperine can ameliorate the changes of the behavior and regulation of serotonin and synaptophysin expression in IBS rat model.