中药肠吉安对肠易激综合征内脏高敏感模型大鼠的作用及其机制

Effect of Changji'an on Visceral Hypersensitivity in Rats with Irritable Bowel Syndrome and Its Mechanism

目的研究5-羟色胺转运体(SERT)与内脏高敏感的联系,探讨中药复方肠吉安对内脏高敏感大鼠的治疗作用及其机制。方法制备肠易激综合征的内脏高敏感模型,将雄性SD大鼠随机分为对照组、模型组、肠吉安高剂量组及肠吉安低剂量组。在造模第10周开始灌胃给药或生理盐水共10天,干预后通过腹肌回缩反射(AWR)半定量评分测定大鼠内脏敏感性;取脑、肠组织,应用Western BIot及real-time PCR方法检测各组织SERT表达;通过免疫组化方法对各组织5-HT进行半定量分析。结果(1)模型组AWR评分显著高于对照组,肠吉安高、低剂量组治疗后评分降低(P<0.05)。(2)模型组结肠、脑中缝背核SERT的mRNA及蛋白表达较对照组显著降低(P<0.05),肠吉安高、低剂量组结肠SERT蛋白表达较模型组显著增加(P<0.05)。(3)模型组结肠5-HT含量明显高于对照组,肠吉安治疗后含量较模型组显著降低(P<0.05),模型组及肠吉安高、低剂量组中缝背核5-HT含量则显著低于对照组(P<0.05)。结论中药复方肠吉安可以通过改变肠道SERT表达及5-HT含量来改善肠易激综合征的内脏高敏感。

Objective To explore the mechanism and efficiency of Changjian （CJA） in treating irritable bowel syndrome through studying the relationship between serotonin transporter （SERT） and visceral hypersensitivity in rats. Methods Male SD rats were randomly divided into 4 groups： the normal control group, the model group, the high-dosage and low-dosage CJA （CJAH and CJAL） groups. Visceral hypersensitivity model was established by eolorectal distension. Normal saline and different doses of CJA were administrated to rats respectively, starting from the 10th day of modeling for 10 days. After then, the abdominal withdrawal reflex （AWR） was scored for semi-quantitative estimation of visceral sensitivity, and tissues of brain and colon were harvested for detecting expressions of SERT and serotonin （5-HT） with Western blot, real-time PCR and immunohistochemistry. Results As compared with the normal controls, in model rats, the AWR score and content of 5-HT in intestinal mucosa were higher （P 〈 0.05 ） , protein and mRNA expressions of SERT in colon and nucleus raphes dorsalis （NRD） were lower （ P 〈 0.05） , but all these indexes were improved significantly after CJA treatment, either in the CJAH or CJAL group （ all P 〈 0.05 ）. Besides, the number of 5-HT energic neuron in the model group and CJA groups was lower than that in the normal control group （P 〈 0.05）. Conclusion CJA has therapeutic effect for improving visceral hypersensitivity in irritable bowel syndrome by way of regulating colonic expression of SERT and content of 5-HT.