痛泻要方抗炎镇痛止泻作用及对PGE2-cAMP信号通路影响.docVIP

痛泻要方抗炎镇痛止泻作用及对PGE2/cAMP信号通路影响 　【摘要】 目的探讨痛泻要方的抗炎镇痛作用机制。方法采用二甲苯致小鼠耳肿胀法观察抗炎作用;采用酶联免疫法测定冰醋酸致痛小鼠血清中前列腺素E2(PGE2)和环磷酸腺苷(cAMP)的浓度;采用大黄致泻法观察止泻作用。结果痛泻要方对二甲苯致小鼠耳肿胀、对冰醋酸致痛小鼠均有显著抑制作用;并明显降低冰醋酸致痛小鼠血清中PGE2和cAMP浓度;能延长小鼠排黑粪的潜伏期，明显减少黑粪排出数量。结论痛泻要方具有良好抗炎镇痛止泻作用，PGE2/cAMP信号通路参与了痛泻要方的抗炎镇痛作用。 【关键词】 痛泻要方; 抗炎镇痛止泻; PGE2/cAMP信号通路 　　Abstract：ObjectiveTo study anti-inflammatory, analgesic and anti-diarrhea mechanism of Tongxie Yaofang. Methods The dimethylbenzene-caused swelling of mouse ear was used to observe the anti-inflammatory effect. Enzymelinked immunosorbent assay was used to measure the PGE2 and cAMP levels in serum of aceticacid-induced pain mice. The rhubarb-induced diarrhea was used to observe the anti-diarrhea effect. ResultsThe anti-inflammatory effect on the swelling of mouse ear caused by dimethylbenzene and the anti-diarrhea effect on the rhubarb-induced diarrhea was significant. The PGE2 and cAMP concentration in blood serum of acetic-acid-induced pain mice was significantly reduced. The delitescence of the mouse’s morbus niger excretion was prolonged, and the quantity of the excretion was significantly decreased.ConclusionTongxie Yaofang has significant anti-inflammatory, antipain and anti-diarrhea effects, and PGE2/cAMP signal pathway participates in the anti-inflammatory, analgesic effects. 　　Key words：Tongxie Yaofang; Anti-inflammatory; Antipain and anti-diarrhea; PGE2/cAMP signal path 　　痛泻要方是治疗痛泻之症的传统方剂，由白术、白芍、陈皮和防风组成，《丹溪心法》和《景岳全书》都有记载，具有健脾舒肝、止痛止泻的作用，主治腹痛腹泻、肠鸣腹痛、大便泄泻等。目前多用于溃疡性结肠炎和肠易激综合症的腹痛等症的治疗[1]，但其抗炎镇痛作用机制尚不清楚。有文献研究表明，前列腺素E2(prostaglandin E2，PGE2)在疼痛的发生中起着重要的作用[2，3]，而疼痛和痛觉过敏是组织损伤或炎症时常伴有的生理病理过程，谷氨酸、P物质等神经递质或神经肽以及细胞内的信号转导途径参与此过程， 3’，5’-环磷酸腺苷(cyclic adenosine monophosphate，cAMP)是最早发现的第二信使，也是cAMP信号转导系统中的关键环节，并对某些神经递质起调节作用[4，5]。因此，本实验采用对二甲苯致小鼠耳肿胀法和生大黄致腹泻法观察痛泻要方的抗炎止泻作用，并测定冰醋酸致痛小鼠血清中PGE2和cAMP的浓度，进一步探讨痛泻要方的抗炎镇痛作用机制。 　　1 材料与仪器 　　1.1 动物与分组 SPF级NIH小鼠，体质量18～22 g，动物合格证号2008A023，购自广东省医学实验动物中心。随机分为5组：模型对照组，阳性对照组(盐酸小檗碱)，痛泻要方低、中、高剂量组(11.8，23.6，47.2 g生药量·kg-1;相当与成人2，4，8倍等效剂量)。 　　1.2 试药与仪