目的 探讨中医温补肾阳法对慢性泄泻大鼠模型结肠黏膜组织水通道蛋白(AQP)8表达和cAMP/cGMP比值的影响.方法 健康雄性Wistar大鼠54只,以随机分配方式,分为正常组、模型组、对照组(蒙脱石散组、参苓白术丸组)和干预组(右归丸高剂量组、右归丸低剂量组),共6组.除正常组外均采用水环境小平台站立法复合高乳糖饲料喂养的方法复制慢性腹泻模型,模型成功后,6组分别给予生理盐水(15 ml/kg)、生理盐水(15 ml/kg)、蒙脱石散溶液(1.0 g/kg)、参苓白术丸溶液(2.4 g/kg)、右归丸高剂量溶液(2.3 g/kg)、右归丸低剂量溶液(1.2 g/kg)灌胃,每天1次,连续给药7 d.取结肠组织,通过免疫组化的方法观察结肠黏膜组织AQP8-mRNA、AQP8、cAMP/cGMP的变化.结果 与正常组比较,模型组大鼠结肠黏膜组织AQP8-mRNA、AQP8、cAMP/cGMP的表达呈"显著降低"的数值反应;相较于模型组,右归丸高剂量组大鼠结肠粘膜组织AQP8-mRNA、AQP8的表达及cAMP/cGMP比值呈"显著提高"之数值反应.右归丸低剂量组和参苓白术丸组可部分提高AQP8-mRNA、AQP8的表达及cAMP/cGMP比值,西药组实验数据改善情况不明显.结论 温补肾阳法(右归丸)可以在慢性腹泻大鼠模型体内充分发挥药效,使cAMP/cGMP比值升高,使大鼠模型结肠黏膜组织中的AQP8-mRNA、AQP8的表达水平提升,致使对水分的吸收作用增强,从而达到止泻的目的.%Objective To explore the effect of therapeutic method with Chinese traditional medicine Wen Bu Shen Yang method on the expression of AQP8 and cAMP/ cGMP ratio in colonic mucosae of chronic diarrhea rat-models. Methods A total of 54 three week-old healthy male rats were randomly divided into six groups:control group,model group,matched groups (west medicine group and Shen Lin Bai Shu Wan group),intervention groups (high dosage You Gui Wan group and low dosage You Gui Wan group). Rats in model group and treatment groups were given with high amount of lactose diet,and they were forced to stand on the multiple platform which was full of water around to establish the type of spleen deficiency diarrhea. Then,the drug was given once a day for 7 days. In this procedure,these rats were given with normal saline (15 ml/ kg),normal saline (15 ml/ kg),montmorillonite dispersant solution (1. 0 g/ kg),pulverization solution of Shen Lin Bai Shu Wan (2. 4 g/kg),high dosage pulverization solution of You Gui Wan (2. 3 g/ kg),and low dosage pulverization solution of You Gui Wan (1. 2 g/ kg)respec-tively. Then the changes in expression of AQP8 and cAMP/ cGMP ratio in colon mucosae were measured by the immunohistochemical method. Re-sults The expression of AQP8 and cAMP/ cGMP ratio in model group was significantly decreased in comparison with those of control group. In comparison with model group,the expression of AQP8 and cAMP/ cGMP ratio in all treatment groups was significantly increased,therefore the manifestation of high dosage You Gui Wan group was highlighted,low dosage You Gui Wan group and Shen Lin Bai Shu Wan group were the sec-ond,and west medicine group was unconspicuous. Conclusion The method of Wen Bu Shen Yang therapy (You Gui Wan)can plenarily exert pesticide effect in rat-models,it may be via the way of increasing the cAMP/ cGMP ratio. Its action of anti-diarrhea may be via the way of in-creasing the expression of AQP8 protein to adjust the absorption of water in colonic mucosae of model rats with chronic diarrhea.
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