黄芪桂枝五物汤对D-半乳糖联合右旋糖酐-40致小鼠衰老皮肤瘙痒模型AQP3的影响

目的:研究黄芪桂枝五物汤治疗老年性皮肤瘙痒症的作用机制。方法:84只SD小鼠随机分为正常组、皮肤衰老组、衰老皮肤瘙痒模型组、苯海拉明组(0.65 mg·kg-1)、黄芪桂枝五物汤低、中、高剂量组(3.25,6.5,13 g·kg-1),每组12只。各组用D-半乳糖125 mg·kg-1连续颈背部ih 42 d,建立皮肤衰老小鼠模型(正常组予生理盐水);实验第7周开始,各用药组分别ig给药,每日1次,连续7 d,其余3组予蒸馏水;造模42 d(ig 7 d)时各组小鼠尾静脉注射右旋糖酐注射液1.25 mg·kg-1,复制出衰老皮肤瘙痒模型(正常组及皮肤衰老组予生理盐水)。造模30 min后,观察黄芪桂枝五物汤对小鼠皮肤瘙痒反应的瘙痒次数及每次持续时间,烘干法测定皮肤含水量,行病理组织学检查观察各组小鼠皮肤皮脂腺、汗腺,免疫组化法检测皮肤及肺脏、肝脏水通道蛋白3(AQP3)总密度值。结果:模型组小鼠皮肤瘙痒次数及每次瘙痒持续时间较皮肤衰老组增多(P0.05),含水量较皮肤衰老组降低(P0.05),皮肤皮脂腺及汗腺数量及分泌较皮肤衰老组增多,皮肤,肺脏及肝脏AQP3表达较皮肤衰老组减少(P0.05);用药后,与模型组比较,各用药组小鼠瘙痒次数及每次瘙痒持续时间明显减少(P0.05),皮肤含水量明显增高(P0.05),皮脂腺及汗腺明显增多,分泌明显增强,各用药组小鼠皮肤,肺脏及肝脏AQP3的表达较模型组升高(P0.05),且黄芪桂枝五物汤低高剂量组较苯海拉明组治疗效果更好(P0.05)。结论:黄芪桂枝五物汤对老年性皮肤瘙痒症有确切的疗效,其作用可能与调节AQP3有关。

Effect of Huangqi Guizhi Wuwu Tang in Treating D-galactose and Low Molecular Dextran-induced Senile Pruritus in Mice

Objective: To study the mechanism of Huangqi Guizhi Wuwu Tang (HGWT) in treating senile pruritus. Method: Totally 84 mice were divided into 7 groups: the normal group, the senile group, the senile pruritus group, the diphenhydramine group (0.65 mg·kg^-1), the low-, middle- and high-dose HGWT groups (3.25, 6.5, 13 g·kg^-1). The senile model was induced in mice by injecting D-galactose at 125 mg·kg^-1 subcutaneously on the nape of the neck for continuous 42 days. The senile pruritus model was induced in mice by adding low molecular dextran at 1.25 mg·kg^-1 intravenously from the 7th week. The mice were intragastrically administered with distilled water in the normal, the senile and the senile pruritus groups, and the others were intragastrically administered with the corresponding medicines once daily for 7 days. The scratching behavior & its lasting time were observed by a digital video camera. The skin's water content was measured by using drying method. Meanwhile, the sebaceous gland and sweat gland were observed by HE staining, the sum density of aquaporin 3 (AQP3) in skin, lung and liver were observed by immunohistochemistry method. Result: Compared with normal and senile groups, the scratching frequency and lasting time increased, the water content decreased, the number and secretion of sebaceous gland and sweat gland increased, and the AQP3 expression in skin, lung and liver decreased in the senile pruritus group (P<0.05). Compared with the senile pruritus group, the scratching frequency and lasting time decreased, the water content increased, the number and secretion of sebaceous gland and sweat gland decreased, and the AQP3 expressions in skin, lung and liver increased in the diphenhydramine and HGWT groups (P<0.05). Moreover, the results were better in the low- and high-dose HGWT groups (P<0.05). Conclusion: HGWT has a definite therapeutic effect in treating senile pruritus and its mechanism may be related to regulating AQP3 expression.