黄芪桂枝五物汤不同给药途径对冻伤模型大鼠的影响及其作用机制

目的：研究黄芪桂枝五物汤不同给药途径对冻伤模型大鼠的作用及其机制。 方法：采用低温乙醇和水混合浸泡法制备大鼠冻伤模型，测定模型大鼠及黄芪桂枝五物汤口服、浸泡、口服加浸泡3种不同给药途径治疗后部分免疫细胞因子和血栓戊烷B2（thromboxane B2，TXB2）、6-酮-前列腺素F1α（6-keto-prostaglandin F1α，6-keto-PGF1α）的变化。 结果：与正常对照组相比，模型大鼠血清白细胞介素6（interleukin-6，IL-6）、肿瘤坏死因子β（tumor necrosis factor-β，TNF-β）、TXB2含量均显著升高（P〈0.01），6-keto-PGF1α含量显著降低（P〈0.01）。与模型组相比，口服黄芪桂枝五物汤可显著降低IL-6的含量（P〈0.05），浸泡黄芪桂枝五物汤对血清IL-6含量无显著的降低作用（P〉0.05），两种给药方式对IL-6的影响无交互作用（P〉0.05）；口服组、浸泡组TNF-β含量均显著降低（P〈0.01，P〈0.05），两种给药方式对TNF-β的影响有交互作用（P〈0.05）。口服、浸泡黄芪桂枝五物汤对TXB2含量无降低作用（P〉0.05），两种给药方式对TXB2的影响无交互作用（P〉0.05）；口服黄芪桂枝五物汤可使6-keto-PGF1α的含量显著升高（P〈0.01），浸泡黄芪桂枝五物汤对6-keto-PGF1α含量无明显影响（P〉0.05），两种给药方式对6-keto-PGF1α的影响有交互作用（P〈0.05）。 结论：冻伤模型大鼠存在免疫应激和血栓易形成状态，口服加浸泡黄芪桂枝五物汤对冻伤局部的改善较明显，其机制可能是通过调节冻伤大鼠免疫功能和TXB2-PGF1α失衡而起作用。

Effects of Huangqi Guizhi Wuwu Decoction given by different administration methods on rats with frostbite and the mechanism

Objective： To establish a rat model of frostbite and to evaluate the effects of different administration methods of Huangqi Guizhi Wuwu Decoction （HGWD）, a compound traditional Chinese herbal medicine for warming meridians to disperse cold, on rats with frostbite.
Methods： Frostbite in rats was induced by the method of soaking feet in hypothermia ethanol-water mixture. Levels of interleukin-6 （IL-6）, tumor necrosis factor-β （TNF-β）, thromboxane B2 （TXB2） and 6-keto-prostaglandin F1α （6-keto-PGF1α） in serum of rats treated with different administration methods of HGWD, such as oral administration （Oral HGWD）, soak （Soak HGWD）, and oral administration plus soak （Oral-soak HGWD）, were tested by enzyme-linked immunosorbent assay.
Results： IL-6, TNF-β, TXB2 levels were significantly higher （P〈0.01） and 6-keto-PGF1α level was lower （P〈0.01） in serum of rats in the untreated group than in the normal control group. Compared with the untreated group, the level of IL-6 obviously decreased （P〈0.05） in serum of the rats treated by oral HGWD, while no significant decrease （P〉0.05） was observed in the soak HGWD group, and there was no interaction （P〉0.05） between the two administration methods in regulating the level of IL-6. The levels of TNF-β obviously decreased （P〈0.01, P〈0.05） in serum of the rats treated by oral and soak HGWD, and there was interaction between the two administration methods. The level of TNF-β in the oral HGWD group was significantly lower than that in the soak HGWD group （P〈0.01）. Compared with the untreated group, level of TXB2 in oral HGWD or soak HGWD group did not decrease significantly （P〉0.05） and there was no interaction （P〉0.05） between the two administration methods. The level of 6-keto-PGF1α was obviously increased （P〈0.01） in serum of the rats treated by oral HGWD, while there was no significant decrease （P〉0.05） in the soak HGWD group as compared with the untreated group, and there was interaction （P〈0.05） between the two administration methods in regulating the level of 6-keto-PGF1α.
Conclusion： Rats with frostbite has immunologic dysfunction and a state of forming thrombus easily. The oral-soak HGWD can improve frostbite of local skin in rats. The therapeutic mechanism of HGWD may be to regulate the dysfunction of immune system and the imbalance of TXB2-PGF1α.