目的 探讨复元活血汤联合阿托伐他汀对大鼠原位回植皮瓣血管形成及远端供血的影响。方法 将 40 只 SD 大鼠随机分为对照组、复元活血汤组（7.14 g·kg-1 ）、阿托伐他汀组（20 mg·kg-1 ）、复元活血汤联合阿托伐他 汀组（复原元活血汤 7.14 g·kg-1 +阿托伐他汀钙片 20 mg·kg-1 ），每组 10 只。采用手术方式对各组大鼠构建背部 超长随意皮瓣模型，在大鼠背部分离大小为 2 cm × 8 cm 的皮瓣，并将皮瓣原位缝合。各给药组大鼠灌胃给 药，每天 1 次，连续 7 d，对照组灌胃等量生理盐水。7 d 后分析计算大鼠皮瓣组织成活率；采用 HE 染色法观 察皮瓣组织病理变化；免疫组化法检测皮瓣组织中 CD34 的表达水平；ELISA 法检测皮瓣组织中白细胞介素 6（IL-6）、肿瘤坏死因子 α（TNF-α）含量；RT-qPCR 及 Western Blot 法检测皮瓣组织中蛋白激酶 D1（PKD1）、 组蛋白去乙酰化酶 5（HDAC5）、血管内皮生长因子（VEGF）mRNA 及蛋白表达水平。结果 与对照组比较，各 给药组大鼠的皮瓣成活面积均明显增大（P＜0.05），皮瓣成活率明显升高（P＜0.05）；皮瓣组织中的中性粒细胞 数量均明显减少（P＜0.05），CD34 表达水平均明显升高（P＜0.05），IL-6、TNF-α 水平明显降低（P＜0.05）；皮 瓣组织中 PKD1、HDAC5、VEGF mRNA 及蛋白表达均明显上调（P＜0.05）。与复元活血汤组或阿托伐他汀组 比较，复元活血汤联合阿托伐他汀组的大鼠皮瓣成活面积明显增大（P＜0.05），皮瓣成活率明显升高（P＜ 0.05）；皮瓣组织中的中性粒细胞数量明显减少（P＜0.05），CD34 表达水平明显升高（P＜0.05），IL-6、TNF-α 水平明显降低（P＜0.05）；皮瓣组织中 PKD1、HDAC5、VEGF mRNA 或蛋白表达均明显上调（P＜0.05）。 结论 复元活血汤与阿托伐他汀联用能促进大鼠皮瓣原位回植后的血管形成，改善皮瓣微循环，促进远端供 血，且效果优于单用组，可能与激活 PKD1/HDAC5/VEGF 通路有关。

Objective To investigate the effect of Fuyuan Huoxue Decoction combined with Atorvastatin on vascular formation and distal blood supply in rat orthotopic replanted skin flaps. Methods Forty rats were randomly divided into a control group，a Fuyuan Huoxue Decoction group （7.14 g·kg-1 ），an Atorvastatin group （20 mg·kg-1 ），and a Fuyuan Huoxue Decoction combined with Atorvastatin group （Fuyuan Huoxue Decoction 7.14 g·kg-1 + Atorvastatin Calcium Tablets 20 mg·kg-1 ），with 10 rats in each group. A dorsal super-long random skin flap model was constructed in each group by surgical method，and a skin flap of 2 cm × 8 cm was separated on the rat’s back and sutured in situ. The rats in each treatment group were given intragastric administration once a day for 7 consecutive days，while the control group was given the same amount of normal saline. After 7 days，the survival rate of the skin flap tissue was analyzed and calculated；the pathological changes of the skin flap tissue were observed by HE staining；the expression level of CD34 in the skin flap tissue was detected by immunohistochemistry；the levels of interleukin-6（IL-6） and tumor necrosis factor-α（TNF-α） in the skin flap tissue were detected by ELISA；the mRNA and protein expression levels of protein kinase D1（PKD1），histone deacetylase 5（HDAC5），and vascular endothelial growth factor （VEGF） in the skin flap tissue were detected by RT-qPCR and Western Blot. Results Compared with the control group，the survival area of the skin flaps in each treatment group was significantly increased （P＜0.05），and the survival rate of the skin flaps was significantly increased （P＜0.05）；the number of neutrophils in the skin flap tissue was significantly reduced （P＜ 0.05），the expression level of CD34 was significantly increased （P＜0.05），and the levels of IL-6 and TNF-α were significantly decreased （P＜0.05）；the mRNA and protein expressions of PKD1，HDAC5，and VEGF in the skin flap tissue were significantly up-regulated （P＜0.05）. Compared with the Fuyuan Huoxue Decoction group or the Atorvastatin group，the survival area of the skin flaps in the Fuyuan Huoxue Decoction combined with Atorvastatin group was significantly increased （P＜0.05），and the survival rate of the skin flaps was significantly increased （P＜0.05）； the number of neutrophils in the skin flap tissue was significantly reduced （P＜0.05），the expression level of CD34 was significantly increased （P＜0.05），and the levels of IL-6 and TNF-α were significantly decreased （P＜0.05）；the mRNA and protein expressions of PKD1，HDAC5，and VEGF in the skin flap tissue were significantly up-regulated （P＜0.05）. Conclusion The combination of Fuyuan Huoxue Decoction and Atorvastatin can promote vascular formation， improve microcirculation，and enhance distal blood supply in rat orthotopic replanted skin flaps，with effects superior to those of the single treatment groups，which may be related to the activation of the PKD1/HDAC5/VEGF pathway.

R285.5

四川省科技厅项目（2022JDKP0051）；泸州市科技计划项目（2019-SYF-40）。