Abstract: Objective To observe the effect of Daiyu ointment on angiogenesis and Nrf2 / HO-1 signaling pathway in rats with anal fistula. Method 20 SPF-grade SD rats were constructed a post-operative wound model of fistula by comprehensive method, after successful modeling, they were randomly divided into model group and Daiyu paste group, with 10 rats in each group. Rats in the Daiyu paste group applied the wound with drugs, and the model group scrubbed with 0. 9% sodium chloride solution. In addition, 10 rats with only wounds were selected as the control group, and scrubbed with 0. 9% sodium chloride solution, and the rats in each group were treated twice a day, all of which were continuously intervened for 14 days. then the wound healing and local blood flow was observed. Then the rats were sacrificed. ELISA was used to detect the levels of vascular endothelial growth factor ( VEGF) , VEGF receptor (VEGFR) , epidermal growth factor (EGF) , platelet derived growth factor ( PDGF) , interleukin ( IL) - 1β, IL-6, IL-10, tumor necrosis factor α ( TNF-α) in wound tissues of anal fistula; Western blot was used to detect the protein levels of Nrf2 and HO-1 in the wound tissues. Result Compared with the control group, the wound healing rate and blood flow of the model group significantly decreased ( P < 0. 05) . Compared with the model group, the wound healing rate and blood flow of rats in the Daiyu ointment group significantly increased (P<0. 05) ; Compared with the control group, CD31 positive area significantly decreased (P<0. 05) , while significantly increased in Daiyu ointment group compared with model group; The levels of IL-1β, IL-6, IL-8 and TNF-α in granulation tissue were significantly higher in the model group than in the control group ( P < 0. 05) , and the Daiyu cream group was significantly lower than that in the model group ( P< 0. 05) ; wound tissue VEGF, VEGFR, EGF and PDGF in the model group were significantly higher than those in the control group (P<0. 05) , and the Daiyu ointment group was significantly higher than the model group (P<0. 05) ; the levels of Nrf2 and HO-1 protein in the model group were significantly higher than those in the control group significantly higher (P<0. 05) , and the Daiyu ointment group was significantly higher than the model group ( P< 0. 05) . Conclusion Daiyu ointment can promote the healing of wounds and angiogenesis in anal fistula model rats. The mechanism may be related to the activation of Nrf2 / HO-1 pathway. 

Key words: Nrf2, anal fistula, angiogenesis, Daiyu ointment, HO-1

摘要： 目的 观察黛玉膏对肛瘘大鼠血管生成和 Nrf2 / HO-1 信号通路的影响。 方法 将 20 只 SPF 级 SD 大鼠进行 综合法构建肛瘘术后创面模型,建模成功后随机分为模型组和黛玉膏组,每组 10 只。 黛玉膏组大鼠使用药物涂抹 伤口,模型组以 0. 9%氯化钠溶液擦洗。 另选取 10 只仅造成创口的大鼠作为对照组,也以 0. 9% 氯化钠溶液擦洗, 各组大鼠每天处理 2 次,均连续干预 14 d。 观察创面愈合情况及局部血流。 ELISA 法检测肛瘘创面组织血管内皮 生长因子(VEGF) 、VEGF 受体(VEGFR) 、内皮生长因子(EGF) 、血小板衍生生长因子( PDGF) 、白细胞介素 IL-1β、 IL-6、IL-10、大鼠肿瘤坏死因子 α( TNF-α)水平;Western blot 法检测创面组织 Nrf2 及 HO-1 蛋白水平。 结果 与对 照组相比,模型组创面愈合率及血流量显著下降(P<0. 05) ,与模型组相比黛玉膏组大鼠创面愈合率和血流量显著 升高(P<0. 05);CD31 染色结果比较,模型组较对照组显著降低(P<0. 05),黛玉膏组较模型组显著升高(P<0. 05);肉 芽组织 IL-1β、IL-6、IL-8、TNF-α 比较,模型组较对照组显著升高(P<0. 05),黛玉膏组较模型组显著降低(P<0. 05);肉 芽组织 VEGF、VEGFR、EGF、PDGF 比较,模型组较对照组显著降低 ( P < 0. 05),黛玉膏组较模型组显著升高( P < 0. 05);Nrf2、HO-1 蛋白水平比较,模型组较对照组显著降低(P<0. 05),黛玉膏组较模型组显著升高(P<0. 05)。 结论 黛玉膏可以促进肛瘘模型大鼠创面的愈合,促进肉芽组织的血管新生,其机制可能与激活 Nrf2 / HO-1 通路有关。

关键词: Nrf2, 肛瘘, 血管新生, 黛玉膏, HO-1