桃红四物汤调控PI3K/Akt通路促进吻合血管存活*

作者：袁率财，孙绍裘，李益亮，何梦帆，曾祥晶，黄 臻，刘 威，姚金龙

单位：湖南中医药大学第二附属医院，湖南 长沙 410005

引用：引用：袁率财，孙绍裘，李益亮，何梦帆，曾祥晶，黄臻，刘威，姚金龙.桃红四物汤调控PI3K/Akt通路促进吻合血管存活[J].中医药导报,2026,32(3):18-25.

DOI：10.13862/j.cn43-1446/r.2026.03.004

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摘要：

目的：基于网络药理学与分子对接技术探讨桃红四物汤调控吻合血管存活的分子机制，并通过动物实验验证其关键信号通路。方法：基于中药系统药理学数据库与分析平台（TCMSP）数据库筛选桃红四物汤活性成分及靶点，结合血管吻合相关靶点获取93个交集基因，构建PPI网络筛选28个核心靶点，通过京都基因与基因组百科全书（KEGG）/基因本体（GO）富集分析锁定PI3K/Akt为核心通路；通过分子对接明确β-谷甾醇、槲皮素、木犀草素与PI3K/Akt通路蛋白的结合能力；最后，建立大鼠尾部中动脉吻合模型，随机分为假手术组、空白组、桃红四物汤组及蒸馏水组（n=9），术后分别灌胃干预，于第2、8、15天苏木精-伊红（HE）染色检测血管内膜面积，蛋白质印迹（Western blotting）法检测PI3K/Akt通路及VEGF蛋白表达。结果：网络药理学预测桃红四物汤可能通过PI3K/Akt通路调控吻合血管存活，分子对接示β-谷甾醇、槲皮素、木犀草素与PI3K/Akt通路蛋白具有强结合能力；术后第1天，桃红四物汤组与蒸馏水组大鼠尾部血管充盈时间于术后第1天就达到峰值，并逐步于第6~7天恢复至正常水平，空白组与假手术组未进行血管吻合大鼠尾部血管充盈时间无明显差异；HE染色显示：干预第2天，桃红四物汤组血管内膜面积与其他组比较，差异有统计学意义（P<0.05）。Western Blotting结果显示，桃红四物汤组在术后第2天即显著上调VEGF、PI3K及Akt蛋白表达；至第8天，该组VEGF（P<0.05）、PI3K（P<0.05）及Akt（P<0.01）表达仍显著高于蒸馏水组；第15天时，桃红四物汤组PI3K（P<0.05）及Akt（P<0.01）表达仍显著高于蒸馏水组。结论：桃红四物汤可能通过促进PI3K/Akt信号轴相关蛋白表达，推动吻合血管存活。

关键词：桃红四物汤；吻合血管；血管再生；PI3K/Akt信号通路；网络药理学；大鼠

Abstract：

Objective: To investigate the molecular mechanism by which Taohong Siwu Decoction (THSWD) promotes vascular anastomosis survival using network pharmacology and molecular docking, and to validate the key signaling pathway through animal experiments. Methods: Active components and corresponding targets of THSWD were screened from the TCMSP database. By intersecting with vascular anastomosis-related targets, 93 overlapping genes were obtained. A protein-protein interaction (PPI) network was constructed to identify 28 core targets. KEGG and GO enrichment analyses pinpointed the PI3K/Akt pathway as a key pathway. Molecular docking was performed to evaluate the binding affinities of β-sitosterol, quercetin, and luteolin with PI3K/Akt pathway proteins. Finally, a rat tail artery anastomosis model was established. The rats were randomly divided into sham-operated group, blank group, THSWD group, and distilled water group (n=9). Postoperative interventions were administered by gavage. On days 2, 8, and 15 post-surgery, HE staining was used to measure the vascular intimal area, and Western blotting was used to detect the expression of PI3K/Akt pathway proteins and VEGF. Results: Network pharmacology predicted that THSWD might regulate vascular anastomosis survival through the PI3K/Akt pathway. Molecular docking indicated strong binding affinities of β-sitosterol, quercetin, and luteolin with PI3K/Akt pathway proteins. On postoperative day 1, the tail vascular filling time in both the THSWD group and the distilled water group peaked and then gradually returned to normal levels by days 6-7. There was no significant difference in tail vascular filling time between the blank group and the sham-operated group (rats without vascular anastomosis). HE staining showed that on day 2 of intervention, the vascular intimal area in the THSWD group was significantly different compared to the other groups (P<0.05). Western blotting results showed that the THSWD group exhibited significantly up-regulated protein expression of VEGF, PI3K, and Akt as early as day 2 post-surgery. By day 8, the expression levels of VEGF (P<0.05), PI3K (P<0.05), and Akt (P<0.01) in this group remained significantly higher than those in the distilled water group. On day 15, the expression of PI3K (P<0.05) and Akt (P<0.01) in the THSWD group was still significantly elevated compared to the distilled water group. Conclusion: Taohong Siwu Decoction may promote vascular anastomosis survival by up-regulating the expression of proteins in the PI3K/Akt signaling axis.

Key words：Taohong Siwu Decoction; vascular anastomosis; angiogenesis; PI3K/Akt signaling pathway; network pharmacology; rats

发布时间：2026-03-28

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