| 引用本文: |
黎秀秀, 刘灿, 谢天乐, 吴雨笛, 谭莘巍, 谭静, 常小荣.艾灸对胃癌大鼠肿瘤血管正常化时间窗的影响[J].湖南中医药大学学报,2026,46(2):297-304[点击复制] |
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| 艾灸对胃癌大鼠肿瘤血管正常化时间窗的影响 |
| 黎秀秀,刘灿,谢天乐,吴雨笛,谭莘巍,谭静,常小荣 |
| (湖南中医药大学针灸推拿与康复学院, 湖南 长沙 410208) |
| 摘要: |
| 目的 观察艾灸对胃癌（GC）大鼠肿瘤血管正常化的促进作用及动态变化规律，为艾灸辅助胃癌治疗提供新参考。方法 采用Walker256瘤块胃部移植法构建GC大鼠模型，研究分两个阶段进行。第一阶段：将造模成功的24只大鼠随机分为模型组、艾灸组、贝伐单抗组，每组8只。模型组不干预；艾灸组隔天交替悬灸两组穴位（中脘、关元、足三里；脾俞、胃俞），每次20 min，每天1次，连续21 d；贝伐单抗组每4 天尾静脉注射贝伐单抗5 mg/kg，21 d内共5次。期间密切观察各组大鼠的生存状态、不良反应，每隔2天利用光声成像检测肿瘤组织血氧饱和度（SO2），明确血管正常化时间窗开始（t始）、高峰（t峰）、结束（t末）3个时间节点。第二阶段：将造模成功的140只大鼠分为模型组、艾灸组、贝伐单抗组，每组再设t始、t峰、t末3个亚组，每个亚组14只，造模及干预方法同第一阶段，各组在对应时间点处死动物取材，采用透射电镜、免疫荧光观测肿瘤组织血管内皮细胞形态、血小板内皮细胞黏附分子-1（CD31）、α-平滑肌肌动蛋白(α-SMA)改变，同时采用伊文思蓝染色观测肿瘤组织血管渗透功能变化。结果 治疗期间，艾灸组大鼠2例发生皮肤意外烫伤，贝伐单抗组大鼠3例鼻牙龈出血、1例肠道出血、1例左后肢偏瘫。生存状态上，干预15~21 d时，艾灸组、贝伐单抗组生存状态积分均高于模型组（P＜0.05），同时艾灸组高于贝伐单抗组（P＜0.05）。光声成像检测SO2显示，艾灸组肿瘤血管正常化窗口期为干预13～19 d（时间窗共计7 d，t始为13 d、t峰为17 d、t末为19 d），贝伐单抗组为干预13～17 d（时间窗共计5 d，t始为13 d、t峰为15 d、t末为17 d），艾灸组t峰（17 d）时SO2含量明显高于贝伐单抗组（P＜0.01）。与模型组比较，艾灸及贝伐单抗组在t始时各项指标比较差异无统计学意义（P＞0.05）；在t峰、t末时，血管内皮细胞形态、基底膜厚度及连续性改善，CD31表达、伊文思蓝浓度降低（P＜0.01），α-SMA表达增高（P＜0.05，P＜0.01）。与贝伐单抗组比较，艾灸组α-SMA表达水平稍低，CD31表达、伊文思蓝浓度稍高，但差异均无统计学意义（P＞0.05）。结论 艾灸及贝伐单抗治疗均能有效促进胃癌大鼠肿瘤血管正常化，两组对血管结构与功能的改善未见明显差异，但艾灸作用的血管正常化时间窗更长，对生存状态的改善更佳。 |
| 关键词: 胃癌 艾灸 贝伐单抗 肿瘤血管正常化 时间窗 肿瘤微环境 |
| DOI：10.3969/j.issn.1674-070X.2026.02.010 |
| 投稿时间：2025-10-15 |
| 基金项目:国家自然科学基金青年项目(82205296)。 |
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| Effects of moxibustion on the normalization time window of tumor vessel in rats with gastric cancer |
| LI Xiuxiu, LIU Can, XIE Tianle, WU Yudi, TAN Shenwei, TAN Jing, CHANG Xiaorong |
| (School of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To observe the promotive effects and dynamic patterns of moxibustion on the normalization of tumor blood vessels in rats with gastric cancer (GC), and to provide a novel reference for moxibustion as a complementary therapy for gastric cancer. Methods A GC rat model was established via gastric transplantation of Walker-256 tumor fragments. The study was conducted in two phases. Phase I:Twenty-four rats with successful modeling were randomized into the model group, moxibustion group, and bevacizumab groups (n=8 per group). The model group received no intervention. The moxibustion group received suspended moxibustion at two alternating sets of acupoints[Zhongwan (CV 12), Guanyuan (CV 4), Zusanli (ST 36); Pishu (BL 20), Weishu (BL 21)] for 20 min once daily for 21 consecutive days. The bevacizumab group received tail vein injections of bevacizumab (5 mg/kg) every 4 days for a total of 5 times within 21 days. During this period, survival status and adverse reactions of rats were observed. Oxygen saturation (SO2) within the tumor was monitored every two days using photoacoustic imaging to identify three time points:the onset (tstart), peak (tpeak), and end (tend) of the vascular normalization window. Phase II:the 140 successful modeled rats were divided into model group, moxibustion group, and bevacizumab group. Each group was further subdivided into tstart, tpeak, and tend subgroups (n=14 per subgroup). The modeling and intervention methods were the same as those in the first phase. Rats in each group were sacrificed at the corresponding time points for sample collection. The morphology of vascular endothelial cells in tumor tissues, the changes of platelet endothelial cell adhesion molecule-1 (CD31) and α-smooth muscle actin (α-SMA) were observed by transmission electron microscopy and immunofluorescence. Meanwhile, Evans blue staining was used to observe the changes of vascular permeation function in tumor tissues. Results During the treatment period, two rats in moxibustion group had accidental skin burns, while three rats in bevacizumab group had epistaxis and gingival bleeding, and one had intestinal bleeding, and one had hemiplegia of the left hind limb. In terms of survival status, at 15-21 days of intervention, survival scores in both the moxibustion group and bevacizumab groups were significantly higher than those in the model group (P<0.05), and moxibustion group outperformed the bevacizumab group (P<0.05). Photoacoustic imaging showed that the normalization window for moxibustion group lasted 7 days (day 13-19; tstart=13 d, tpeak=17 d, tend=19 d), while the bevacizumab group lasted 5 days (day 13-17; tstart=13 d, tpeak=15 d, tend=17 d). The SO2 level at tpeak (17 d) was significantly higher in moxibustion group than in the bevacizumab group (P<0.01). Compared with the model group, there was no statistically significant difference in each index at tstart between the moxibustion and bevacizumab groups (P>0.05). At tpeak and tend, both interventions improved endothelial morphology and basement membrane integrity, decreased CD31 expression and Evans blue concentration (P<0.01), and increased α-SMA expression (P<0.05, P<0.01) compared to model group. Compared with the bevacizumab group, moxibustion group showed slightly lower α-SMA expression and slightly higher CD31 expression and Evans blue concentration, though these differences were not statistically significant (P>0.05). Conclusion Both moxibustion and bevacizumab treatment effectively promote tumor vascular normalization in rats with GC. While the two interventions show no significant difference in improving vascular structure and function, moxibustion induces a longer normalization window and provides superior benefits in improving survival status. |
| Key words: gastric cancer moxibustion bevacizumab tumor vascular normalization time window tumor microenvironment |
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