【目的】探讨益气通窍方对鼻咽癌裸鼠的治疗作用及机制。 【方法】将32只裸鼠随机分为正常组，模型组及益气通窍方 低、高剂量组，每组8只。除正常组外，其余各组裸鼠构建鼻咽癌模型。治疗结束后，测量裸鼠瘤体体积，采用酶联免疫吸 附分析 （ELISA） 检测血清转化生长因子β1 （TGF-β1） 、血管内皮细胞生长因子 （VEGF） 水平，苏木素-伊红 （HE） 染色法观察鼻 黏膜组织病理形态，定量聚合酶链反应 （PCR） 法检测鼻黏膜组织基质金属蛋白酶组织抑制剂1 （TIMP-1） 、基质金属蛋白酶9 （MMP-9） 的mRNA表达，蛋白免疫印迹 （Western Blot） 法检测鼻黏膜组织Wnt-1、β-连环蛋白 （β-catenin） 蛋白表达。 【结果】 与正常组比较，模型组裸鼠瘤体体积增大，血清TGF-β1、VEGF水平升高，鼻黏膜组织TIMP-1 mRNA表达水平降低、 MMP-9 mRNA表达水平升高，鼻黏膜组织Wnt-1、β-catenin蛋白表达水平升高 （均P＜0.05） ，HE染色可见鼻黏膜结构缺损， 大量嗜酸性粒细胞及其他炎性细胞浸润；与模型组比较，益气通窍方低、高剂量组裸鼠瘤体体积缩小，血清TGF-β1、 VEGF水平降低，鼻黏膜组织TIMP-1 mRNA表达水平升高、MMP-9 mRNA表达水平降低，鼻黏膜组织Wnt-1、β-catenin蛋 白表达水平降低 （均P＜0.05） ，呈剂量依赖性，HE染色可见鼻黏膜细胞形态明显改善。 【结论】益气通窍方通过TIMP-1的内 源性调节作用抑制MMP-9活性，维持鼻咽癌细胞外基质稳态，通过抑制Wnt/β-catenin信号通路的异常激活，减少TGF-β1、 VEGF释放，减少肿瘤血管生成，进而实现对鼻咽癌裸鼠的抑瘤作用。

Objective To investigate the therapeutic effect and mechanism of Yiqi Tongqiao Prescription on nasopharyngeal carcinoma in nude mice. Methods Thirty-two nude mice were randomly divided into normal group， model group，Yiqi Tongqiao Prescription low- and high- dose groups，with eight mice in each group. Except for the normal group，the other groups of nude mice were used to construct a nasopharyngeal carcinoma model. After treatment，the tumor volume of nude mice was measured，the levels of serum transforming growth factor β1 （TGF-β1） and vascular endothelial growth factor（VEGF） were detected by enzyme-linked immunosorbent assay （ELISA）， the pathological morphology of nasal mucosa was observed by hematoxylin-eosin （HE） staining， the mRNA expressions of tissue inhibitor of metalloproteinase 1 （TIMP-1） and matrix metalloproteinase 9 （MMP-9） in nasal mucosa were detected by quantitative polymerase chain reaction（PCR），the protein expressions of Wnt-1 and β-catenin in nasal mucosa were detected by Western Blot. Results Compared with the normal group，the tumor volume of nude mice in the model group was increased，the levels of serum TGF-β1 and VEGF were increased， the mRNA expression level of TIMP-1 in nasal mucosa was decreased，the mRNA expression level of MMP-9 was increased，and the protein expression levels of Wnt-1 and β-catenin in nasal mucosa were increased （all P＜ 0.05） . HE staining results showed structural defects of nasal mucosa，and a large number of eosinophils and other inflammatory cell infiltration. Compared with the model group，the tumor volume of nude mice in the low- and high- dose groups of Yiqi Tongqiao Prescription was reduced，the levels of serum TGF- β1 and VEGF were decreased，the mRNA expression level of TIMP-1 in nasal mucosa was increased，the mRNA expression level of MMP-9 was decreased，and the protein expression levels of Wnt-1 and β-catenin in nasal mucosa were decreased （all P＜0.05） in a dose-dependent manner. HE staining results showed that the morphology of nasal mucosa cells was significantly improved. Conclusion Yiqi Tongqiao Prescription inhibits the activity of MMP-9 through the endogenous regulation of TIMP-1 to maintain the homeostasis of extracellular matrix in nasopharyngeal carcinoma， and inhibits the abnormal activation of Wnt/β-catenin signaling pathway and reduces the release of TGF-β1 and VEGF to reduce tumor angiogenesis，thereby playing a role in tumor inhibition for nude mice with nasopharyngeal carcinoma.

R285.5

国家自然科学基金委员会资助项目 （编号：81874495）