首页|左金方靶向特洛细胞抗胃癌的作用机制研究

左金方靶向特洛细胞抗胃癌的作用机制研究

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目的 探究特洛细胞(TCs)作为左金方抗胃癌作用的潜在靶标。方法 建立N-甲基-N'-硝基-N-亚硝基胍(MNNG)联合幽门螺旋杆菌(Helicobacter pylori,H。pylori)的小鼠胃癌动物模型,模型成功后将小鼠分为模型组和左金方高、中、低剂量(1。456、0。728、0。364 g·kg-1)组,对照组不造模。每天ig给药1次,对照组、模型组给予等体积水。第38周收集小鼠胃组织标本,应用透射电子显微镜(TEM)、免疫组化、多重荧光免疫组化(mFIHC)技术对小鼠胃正常组织中TCs的形态、分布及免疫表型进行分析;苏木素-伊红(HE)检测各组小鼠胃病理改变;TEM观察各组小鼠胃中TCs的形态变化;mFIHC检测各组小鼠胃组织中TCs的数量。结果 小鼠胃正常组织中,黏膜层TCs数量较少,黏膜下层和肌层中TCs相对较多,TCs的胞体呈长梭形或纺锤形,具有细长伴节状膨大的端足(Tps),与血管、神经和平滑肌伴行交联,形成网状结构;免疫表型为CD34+/PDGFR-α+/CD31-/c-kit-,与人胃组织中的一致。与对照组比较,小鼠胃癌组织中,TCs的形态发生改变,网状结构缺失,分布密度显著下降,数量显著减少(P<0。01);与模型组相比,左金方组均能改善TCs的变化,高剂量组明显减轻了胃组织的病理损伤,TCs的形态和网状结构逐渐恢复,数量回升,差异有统计学意义(P<0。01)。结论 TCs在小鼠胃组织各层均有分布,其免疫表型为CD34+/PDGFR-α+/CD31-/c-kit-,逆转TCs的缺失可能是左金方抗胃癌作用的重要机制。
Research on mechanism of Zuojin Fang targeting telocytes in anti-gastric cancer
Objective To explore the potential role of telocytes(TCs)as a target for the anti-gastric cancer effect of Zuojin Fang.Methods A mouse gastric cancer animal model was established using N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)combined with H.pylori.After successful modeling,the mice were divided into model group and Zuojin Fang high,medium,and low dose(1.456,0.728,0.364 g·kg-1)groups,while the control group was not modeled.Administered ig once a day,and gave equal volumes of water to the control group and model group.Collected mouse stomach tissue specimens in week 38,selected mouse gastric tissue samples were analyzed using transmission electron microscopy(TEM),immunohistochemistry,and multiplex fluorescence immunohistochemistry to study the morphology,distribution,and immunophenotype of TCs in normal gastric tissue.Hematoxylin eosin(HE)was used to detect the pathological changes in the stomach of mice in each group,TEM observation of the morphological changes of TCs in the stomachs of mice in each group,mFIHC was used to detect the number of TCs cells in the gastric tissue of mice in each group.Results In normal mouse gastric tissue,fewer TCs were found in the mucosal layer,while TCs were relatively more abundant in the submucosal and muscular layers.The cell bodies of TCs were spindle-shaped or fusiform,with long,slender,and beaded Tps,associating with blood vessels,nerves,and smooth muscle,forming a reticular structure.The immunophenotype was CD34+/PDGFR-α+/c-kit-/CD31-,consistent with that in human gastric tissue.In mouse gastric cancer tissue,the morphology of TCs changed,the reticular structure was lost,the distribution density significantly decreased,and the number significantly reduced(P<0.01).Compared with the model group,the Zuojin Fang groups were able to improve the changes in TCs.The high-dose group notably reduced the pathological damage to gastric tissue,and the morphology and reticular structure of TCs gradually recovered,with the number increased,showing a statistically significant difference(P<0.01).Conclusion TCs are distributed in all layers of mouse gastric tissue,with an immunophenotype of CD34+/PDGFR-α+/c-kit-/CD31-.The reduction of TCs may be an important mechanism for the anti-gastric cancer effect of Zuo Jin Fang.

telocytesgastric cancerZuojin Fangtarget

陈子平、何勇、黄庆宝、杨舒乔、胡巨豪、余惠旻、周红祖

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深圳大学医学部,广东 深圳 518060

深圳大学总医院,广东 深圳 518060

广州中医药大学第四临床医学院深圳市中医院,广东 深圳 518033

telocytes 胃癌 左金方 靶标

2024

药物评价研究
天津药物研究院 中国药学会

药物评价研究

CSTPCD北大核心
影响因子:1.199
ISSN:1674-6376
年,卷(期):2024.47(12)