[關(guān)鍵詞]
[摘要]
目的 探究特洛細胞(TCs)作為左金方抗胃癌作用的潛在靶標。方法 建立N-甲基-N'-硝基-N-亞硝基胍(MNNG)聯(lián)合幽門螺旋桿菌(Helicobacter pylori,H.pylori)的小鼠胃癌動物模型,模型成功后將小鼠分為模型組和左金方高、中、低劑量(1.456、0.728、0.364 g·kg-1)組,對照組不造模。每天ig給藥1次,對照組、模型組給予等體積水。第38周收集小鼠胃組織標本,應(yīng)用透射電子顯微鏡(TEM)、免疫組化、多重?zé)晒饷庖呓M化(mFIHC)技術(shù)對小鼠胃正常組織中TCs的形態(tài)、分布及免疫表型進行分析;蘇木素-伊紅(HE)檢測各組小鼠胃病理改變;TEM觀察各組小鼠胃中TCs的形態(tài)變化;mFIHC檢測各組小鼠胃組織中TCs的數(shù)量。結(jié)果 小鼠胃正常組織中,黏膜層TCs數(shù)量較少,黏膜下層和肌層中TCs相對較多,TCs的胞體呈長梭形或紡錘形,具有細長伴節(jié)狀膨大的端足(Tps),與血管、神經(jīng)和平滑肌伴行交聯(lián),形成網(wǎng)狀結(jié)構(gòu);免疫表型為CD34+/PDGFR-α+/CD31-/c-kit-,與人胃組織中的一致。與對照組比較,小鼠胃癌組織中,TCs的形態(tài)發(fā)生改變,網(wǎng)狀結(jié)構(gòu)缺失,分布密度顯著下降,數(shù)量顯著減少(P<0.01);與模型組相比,左金方組均能改善TCs的變化,高劑量組明顯減輕了胃組織的病理損傷,TCs的形態(tài)和網(wǎng)狀結(jié)構(gòu)逐漸恢復(fù),數(shù)量回升,差異有統(tǒng)計學(xué)意義(P<0.01)。結(jié)論 TCs在小鼠胃組織各層均有分布,其免疫表型為CD34+/PDGFR-α+/CD31-/c-kit-,逆轉(zhuǎn)TCs的缺失可能是左金方抗胃癌作用的重要機制。
[Key word]
[Abstract]
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 highdose 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
[中圖分類號]
R285.5
[基金項目]
深圳市基礎(chǔ)研究面上項目(JCYJ20220531102208019);深圳市藥學(xué)會醫(yī)院藥學(xué)研究基金(恒瑞基金)(SZ2022A25);深圳市醫(yī)療衛(wèi)生三名工程項目(SZZYSM202111002);深圳大學(xué)2024年度聚徒項目(聚徒+學(xué)術(shù))