富氢水缓解5-FU诱导的大鼠口腔粘膜溃疡

betway必威登陆网址（betway.com ）学报››2021,Vol. 42››Issue (9): 662-666.DOI:10.3969/j.issn.2097-0005.2021.09.005

富氢水缓解5-FU诱导的大鼠口腔粘膜溃疡

张单雅¹, 薛俊莉², 刘伯言², 陶鸽如²(), 石运芝¹(), 秦树存²()

^1.betway必威登陆网址（betway.com ），口腔医学院，山东泰安 271000
^2.betway必威登陆网址（betway.com ），生命betway必威亚洲中心，山东泰安 271000

收稿日期:2021-03-18出版日期:2021-09-25发布日期:2021-10-13
通讯作者:陶鸽如,石运芝,秦树存
作者简介:张单雅，口腔医学本科在读。
基金资助:
山东省大学生创新创业训练计划(20191828)

Alleviation effects of drinking hydrogen-rich water on the oral mucosal ulcer induced by 5-fluorouracil in rats

Danya Zhang¹, Junli Xue², Boyan Liu², Geru Tao²(), Yunzhi Shi¹(), Shucun Qin²()

^1.School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences，Taian 271000，China
^2.Life Sciences Research Center, Shandong First Medical University & Shandong Academy of Medical Sciences，Taian 271000，China

Received:2021-03-18Online:2021-09-25Published:2021-10-13
Contact:Geru Tao,Yunzhi Shi,Shucun Qin

摘要/Abstract

摘要： 目的

评估饮用富氢水对化疗药物5-氟尿嘧啶（5-FU）诱导口腔粘膜溃疡的缓解效果和可能的生物学作用。

方法

雄性SD大鼠连续2日腹腔注射5-FU（0.05 mg/g），第3日应用NaOH颗粒或20%乙酸接触颊部粘膜建立口腔溃疡模型，第5日给予实验大鼠饮用富氢水，于第10日处死动物取材。统计实验组大鼠存活率，观察口腔粘膜损伤情况，并使用Image J软件测量溃疡面积，ELISA法检测大鼠血清中TNF-α、IL-6、IL-1β的水平，免疫组织化学法检测颊粘膜中TNF-α、IL-6和iNOS的表达。

结果

饮用富氢水可提高实验组大鼠存活率；NaOH颗粒制造的溃疡，损伤面积大于注射20%乙酸造成的溃疡损伤，但饮用富氢水对溃疡损伤面积的影响差异无统计学意义（P> 0.05）。模型组大鼠血清中TNF-α、IL-6、IL-1β的含量均高于对照组，富氢水组较模型组有下降趋势但仅20%乙酸模型组IL-1β与对照组比较差异有统计学意义，余差异均无统计学意义。颊粘膜中TNF-α和IL-6在健康对照组中的表达较弱，在模型组中的阳性着色见于颊粘膜上皮细胞和炎性间质中；富氢水组的阳性着色较模型组减弱；iNOS在实验组颊粘膜中的阳性表达较少。

结论

氢分子可能通过抑制氧化应激相关炎症反应，减轻5-FU诱导的大鼠口腔粘膜溃疡。

关键词:富氢水,5-FU,口腔粘膜溃疡,大鼠

Abstract: Objective

To investigate the alleviation effects of drinking hydrogen-rich water on the oral mucosal ulcer induced by 5-fluorouracil （5-FU） and its possible biological mechanism.

Methods

Male SD rats were intraperitoneally injected with 5-FU （0.05 mg/g） for 2 consecutive days. On D3， rats were treated with NaOH particles or 20% acetic acid on buccal mucosa to establish oral ulcer model. From D5， the rats were given hydrogen-rich water， and the animals were sacrificed on the D10. The survival rates of rats in all experimental groups were counted， and the lesions of oral mucosa were measured by Image J software. The levels of TNF-α， IL-6 and IL-1β in serum were detected by ELISA， and the expressions of TNF-α， IL-6 and iNOS at buccal mucosa were detected by immunohistochemistry.

Results

Drinking hydrogen-rich water improved the survival rate of rats in the experimental groups. The damage area of ulcers produced by NaOH particles were larger than that caused by injection with 20% acetic acid （P< 0.05）， but there was no significant difference in the damage area of ulcers with drinking hydrogen-rich water or not （P> 0.05）. The serum levels of TNF-α， IL-6 and IL-1β of rats in model groups were significantly higher than those in the control group， while levels of the hydrogen-rich water group showed a downward trend compared with the model group. The expression of TNF-α and IL-6 at buccal mucosa were low in the healthy control and high in the model groups， while the expression in hydrogen-rich water groups showed a downward trend compared with the model group. The expression of iNOS at buccal mucosa was low in all groups.

Conclusion

Molecular hydrogen alleviates oral mucosal ulcers induced by 5-FU in rats possibly through inhibiting oxidative stress-related inflammation.

Key words:hydrogen-rich water,5-FU,oral mucosal ulcer,rat

中图分类号:

R780

张单雅, 薛俊莉, 刘伯言, 陶鸽如, 石运芝, 秦树存. 富氢水缓解5-FU诱导的大鼠口腔粘膜溃疡[J]. betway必威登陆网址（betway.com ）学报, 2021, 42(9): 662-666.

Danya Zhang, Junli Xue, Boyan Liu, Geru Tao, Yunzhi Shi, Shucun Qin. Alleviation effects of drinking hydrogen-rich water on the oral mucosal ulcer induced by 5-fluorouracil in rats[J]. Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences, 2021, 42(9): 662-666.

图/表5

图1大鼠口腔溃疡模型，20%乙酸模型组，颊粘膜表面覆盖一层可撕脱白膜（A），撕下可见粘膜红肿破溃（B）

图2大鼠口腔颊粘膜病理学观察A， B为健康对照组；C为A-N组；D为A-H组；E为B-N组；F为B-H组。标尺为50 μm。

图3富氢水抑制大鼠口腔溃疡动物实验，饮用富氢水可提高实验组大鼠存活率（A），而溃疡组织假膜面积无明显差异（B）

表1各组大鼠血清中炎性细胞因子水平（pg/mL）

细胞因子	Control	A-N	A-H	B-N	B-H
TNF-α	102.68 ± 45.97	162.59 ± 53.84	115.30 ± 82.86	169.87 ± 77.55	97.83 ± 49.63
IL-6	66.57 ± 39.40	112.78 ± 60.93	67.41 ± 49.37	130.12 ± 35.00	64.17 ± 37.81
IL-1β	21.20 ± 7.94	55.89 ± 26.54	40.48 ± 6.37	63.32 ± 20.95 ^a	45.57 ± 16.14

表1各组大鼠血清中炎性细胞因子水平（pg/mL）

细胞因子	Control	A-N	A-H	B-N	B-H
TNF-α	102.68 ± 45.97	162.59 ± 53.84	115.30 ± 82.86	169.87 ± 77.55	97.83 ± 49.63
IL-6	66.57 ± 39.40	112.78 ± 60.93	67.41 ± 49.37	130.12 ± 35.00	64.17 ± 37.81
IL-1β	21.20 ± 7.94	55.89 ± 26.54	40.48 ± 6.37	63.32 ± 20.95 ^a	45.57 ± 16.14

图4大鼠颊粘膜免疫组织化学染色Control为健康对照组；B-N为乙酸模型组；B-H为乙酸富氢水组。标尺为50 μm。

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