中华放射医学与防护杂志

吴琼,袁蕾,余敏,刘政海,王贞,杨惠,李彩,艾小红,何洁,万炜.间歇性热量限制对辐射所致认知障碍的保护作用[J].中华放射医学与防护杂志,2022,42(5):335-342

间歇性热量限制对辐射所致认知障碍的保护作用

Effect of intermittent fasting on the cognitive dysfunction induced by irradiation

投稿时间：2021-12-14

DOI：10.3760/cma.j.cn112271-20211214-00483

英文关键词:Irradiation Intermittent fasting Cognitive dysfunction Autophgy Recombinant Voltage Dependent Anion Channel Protein 1 (VDAC1)

基金项目:湖南省自然科学基金(2021JJ30052,2020JJ4543,2019JJ40257);海南省海南医学院研究生创新课题研究项目(HYYS2020-31)

作者	单位	E-mail
吴琼	海南省热带脑科学研究与转化重点实验室, 海口 571199
袁蕾	海南省热带脑科学研究与转化重点实验室, 海口 571199
余敏	湖南省郴州市第一人民医院药剂科, 郴州 423001
刘政海	南华大学衡阳医学院应用解剖与生殖医学研究所, 衡阳 421001
王贞	湖南环境生物职业技术学院医学院, 衡阳 421001
杨惠	江西省赣州市人民医院病理科, 赣州 341099
李彩	南华大学衡阳医学院应用解剖与生殖医学研究所, 衡阳 421001
艾小红	南华大学附属第一医院肿瘤放疗科, 衡阳 421001
何洁	海南医学院病理学教研室, 海口 571199
万炜	海南省热带脑科学研究与转化重点实验室, 海口 571199	david-wan@163.com

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中文摘要:

目的探讨间歇性热量限制对辐射所致小鼠认知功能障碍的作用及可能机制。方法将36只7周龄c57BL/6J雄性小鼠按随机数表法分为假辐射+随意饮食组(sham-irradiation and ad libitum,Sham-AL)、辐射+随意饮食组(irradiation and ad libitum,IR-AL)、辐射+间歇性热量限制组(irradiation and intermittent fasting,IR-IF),每组12只。采用新旧事物识别实验检测各组小鼠认知功能;Western blot分别检测小鼠海马自噬相关基因5(ATG5)、微管相关蛋白1轻链3-II(LC3II)、自噬接头蛋白P62、线粒体阴离子通道蛋白1(VDAC1)、白介素1(IL-1β)、突触囊泡膜蛋白(SYP)、突触蛋白1(SYN-1)、突触后致密物-95(PSD95);免疫荧光法确定VDAC1在小鼠海马中定位。结果与Sham-AL组新事物识别指数(30.02 ±9.05)相比,IR-AL组小鼠新事物识别指数(-22.45 ±16.76)下降,两组比较差异有统计学意义(t=3.03,P<0.05)。与Sham-AL组相比,IR-AL组自噬标记蛋白ATG5和LC3II表达下降,抗自噬蛋白P62表达升高,VDAC1蛋白表达下降,IL-1β蛋白表达上升,SYP、SYN-1、PSD95蛋白表达降低(t=2.49、2.19、2.40、3.47、2.87、2.25、2.17、2.31,P<0.05)。与IR-AL组新事物识别指数(-22.45 ±16.76)相比,IR-IF组小鼠新事物识别指数(21.22 ±5.62)上升,两组比较差异有统计学意义(t=2.70,P<0.05)。与IR-AL组相比,IR-IF组自噬标记蛋白ATG5和LC3II表达上升,抗自噬蛋白P62表达降低,VDAC1蛋白表达升高,IL-1β蛋白表达下降,SYP、SYN-1、PSD95蛋白表达升高(t=2.88、2.71、3.18、3.18、3.11、3.30、3.35、2.53,P<0.05)。免疫荧光显示,VDAC1与离子钙接头蛋白分子1(IBA-1,小胶质细胞标记物)和神经胶质纤维酸性蛋白(GFAP,星形胶质细胞标记物)共表达,但与神经元核抗原蛋白(NEUN,神经元标记物)不共表达。结论间歇性热量限制可改善小鼠放射性认知功能障碍,其机制可能与上调海马区VDAC1蛋白表达、诱导自噬发生,最终抑制炎症因子释放和保护神经元突触可塑性有关。

英文摘要:

Objective To investigate the protective effect of intermittent fasting on radiation-induced cognitive impairment and the possible underlying mechanism.Methods A total of 36 male 7-week old c57BL/6J mice were divided into Sham-irradiation and ad libitum (Sham-AL) group, irradiation and ad libitum (IR-AL) group, and irradiation add intermittent fasting (IR-IF) group according to the random number table method, with 12 mice in each group. The cognitive function of mice was assessed by novel object recognition task. The expressions of autophagy gene 5 (ATG5), microtubulesas sociated protein light chain II (LC3II), voltage dependent anion channel protein 1 (VDAC1), interleukin-1β (IL-1β), synaptophysin (SYP), synapsin I (SYN-1), and postsynaptic density 95 (PSD95) were tested by Western blot. The location of VDAC1 in mice hippocampus was detected by immunofluorescence.Results The discrimination index (-22.45 ±16.76) of IR-AL group was significantly (t=3.032,P<0.05) lower than that of Sham-AL group (30.02 ±9.05). Compared to Sham-AL group, IR-AL group had a decreased expressions of autophagy-related proteins (ATG5 and LC3II), mitochondrial marker (VDAC1), inflammatory factors (IL-1β) as well as synapse-associated proteins SYP, SYN-1 and PSD95 (t=2.49, 2.19, 2.40, 3.47, 2.87, 2.25, 2.17, 2.31,P<0.05). Compared to IR-AL group, IR-IF group had an increased discrimination index (21.22 ±5.62) and the increased expressions of ATG5, LC3II, VDAC1, IL-1β, SYP, SYN-1, and PSD95 (t=2.70, 2.88, 2.71, 3.18, 3.18, 3.11, 3.30, 3.35, 2.53,P<0.05). The immunofluorescence assay revealed that VDAC1 was co-expressed with the markers of astrocytes (GFAP) and microglia (IBA-1), but not with neurons (NEUN).Conclusions Intermittent fasting could greatly improve the cognitive function of irradiated mice possibly by upregulating VDAC1 expression, induce autophagy, and inhibit the release of inflammatory factors and protecting the synapticplasticity in the hippocampus.

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