针刺研究2024，Vol.49Issue(7)：736-742,7.DOI:10.13702/j.1000-0607.20230782
艾灸调控SNX5对帕金森病模型小鼠神经元铁死亡的影响
Moxibustion improves motor function by down-regulating SNX5 and inhibiting ferroptosis in neurons of corpus striatum in mice with Parkinson's disease
摘要
Abstract
Objective To explore the effect of moxibustion on the expression of sorting nexin 5(SNX5),glutathione peroxidase(GPX4)and ferritin heavy chain(FTH1)in the corpus striatum in mice with Parkinson's disease(PD),so as to explore its mechanisms underlying improvement of PD by ameliorating ferroptosis in the substantia nigra striatum.Methods C57BL/6J mice were randomly divided into normal,sham operation,model,and moxibustion groups,with 10 mice in each group.The PD model was established by unilateral injection of 6-hydroxydopamine(3.5 μL)into the right medial forebrain bundle(AP=-1.2 mm,ML=-1.3 mm,DV=-4.75 mm).The mice in the moxibustion group received moxibustion at"Baihui"(GV20)and"Sishencong"(EX-HN1)for 20 min each time,once a day,6 times a week for 4 weeks.After the intervention,mice received apomorphine rotation behavior detection and pole climbing test.The expression of tyrosine hydroxylase(TH)in the substantia nigra was detected by immunofluorescence,the contents of Fe2+,malondialdehyde(MDA),the ratio of glutathione/oxidized glutathione(GSH/GSSG)in the corpus striatum were detected by using photocolorimetric method,and the expression levels of SNX5(endocytosomal protein),GPX4(one of the key targets for inhibiting ferroptosis)and FTH1 proteins and mRNAs in the corpus striatum were detected by Western blot and qPCR,respectively.Results Behavior tests showed that the pole climbing time and number of body rotation were significantly increased in the model group relevant to the sham operation group(P<0.01),and strikingly decreased in the moxibustion group relevant to the model group(P<0.01).The immunofluorescence intensity of TH in the substantia nigra,the ratio of GSH/GSSG,and the expression levels of GPX4 and FTH1 mRNAs and proteins in the corpus striatum were markedly decreased(P<0.01,P<0.05),while the contents of Fe2+and MDA and the expression levels of SNX5 mRNA and protein in the corpus striatum significantly increased in the model group relevant to the sham operation group(P<0.01,P<0.05).Compared with the model group,the decreased immunofluorescence intensity of TH,GSH/GSSH,and the expression levels of GPX4 and FTH1 mRNAs and proteins,and the increased contents of Fe2+and MDA and the expression levels of SNX5 mRNA and protein were reversed in the moxibustion group relevant to the model group(P<0.01,P<0.05).Conclusion Moxibustion may improve motor dysfunction in PD mice,which may be related to its effects in down-regulating the expression of SNX5,promoting the synthesis of GSH,decreasing the contents of Fe2+and MDA,up-regulating the ratio of GSH/GSSG and the expression of GPX4 and FTH1 mRNAs and proteins in the corpus striatum,and inhibiting the occurrence of ferroptosis.关键词
艾灸/帕金森病/铁死亡/分选连接蛋白5Key words
Moxibustion/Parkinson's disease/Ferroptosis/Sorting nexin 5引用本文复制引用
高达,黎庆连,王启章,吴春晓,郝小倩,汪晓铃,李萌竹,赵丽君,朱美玲..艾灸调控SNX5对帕金森病模型小鼠神经元铁死亡的影响[J].针刺研究,2024,49(7):736-742,7.基金项目
广东省自然科学基金项目(No.2022A151510450) （No.2022A151510450）
深圳市自然科学基金项目(No.JCYJ20220530150212028) （No.JCYJ20220530150212028）
深圳市"医疗卫生三名工程"项目(No.SZZYSM202106009) （No.SZZYSM202106009）
深圳市宝安中医药发展基金会项目(No.2022KJCX-ZJZL-7) （No.2022KJCX-ZJZL-7）
