摘要
目的:阐明大鼠脑缺血再灌注(I/R)后miR-137对转铁蛋白受体(TFR)和胸腺癌抵抗蛋白(BCRP)表达的调控作用及温阳复元方的干预效应。方法:75只SD大鼠分为五组,假手术组和模型组予0.9%氯化钠溶液灌胃,余组予温阳复元方灌胃,miR-137模拟组和miR-137模拟对照组大鼠使用脑立体定位法分别将miR-137模拟剂和miR-137空载体注射到缺血侧MCA区,成模后再灌注24 h、7 d、14 d大鼠取材;评价各组大鼠的神经功能缺损评分以及TTC染色;分别通过RT-qPCR、Western blot检测各组大鼠脑组织中相关蛋白和mRNA的表达情况。结果:与假手术组相比,模型组大鼠神经功能缺陷评分较高(P<0.01);成模后大鼠脑组织出现明显的白色梗死灶。与模型组比较,温阳复元方组、miR-137模拟组和miR-137模拟对照组大鼠脑组织中miR-137以及TFR mRNA和蛋白表达量均明显降低,其中miR-137模拟组降低最为显著(P<0.01);同时,大鼠脑组织中BCRP mRNA和蛋白表达均明显升高,其中miR-137模拟组升高最为明显(P<0.01)。结论:miR-137可能通过下调TFR、上调BCRP的表达,从而达到对大鼠神经元的保护作用,温阳复元方能进一步增强其保护作用。
Objective:To elucidate the regulatory effects of miR-137 on the expression of transferrin receptor(TFR)and thymic carcinoma resistance protein(BCRP)after cerebral ischemia/reperfusion(I/R)in rats and the intervention effect of Wenyang Fuyuan formula.Methods:Seventy-five SD rats were divided into five groups:the sham-operated group and the model group were given 0.9%NaCl solution by gavage,and the remaining group was given Wenyang Fuyuan formula by gavage.miR-137 mimic and miR-137 mimic control rats were injected with miR-137 mimic and miR-137 empty vector into the ischemic side of the MCA area using the brain stereotaxic method,and then perfused for 24 h,7 d,and 14 d after model formation.The rats were sacrificed at 14 d for sampling;the neurological deficit scores and TTC staining of each group were evaluated;the expression of relevant proteins and mRNAs in the brain tissue of each group were detected by RT-qPCR and Western blot,respectively.Results:Compared with the sham-operated group,the neurological function deficit score was higher in the model group rats(P<0.01);the brain tissues of rats showed obvious white infarct foci after modeling.Compared with the model group,the expression of miR-137 and TFR mRNA and protein in the brain tissue of rats in the Wenyang Fuyuan formula group,miR-137 mimic group and miR-137 mimic control group were significantly reduced,with the most significant reduction in the miR-137 mimic group(P<0.01);meanwhile,the expression of BCRP mRNA and protein in the brain tissue of rats were significantly increased,with the most significant increase in the miR-137 mimic group.The expression of BCRP mRNA and protein in rat brain tissues was significantly increased,with the most significant increase in the miR-137 mimic group(P<0.01).Conclusion:miR-137 may play a neuronal protective role by down-regulating TFR and up-regulating the expression of BCRP,and its protective effect can be further enhanced by Wenyang Fuyuan formula.
作者
李丽琴
张鼎
袁莉
向军军
陈炜
胡跃强
LI Liqin;ZHANG Ding;YUAN Li;XIANG Junjun;CHEN Wei;HU Yueqiang(Guangxi University of Chinese Medicine,Nanning 530001,China)
出处
《陕西中医》
CAS
2023年第10期1354-1359,共6页
Shaanxi Journal of Traditional Chinese Medicine
基金
国家自然科学基金资助项目(81973768)
广西自然科学基金资助重点项目(2019GXNSFDA245006)
广西中医脑病临床研究中心项目(桂科AD20238028)。
作者简介
通讯作者:胡跃强,E-mail:137463195@qq.com。
