基于ACE-AngⅡ-AT1R/ACE2-Ang(1-7)-MAS轴探索miR-107调控无症状脑梗死小鼠脑血流的作用机制OA
Exploring the Mechanism of miR-107 in Regulating Cerebral Blood Flow in Asymptomatic Cerebral Infarction Mice Based on the ACE-AngⅡ-AT1R/ACE2-Ang(1-7)-MAS Axis
目的:基于miR-107对无症状脑梗死(SBI)小鼠ACE-AngⅡ-AT1R/ACE2-Ang(1-7)-Mas受体轴平衡的调控作用,探讨其改善脑血流的可能作用机制.方法:采用微球注射法成功制作SBI模型小鼠16只,按1:1:1:1分入假手术组、SBI组、SBI+模拟物组、SBI+溶剂组,SBI+模拟物组予miR-107模拟物经侧脑室注入SBI小鼠颅内,SBI+溶剂组予注射0.9%生理盐水作为对照.利用激光散斑血流成像技术检测SBI小鼠的大脑血流情况;通过RT-qPCR技术检测小鼠大脑皮层的miR-107表达;利用ELISA和免疫印迹技术检测小鼠大脑皮层的ACE-AngⅡ-AT1R/ACE2-Ang(1-7)-Mas受体轴靶标分子和血管舒缩因子ET-1、NO的表达水平.结果:与假手术组比较,SBI组miR-107表达量显著减少,大脑皮层血流显著减少,大脑皮层的ACE、AngⅡ、AT1R蛋白表达显著增加,ACE2、Ang(1-7)、Mas1蛋白表达显著减少,ET-1、NO表达显著增加(P<0.05);与SBI组比较,SBI+模拟物组的miR-107表达量明显增加,大脑皮层血流明显增加,大脑皮层的ACE、AngⅡ、AT1R蛋白表达显著减少,ACE2、Ang-(1-7)、Mas1蛋白表达显著增加,ET-1、NO表达显著减少(P<0.05);SBI组与SBI+溶剂组的miR-107表达量,大脑皮层血流,大脑皮层的ACE、AngⅡ、AT1R、ACE2、Ang-(1-7)、Mas1蛋白表达,ET-1、NO表达差异均无统计学意义(P>0.05).结论:miR-107具有改善SBI脑血流灌注的作用,其作用机制可能与调控ACE-AngⅡ-AT1R/ACE2-Ang-(1-7)-Mas受体轴平衡进而下调血管舒缩因子ET-1、NO的表达水平相关.
Objective:To investigate the regulatory effect of miR-107 on the ACE-AngⅡ-AT1R/ACE2-Ang(1-7)-Mas axis in mice with silent brain infarction(SBI),and to explore its underlying mechanism in regulating cerebral blood flow(CBF).Methods:A mouse model of SBI was established by microsphere embolization.The mice were randomly divided into four groups:sham operation group,SBI model group,SBI+miR-107 mimic group,and SBI+solvent group.The SBI+mimic group was administered with miR-107 mimic via intracerebroventricular injection,while the SBI+solvent group received an equal volume of 0.9%normal saline as control.Cerebral blood flow in SBI mice was evaluated by laser speckle contrast imaging.The expression level of miR-107 in the mouse cerebral cortex was detected by RT-qPCR.ELISA and Western blotting were used to measure the expression levels of key molecules in the ACE-AngⅡ-AT1R/ACE2-Ang(1-7)-Mas axis and endothelial factors endothelin-1(ET-1)and nitric oxide(NO)in the mouse cerebral cortex.Results:Compared with the sham operation group,the SBI model group showed significantly downregulated expression of miR-107 and decreased CBF,accompanied by upregulated protein expression of ACE,AngⅡ,and AT1R,and downregulated protein expression of ACE2,Ang(1-7),and Mas1 in the cerebral cortex(P<0.05).Meanwhile,the expression levels of ET-1 and NO were significantly elevated in the SBI model group(P<0.05).Compared with the SBI model group,the SBI+mimic group exhibited significantly upregulated expression of miR-107 and improved CBF,downregulated protein expression of ACE,AngⅡ,and AT1R,and upregulated protein expression of ACE2,Ang(1-7),and Mas1 in the cerebral cortex(P<0.05).Moreover,the expression levels of ET-1 and NO were significantly decreased in the SBI+mimic group(P<0.05).There were no statistically significant differences in miR-107 expression,CBF,or the protein expression of ACE,AngⅡ,AT1R,ACE2,Ang(1-7),Mas1,ET-1,and NO between the SBI model group and the SBI+solvent group(P>0.05).Conclusion:miR-107 can improve cerebral blood flow perfusion in SBI mice,and its mechanism may be related to the regulation of the ACE-AngⅡ-AT1R/ACE2-Ang(1-7)-Mas axis,thereby downregulating the expression levels of ET-1 and NO.
吴镇宗;郑彦;邹春燕;陈丽明;王梦雪;尹莲花
福建中医药大学附属第二人民医院,福建 福州 350003福建中医药大学附属第二人民医院,福建 福州 350003福建中医药大学附属第二人民医院,福建 福州 350003福建中医药大学附属第二人民医院,福建 福州 350003福建中医药大学,福建 福州 350122福建中医药大学附属第二人民医院,福建 福州 350003
医药卫生
无症状脑梗死miR-107ACE-AngⅡ-AT1R/ACE2-Ang(1-7)-Mas受体轴脑血流
silent brain infarctionmiR-107ACE-AngⅡ-AT1R/ACE2-Ang(1-7)-Mas axiscerebral blood flow
《中医康复》 2026 (4)
31-38,8
国家自然科学基金青年科学基金项目(82004441)福建省引导性科技计划项目(2024Y0016)
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