血管紧张素Ⅱ对大鼠骨髓间充质干细胞棕色脂肪变的抑制作用  

Inhibitory effect of angiotensin II on the brown fat differentiation of rat bone marrow mesenchymal stem cells

作　　者：刘晨洋 王瑾[1] 张文婷 王丽清 尹晓晓 赵俊楠 焦向英[1] Liu Chenyang;Wang Jin;Zhang Wenting;Wang Liqing;Yin Xiaoxiao;Zhao Junnan;Jiao Xiangying(Department of Physiology,School of Basic Medicine,Shanxi Medical University,Taiyuan 030001,Shanxi Province,China)

机构地区：[1]山西医科大学基础医学院生理学系,山西省太原市030001

出　　处：《中国组织工程研究》2025年第23期4859-4867,共9页Chinese Journal of Tissue Engineering Research

摘　　要：背景:骨髓间充质干细胞是脂肪细胞的来源之一,且表达所有肾素血管紧张素系统成分,但血清血管紧张素Ⅱ对骨髓间充质干细胞向棕色脂肪组织分化的影响尚不清楚。目的:观察血管紧张素Ⅱ对骨髓间充质干细胞向棕色脂肪细胞分化的影响,并探究血管紧张素1a型受体敲除对血管紧张素Ⅱ影响骨髓间充质干细胞向棕色脂肪细胞分化的作用及可能机制。方法:分离培养野生型SD大鼠及血管紧张素1a型受体敲除SD大鼠的骨髓间充质干细胞,将其培养至第3代,随机分为4组:野生组,基因敲除组,野生+血管紧张素Ⅱ组,基因敲除+血管紧张素Ⅱ组,在棕色脂肪诱导分化培养基中诱导分化14 d,后2组在每次更换分化培养基的同时加入100 nmol/L血管紧张素Ⅱ进行干预。采用Western blot、qRT-PCR、免疫荧光等方法检测棕色脂肪诱导分化、脂肪分解、β氧化和线粒体生物发生等相关标记物的表达。结果与结论:血管紧张素Ⅱ可抑制骨髓间充质干细胞向棕色脂肪细胞分化,敲除血管紧张素1a型受体基因能够通过促进脂肪分解、增强脂肪酸β氧化、促进线粒体生物发生、增强线粒体功能来改善血管紧张素Ⅱ对骨髓间充质干细胞向棕色脂肪细胞分化的抑制作用。这些发现为肥胖治疗提供了新的研究方向和潜在治疗靶点,揭示了肾素血管紧张素系统在脂肪代谢中的重要作用及其作为治疗目标的潜力。BACKGROUND:Bone marrow mesenchymal stem cells are one of the sources of adipocytes and express all renin-angiotensin system components,but the effect of angiotensin II on bone marrow mesenchymal stem cell differentiation into brown adipose tissue is not clear.OBJECTIVE:To observe the effect of angiotensin II on bone marrow mesenchymal stem cell differentiation into brown adipose tissue and investigate the role of angiotensin 1a receptor knockout in effect of angiotensin II on bone marrow mesenchymal stem cell differentiation into brown adipocytes and its potential mechanisms.METHODS:After isolation and culture of bone marrow mesenchymal stem cells in wild-type and angiotensin 1a receptor knockout SD rats,the cells were cultured to the third generation and randomly divided into four groups:wild type group,knockout group,wild type+angiotensin II group,and knockout+angiotensin II group.The differentiation was induced in the brown fat induced differentiation medium for 14 days.Angiotensin II(100 nmol/L)was added for intervention when the differentiation medium was changed each time in the latter two groups.Western blot assay,qRT-PCR,immunofluorescence,and other methods were used to detect the expression of induced differentiation,lipolysis,βoxidation,and mitochondrial biogenesis in brown fat.RESULTS AND CONCLUSION:Angiotensin II could inhibit the browning of rat bone marrow mesenchymal stem cells.Knockout of angiotensin 1a receptor could improve the inhibitory effect of angiotensin II on brown lipid formation of rat bone marrow mesenchymal stem cells by promoting lipolysis,enhancing fatty acidβoxidation,promoting mitochondrial biogenesis,and enhancing mitochondrial function.These findings provide new research directions and potential therapeutic targets for obesity treatment,revealing the important role of renin angiotensin systems in fat metabolism and its potential as a therapeutic target.

关 键 词：血管紧张素Ⅱ 骨髓间充质干细胞 棕色脂肪变 线粒体 β氧化 血管紧张素Ⅱ1a受体 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R335