不同剂量达格列净对ApoE^(-/-)动脉粥样硬化小鼠炎症反应及血脂代谢的影响  

Effects of different doses of dapagliflozin on inflammatory response and lipid metabolism in ApoE^(-/-)knockout atherosclerotic mice

作　　者：李宵 赵季红 贾俊栋 王泰然[1] LI Xiao;ZHAO Jihong;JIA Jundong;WANG Tairan(Handan Central Hospital,Handan 056001,Hebei,China;Armed Police Characteristic Medical Center,Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury,Tianjin 300162,China)

机构地区：[1]邯郸市中心医院,河北邯郸056001 [2]武警特色医学中心·天津市心血管重塑与靶器官损伤重点实验室,天津300162

出　　处：《西部医学》2025年第3期350-355,共6页Medical Journal of West China

基　　金：邯郸市科学技术研究与发展计划项目(21422083111)。

摘　　要：目的探讨不同剂量的达格列净在ApoE^(-/-)小鼠动脉粥样硬化(AS)斑块进程中的影响。方法选取30只8周龄的雄性ApoE^(-/-)小鼠,经高脂饲料喂养8周后形成AS模型,依据随机数字表法将形成AS的ApoE^(-/-)小鼠,随机分为对照组(生理盐水)、低剂量达格列净组(达格列净0.5 mg/kg·d)和高剂量达格列净组(达格列净1 mg/kg·d),各组10只,干预4周后取材。主动脉及主动脉瓣冰冻切片行油红O染色,留取全血通过流式细胞术检测单核细胞亚群,主动脉瓣冰冻切片行经免疫荧光染色后通过共聚焦显微镜检测斑块内的增殖巨噬细胞的比例;血清经酶联免疫分析法检测总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C),白介素-1β(IL-1β),白介素-6(IL-6),肿瘤坏死因子-α(TNF-α)的水平。结果与对照组相比,不同剂量达格列净组主动脉及主动脉瓣区斑块负荷减轻(P<0.01),循环中Ly6 Chi单核细胞比例,主动脉瓣区增殖巨噬细胞比例,炎症因子IL-1β、IL-6、TNF-α,血脂中TC及LDL-C均显著降低(P<0.05),HDL-C明显升高(P<0.05)。与低剂量达格列净组相比,高剂量达格列净组斑块内增殖巨噬细胞比例,炎症因子IL-1β、IL-6、TNF-α,血脂中TC及LDL-C均显著降低(P<0.05)。结论达格列净在抑制AS发生发展作用的方面,低剂量与高剂量没有明显差异,这一作用可能与抑制炎症反应及调节脂质代谢相关,但高剂量达格列净在调制脂质代谢及抑制炎症反应方面效果更佳。Objective To investigate the effects of different doses of dapagliflozin on the progression of atherosclerotic plaque in ApoE-/-knockout mice.Methods We randomly assigned 30 ApoE-/-mice,which were fed high-fat diet for 8 weeks to establish AS model,into control group(placebo,n=10),Low-dose dapagliflozin group(0.5 mg/kg·d)and High-dose dapagliflozin group(1 mg/kg·d).Experimental sampling was started after 4 weeks of intervention.The aortic and frozen sections of aortic valve were stained with oil red O.The proportions of circulating monocyte subsets were analyzed by flow cytometry.The proportion of proliferating macrophages in the aortic valve plaque were detected by confocal microscopy after immunofluorescence staining.The serum levels of total cholesterol(TC),triglyceride(TG),high-density lipoprotein(HDLC),low-density lipoprotein(LDLC),interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)were detected by ELISA kit.Results Compared with the control group,the different doses of dapagliflozin groups had the effect of relieve the aortic and aortic valve plaque load,significantly reduced the proportion of Ly6 Chi monocytes in the circulation,alleviate the proportion of proliferating macrophages in the aortic valve,restrain the release of inflammatory cytokines IL-1β,IL-6 and TNF-α,reduced the levels of TC and LDLC,increased the levels of HDLC.Compared with the low-dose dapagliflozin group,the high-dose dapagliflozin group had significant reductions in the proportion of proliferating macrophages in the plaque,inflammatory factors IL-1β,IL-6,TNF-α,blood lipids TC and LDLC.Conclusion There is no significant difference between low dose and high dose of dapagliflozin in inhibiting the occurrence and development of AS.This effect may be related to inhibition the inflammatory response and regulation the lipid metabolism.Meanwhile,high-dose dapagliflozin has a better effect in regulating lipid metabolism and inhibiting inflammatory response.

关 键 词：达格列净 动脉粥样硬化 单核细胞亚群 增殖巨噬细胞 血脂 炎症因子 

分 类 号：R285.5[医药卫生—中药学] R543.5[医药卫生—中医学]