PPAR-γ激动剂对ApoE基因敲除小鼠动脉粥样斑块及趋化因子CCL21及其受体CCR7的影响
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摘要
目的观察PPAR-γ激动剂(罗格列酮)对高脂饮食载脂蛋白E基因敲除(ApoE KO)小鼠动脉粥样斑块、趋化因子CCL21及其受体CCR7的表达的影响。
方法将40只载脂蛋白E基因敲除(ApoE KO)小鼠随机分为五组:普通饮食组、高脂饮食组、高脂饮食+罗格列酮低剂量组(5 mg·kg- 1·d- 1),高脂饮食+罗格列酮中等剂量组(10 mg·kg- 1·d- 1),高脂饮食+罗格列酮高剂量组(20 mg·kg- 1·d- 1)每组8只,分别予蒸馏水、蒸馏水、罗格列酮(低、中、高剂量)灌胃。12周后处死动物,心腔针刺取血检测血脂水平;ELISA法检测血中趋化因子CCL21水平;实时定量PCR法检测CCR7的表达水平,取主动脉斑标本HE染色,运用Densitograph Imaging Software软件进行分析主动脉斑块面积。
结果与正常饮食相比,高脂饮食组CCL21水平、斑块面积和血脂水平明显升高,罗格列酮能抑制高脂饮食组中CCL21水平。CCR7水平在普通饮食组最高,在高脂饮食中最低,在高脂饮食+(低、中、高剂量)罗格列酮组中罗格列酮能增强CCR7表达水平。
结论PPAR-γ激动剂(罗格列酮)有抗动脉粥样硬化作用,可能与趋化因子CCL21及其特异性受体CCR7表达水平有关。
Objective: To investigate the potential effects of PPARγagonist Rosiglitazone on the atherosclerosis lesion and chemokine ligand CCL21 and chemokine receptor CCR7 in high cholesterol-diet (HCD) apolipoprotein E knock-out (ApoE K O) mice.
Methods: 40 ApoE KO mice were randomly divided into 5 groups, given normal diet(ND) or HCD and randomized to no treatment or rosiglitazone 5mg.kg-1.d-1 or rosiglitazone 10mg.kg-1.d-1 or rosiglitazone 20mg.kg-1.d-1 for 12weeks groop. The plasma levels of chemokine ligand CCL21 were measured with ELISA method, and its chemokine recptor CCR7 were measured by real-time reverse transcription Fluourescent Quantitative polymerase chain reaction (RT- PCR ), The plasma total cholesterol and triglyceride and low density lipoprotein and high-sensitivity C-reactive protein (hs-CRP) concentration were measured by autoanalyzer, Atherosclerotic lesion area in aortic root was evaluated by HE staining with Densitograph Imaging Software.
Results :The ApoE KO mice with HCD was associated with a marked increase in plasma lipid levels ,hs-CRP,atherosclerotic lesion area, as well as the expressions of chemokine ligand CCL21. These changes were suppressed in mice treated with Rosiglitazone for 12 weeks concomitant with HCD administration .But the changes of CCR7 were significantly promoted in mice treated with Rosiglitazone .
Conclusion: Rosiglitazone could attenuate atherosclerosis, and this effect was in part related to inhibition expressions of chemokine ligand CCL21and to promote expressions of chemokine recptor CCR7.
方法将40只载脂蛋白E基因敲除(ApoE KO)小鼠随机分为五组:普通饮食组、高脂饮食组、高脂饮食+罗格列酮低剂量组(5 mg·kg- 1·d- 1),高脂饮食+罗格列酮中等剂量组(10 mg·kg- 1·d- 1),高脂饮食+罗格列酮高剂量组(20 mg·kg- 1·d- 1)每组8只,分别予蒸馏水、蒸馏水、罗格列酮(低、中、高剂量)灌胃。12周后处死动物,心腔针刺取血检测血脂水平;ELISA法检测血中趋化因子CCL21水平;实时定量PCR法检测CCR7的表达水平,取主动脉斑标本HE染色,运用Densitograph Imaging Software软件进行分析主动脉斑块面积。
结果与正常饮食相比,高脂饮食组CCL21水平、斑块面积和血脂水平明显升高,罗格列酮能抑制高脂饮食组中CCL21水平。CCR7水平在普通饮食组最高,在高脂饮食中最低,在高脂饮食+(低、中、高剂量)罗格列酮组中罗格列酮能增强CCR7表达水平。
结论PPAR-γ激动剂(罗格列酮)有抗动脉粥样硬化作用,可能与趋化因子CCL21及其特异性受体CCR7表达水平有关。
Objective: To investigate the potential effects of PPARγagonist Rosiglitazone on the atherosclerosis lesion and chemokine ligand CCL21 and chemokine receptor CCR7 in high cholesterol-diet (HCD) apolipoprotein E knock-out (ApoE K O) mice.
Methods: 40 ApoE KO mice were randomly divided into 5 groups, given normal diet(ND) or HCD and randomized to no treatment or rosiglitazone 5mg.kg-1.d-1 or rosiglitazone 10mg.kg-1.d-1 or rosiglitazone 20mg.kg-1.d-1 for 12weeks groop. The plasma levels of chemokine ligand CCL21 were measured with ELISA method, and its chemokine recptor CCR7 were measured by real-time reverse transcription Fluourescent Quantitative polymerase chain reaction (RT- PCR ), The plasma total cholesterol and triglyceride and low density lipoprotein and high-sensitivity C-reactive protein (hs-CRP) concentration were measured by autoanalyzer, Atherosclerotic lesion area in aortic root was evaluated by HE staining with Densitograph Imaging Software.
Results :The ApoE KO mice with HCD was associated with a marked increase in plasma lipid levels ,hs-CRP,atherosclerotic lesion area, as well as the expressions of chemokine ligand CCL21. These changes were suppressed in mice treated with Rosiglitazone for 12 weeks concomitant with HCD administration .But the changes of CCR7 were significantly promoted in mice treated with Rosiglitazone .
Conclusion: Rosiglitazone could attenuate atherosclerosis, and this effect was in part related to inhibition expressions of chemokine ligand CCL21and to promote expressions of chemokine recptor CCR7.
引文
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