Irbesartan对冠状动脉粥样硬化小鼠的治疗作用及可能机制

目的：明确Irbesartan对冠状动脉粥样硬化小鼠的治疗作用，并进一步分析可能的机制。方法：将16只雄性ApoE^-/- 小鼠给予高脂饮食（1.25%胆固醇，10%脂肪）构建冠心病模型。模型建立后将小鼠随机分为治疗组［Irbesartan,50 mg/(kg•d),4周］及对照组（等量生理盐水灌胃对照）。采用HE、ELISA、Western blot及免疫荧光技术分析疗效及机制。结果：治疗组小鼠动脉粥样斑块面积显著低于对照组（P＜0.05）。治疗组血管内IL-1β、IL-6及TNF-α水平显著低于对照组（P＜0.05）。治疗组小鼠血管周围脂肪组织内PPAR-γ及Adiponectin水平显著升高，而Leptin水平显著降低，与对照组相比差异具有统计学意义（P＜0.05）。Western blot及免疫荧光证实，Irbesartan显著抑制了治疗组小鼠血管周围脂肪组织内的NF-κB信号通路。结论：Irbesartan通过调节血管周围脂肪组织内PPAR-γ-NF-κb（p65）信号通路，调节血管周围脂肪组织功能及炎症，从而发挥抗动脉粥样硬化疗效。

Therapeutical effect of Irbesartan for coronary atherosclerosis mice (ApoE-/- )and its possible mechanisms

Objective:To analyze the therapeutical effect of Irbesartan for coronary atherosclerosis mice (ApoE^-/- ) and its possible mechanisms.Methods: A total of 16 male ApoE^-/- mice were randomly divided into control group and Treatment group ［Irbesartan,50 mg/(kg•d),4 weeks］.HE,immunofluorescence,Western blot and ELISA were performed to analyze the effect of Irbesartan on ApoE^-/- and the changes of related signaling pathways.Results: Compared with control group,the treatment group had lower atheroma macular areas and inflammatory cytokines in blood vessel (P＜0.05).Treatment group had lower levels of leptin,but higher levels of PPAR-γ and adiponectin in perivascular adipose tissues (PVAT) than these of control group,the difference were statistically significant (P＜0.05).Western blot and immunofluorescence analysis shown that Irbesartan treatment significantly depressed the expression of p-p65 and p-IKK in PVAT when compared with these of control group (P＜0.05).Conclusion: Irbesartan has significantly therapeutic effect on ApoE^-/- mice,the possible mechanisms including anti-inflammatory effects in PVAT,improved the adipose tissue function and regulated the PPAR-γ-NF-κB signaling pathways.