脂连蛋白(adiponectin)对动脉粥样硬化小鼠的治疗作用及其机制

The therapeutic effect and its mechanism of adiponectin on ApoE^(-/-) mice with atherosclerosis

目的研究脂连蛋白(APN)对载脂蛋白E敲除(ApoE^(-/-))的动脉粥样硬化(AS)小鼠的治疗作用及可能机制。方法选取20只雄性ApoE^(-/-)小鼠通过高脂饮食建立AS模型,小鼠随机分为APN处理组及对照组。APN处理组给予腹腔注射重组小鼠APN(25μg/d),对照组给予腹腔注射等量生理盐水,共处理4周。采用HE染色和免疫组织化学染色、ELISA、免疫荧光标记技术、反转录PCR和Western blot分析其治疗作用和机制。结果与对照组相比,APN处理组动脉粥样硬化斑块面积、血管内白细胞介素8(IL-8)及肿瘤坏死因子α(TNF-α)水平均显著降低,血管周围脂肪组织炎症细胞浸润比例显著降低。APN处理组小鼠血管周围脂肪组织M1巨噬细胞标志物CD86及M1巨噬细胞下游促炎介质IL-1β表达均显著小于对照组,而M2巨噬细胞标志物CD206及M2巨噬细胞下游抗炎介质IL-10的水平均显著高于对照组。血管周围脂肪组织磷酸化的信号转导子与转录激活子6(p-STAT6)水平显著高于对照组。结论 APN对AS小鼠具有明确治疗效果,可能是通过激活STAT6信号诱导脂肪组织巨噬细胞M2巨噬细胞极化。

Objective To analyze the role of adiponectin（APN） in the treatment of ApoE^（-/-）mice with atherosclerosis（AS） and its possible mechanism. Methods Twenty male ApoE^（-/-）mice were enrolled to establish AS model with high-fat diet,and then randomly divided into control group（ saline, intraperitoneal injection,4 weeks） and APN-treated group（25 μg/d,intraperitoneal injection,4 weeks）. HE staining,immunohistochemistry,ELISA,immunofluorescence,reverse transcription PCR and Western blotting were performed to analyze the effect of APN on ApoE^（-/-）mice and the changes of related signaling pathways. Results Compared with the control group,the APN-treated group had smaller atheroma macular areas and lower levels of inflammatory cytokines（ IL-8 and TNF-α） in blood vessels. The APN-treated group had less inflammatory cell infiltration in perivascular adipose tissues than those of the control group. The APN-treated group had lower levels of CD86 and IL-1 β,but higher levels of CD206 and IL-10 in perivascular adipose tissues than those of the control group. Western blot analysis showed that APN treatment significantly increased the expression of p-STAT6 in perivascular adipose tissues as compared with that of the control group. Conclusion APN has a definitely therapeutic effect on ApoE^（-/-）mice,and the possible mechanism may be associated with the induced macrophage polarization through STST6 signal in perivascular adipose tissues.