Previous studies have indicated that the JAK/STAT signaling pathway is involved in modulating arterial adventitia inflammation response. In this study, we designed experiments to further investigate the effect of JAK2/STAT3/SOCS3 signaling in rabbit atherosclerosis process. Atherosclerosis was induced in the abdominal arteries of rabbits by balloon injury of the aorta supplemented by the atherogenic diet. Simultaneously, in the process of atherosclerosis, animals underwent either ruxolitinib treatment or not for 12 weeks. At the end of the experimental period, all rabbits were sacrificed. The plaque areas in abdominal artery, the lipid burden of plaque and the calcium burden of plaque were detected by H&E staining, Oil Red O staining and Alizarin Red staining, respectively. In addition, rabbit plasma lipids and inflammatory cytokines were measured by biochemical test kits or ELISA kits. Finally, the expression and phosphorylation levels of JAK2/STAT3/SOCS3 pathway-related proteins were detected by RT-qPCR, western blot and immunohistochemistry assays. H&E staining and CT scan analysis showed that rabbit atherosclerosis model was constructed successfully. Ruxolitinib, an inhibitor of the Janus kinase 2 (JAK2), substantially reduced the area of atherosclerotic plaques in rabbits treated with high fat diet and balloon injury of the aorta. Moreover, ruxolitinib significantly decreased IL-6, IL-1β, IFN-γ and TNF-α, but increased IL-10 and IL-17 levels in plasma of atherosclerotic rabbits. Additionally, ruxolitinib reduced plasma TC, TG and LDL-C contents and AIP value, while enhanced HDL-C level in atherosclerotic rabbits. Furthermore, we found that JAK2 and STAT3 phosphorylation were up-regulated in rabbits with atherosclerosis when compared with those of the control group, followed by the expression of SOCS3 was also increased due to the activation of JAK2 and STAT3. Interestingly, ruxolitinib could inactivate JAK2 and STAT3 pathway and decrease SOCS3 expression. Taken together, the inhibition of JAK2/STAT3/SOCS3 signaling pathway may be a novel method for the clinical treatment of artery atherosclerosis.

中文翻译：

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抑制 JAK2/STAT3/SOCS3 信号减弱兔动脉粥样硬化

先前的研究表明 JAK/STAT 信号通路参与调节动脉外膜炎症反应。在本研究中，我们设计了实验来进一步研究 JAK2/STAT3/SOCS3 信号在兔动脉粥样硬化过程中的作用。动脉粥样硬化是由主动脉球囊损伤引起的，辅以致动脉粥样硬化的饮食，在兔子的腹动脉中诱发了动脉粥样硬化。同时，在动脉粥样硬化过程中，动物接受或不接受鲁索替尼治疗12周。实验结束时，处死所有兔子。腹动脉斑块面积、斑块脂质负荷和斑块钙负荷分别采用H&E染色、油红O染色和茜素红染色检测。此外，兔血脂和炎性细胞因子采用生化试剂盒或ELISA试剂盒测定。最后，通过 RT-qPCR、蛋白质印迹和免疫组织化学检测检测 JAK2/STAT3/SOCS3 通路相关蛋白的表达和磷酸化水平。H&E染色和CT扫描分析表明兔动脉粥样硬化模型构建成功。Ruxolitinib 是 Janus 激酶 2 (JAK2) 的抑制剂，可显着减少接受高脂肪饮食和主动脉球囊损伤治疗的兔子的动脉粥样硬化斑块面积。此外，鲁索替尼显着降低了动脉粥样硬化兔血浆中的 IL-6、IL-1β、IFN-γ 和 TNF-α，但增加了 IL-10 和 IL-17 水平。此外，鲁索替尼降低了动脉粥样硬化兔的血浆 TC、TG 和 LDL-C 含量和 AIP 值，同时提高了 HDL-C 水平。此外，我们发现与对照组相比，动脉粥样硬化兔的 JAK2 和 STAT3 磷酸化上调，随后由于 JAK2 和 STAT3 的激活，SOCS3 的表达也增加。有趣的是，ruxolitinib 可以灭活 JAK2 和 STAT3 通路并降低 SOCS3 表达。综上所述，抑制JAK2/STAT3/SOCS3信号通路可能是临床治疗动脉粥样硬化的一种新方法。