C-reactive protein/oxidised low-density lipoprotein/β2-glycoprotein I complex promotes atherosclerosis in diabetic BALB/c mice via p38mitogen-activated protein kinase signal pathway
C-reactive protein/oxidised low-density lipoprotein/β2-glycoprotein I complex promotes atherosclerosis in diabetic BALB/c mice via p38mitogen-activated protein kinase signal pathway
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DOI：
10.1186/1476-511x-12-42
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发表时间：
2013-03-26
影响因子：
4.5
通讯作者：
Yu, Pei
中科院分区：
文献类型：
--
作者：
Zhang, Rui;Zhou, Sai-Jun;Yu, Pei
背景资料：本研究旨在探讨C反应蛋白/氧化低密度脂蛋白/β 2糖蛋白I（CRP/oxLDL/β 2GPI）复合物对糖尿病BALB/c小鼠动脉粥样硬化（AS）的影响。8周后，高脂饲料喂养的小鼠注射链脲佐菌素（STZ）诱导糖尿病。糖尿病小鼠每月分别注射20 μ g oxLDL、20 μ g β 2GPI、40 μ g oxLDL/β 2GPI复合物、44 μ g CRP/oxLDL/β 2GPI复合物和PBS两次。主动脉用苏丹IV染色以研究脂质斑块形成。免疫组化法检测平滑肌细胞（SMC）、巨噬细胞和T细胞浸润情况。通过实时定量PCR定量与脂质代谢相关的受体的mRNA表达。Western blot检测主动脉组织中p38丝裂原活化蛋白激酶（p38 MAPK）和MKK 3/6的磷酸化水平。结果：oxLDL组和CRP/oxLDL/β 2 GPI组脂质斑块较oxLDL组广泛，管腔面积明显缩小，内膜与中膜厚度比值增加，正常内弹力拉米亚结构和内皮细胞消失（P <0.05）。CRP/oxLDL/β 2GPI复合物显著促进SMCs、巨噬细胞和T细胞浸润，增加ABCA 1和ABCG 1的mRNA表达，降低SR-BI和CD 3/6的mRNA表达，增加p38 MAPK和MKK 3/6的磷酸化（均P < 0.05）。结论：CRP/oxLDL/β 2GPI复合物通过增加脂质摄取加重糖尿病小鼠AS，其机制可能与p38 MAPK信号通路有关。
Background: The aim of this study was to investigate the effect of C-reactive protein/oxidised low-density lipoprotein/beta 2-glycoprotein I (CRP/oxLDL/beta 2GPI) complex on atherosclerosis (AS) in diabetic BALB/c mice.Methods: BALB/c mice were fed high-fat and normal diet. Eight weeks later, the mice fed with high-fat diet were injected with streptozotocin (STZ) to induce diabetes. The diabetic mice were respectively injected twice monthly with 20 mu g oxLDL, 20 mu g beta 2GPI, 40 mu g oxLDL/beta 2GPI complex, 44 mu g CRP/oxLDL/beta 2GPI complex, and PBS. Aortas were stained with Sudan IV to investigate lipid plaque formation. The infiltration condition of smooth muscle cells (SMCs), macrophages, and T cells in the aortas were determined by immunohistochemistry (IH). The mRNA expressions of receptors associated with lipid metabolism were quantified by real-time PCR. The phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) and MKK3/6 in aorta tissues were assessed by Western blot. The expression of inflammation cytokines was evaluated by protein chip.Results: The lipid plaques were more extensive, the lumen area was obviously narrower, the ratio of intima and media thickness were increased, and the normal internal elastic lamia structure and endothelial cell disappeared (P < 0.05) in the oxLDL and CRP/oxLDL/beta 2GPI groups (P < 0.05). CRP/oxLDL/beta 2GPI complex dramatically promoted infiltration of SMCs, macrophages, and T cells, improved the mRNA expression of ABCA1 and ABCG1, but reduced the mRNA expression of SR-BI and CD36 and increased the phosphorylation of p38MAPK and MKK3/6 (all P < 0.05). The highest expression levels of IL-1, IL-9, PF-4, bFGF, and IGF-II were detected in the CRP/oxLDL/beta 2GPI group (P < 0.05).Conclusions: CRP/oxLDL/beta 2GPI complex aggravated AS in diabetic BALB/c mice by increasing lipid uptake, the mechanism of which may be mediated by the p38MAPK signal pathway.