血清淀粉样P物质对ApoE-/-小鼠动脉粥样硬化的影响

Effects of serous amyloid P component on atherosclerosis in ApoE^(-/-) mice

目的研究血清淀粉样P物质(SAP)对血清对氧磷酶1(PON1)活性、炎症因子单核细胞趋化蛋白-1(MCP-1)及Apo E-/-小鼠动脉粥样硬化发生发展的影响,探讨SAP调节动脉粥样硬化的可能机制。方法 C57/BL6雄性小鼠6只为正常组,予普通饮食喂养;雄性Apo E-/-小鼠12只高脂饲料喂养12周,随机分为SAP组和PBS组,每组各6只,SAP组予腹腔注射SAP(6mg/g),隔天1次,共14d,PBS组予腹腔注射PBS(6mg/g),隔天1次,共14d。第16周时收集各组血液及动脉标本,检测小鼠血清血脂4项和PON1活性,ELISA检测血清SAP和MCP-1水平,HE染色观察动脉斑块大小,油红O染色观察斑块内脂质沉积情况,免疫组化检测斑块内SAP的表达。结果与正常组相比,PBS组和SAP组小鼠血清PON1活性明显下降(P<0.01),MCP-1水平明显增高(P<0.01),血管内大量斑块形成;与PBS组相比,SAP组小鼠血清PON1活性增高(P=0.046),MCP-1水平明显下降(P=0.032),血管内斑块面积减少(P=0.001),斑块内油红O阳性脂肪细胞数量减少(P=0.03)。结论 SAP可能通过提高PON1活性、降低MCP-1水平而延缓动脉粥样硬化的发生发展。

Objective To investigate the effect of serous amyloid P （SAP） component on serum paraoxonase 1 （PON1） activity, serum monocyte chemotactic protein 1 （MCP-1） expression and atherosclerosis progression in ApoE-/- mice, and explore the possible mechanisms thereof. Methods Six male C57/BL6 mice were fed with chow diet as normal control group. Twelve male ApoE-/- mice fed with western diet for 12 weeks were used to establish animal models of atherosclerosis, and then randomly divided into two groups （6 each）： SAP and PBS group. Mice in SAP group were treated （i.p.） with SAP （6mg/g） every other day from day 0 to day 14. Mice in normal and PBS group were treated （i.p.） with PBS （same volume as SAP group） every other day from day 0 to day 14. The blood specimen and aorta vascular tissues were collected at the 16th week after the first immunization. Serum lipids and PON1 activity were assessed. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression of serum SAP and MCP-1. Hematoxylin-eosin （HE） staining was used to observe the formation of atherosclerotic plaque. Oil red O staining was performed to observe the lipid accumulation, and immunohistochemical staining was performed to detect the SAP expression in the atherosclerotic plaque. Results Compared with the normal group, the serum PON1 activity reduced significantly while MCP-1 expression increased （P〈0.01）, and a large number of plaques formed in the blood vessels of mice in SAP and PBS group. Compered with PBS group, SAP treatment markedly improved the PON1 activity （P=0.046） and down-regulated MCP-1 expression （P=0.032）. Furthermore, SAP treatment significantly reduced atherosclerotic plaque area （P=0.001） and oil red O positive area （P=0.03）. Conclusion SAP could mitigate atherosclerotic lesion through improving the property of PON1 and down-regulating the level of MCP-1.