【摘要】 目的探讨新的免疫负调控分子TIPE2和炎性细胞因子在ApoE基因敲除鼠(ApoE-/-小鼠)动脉粥样硬化斑块形成中的表达及其相互关系,分析其在动脉粥样硬化中的作用。方法应用ApoE-/-小鼠构建动脉血管粥样硬化模型,普通C57野生型小鼠为对照组,通过对动脉血管HE染色及油红O染色判定斑块进展情况,并用RT-PCR的方法检测斑块局部TIPE2及白细胞介素-6(IL-6)、白细胞介素-12p40(IL-12p40)、转化生长因子-β(TGF-β)和肿瘤坏死因子-α(TNF-α)的表达,定量后分析其直线相关关系。结果8周龄ApoE-/-小鼠高脂喂养至16周后,动脉已形成明显粥样硬化斑块,同周龄野生型C57小鼠血管壁内未见斑块形成;TIPE2在ApoE-/-小鼠无斑块期(8周)、斑块早期(16周)及斑块中晚期(24周)主动脉中表达均明显高于C57对照组;IL-6在ApoE-/-小鼠主动脉斑块各时期表达与C57小鼠相比均无明显变化;而在无斑块期IL-12p40、TGF-β及TNF-α表达较C57小鼠已明显升高(P<0.05);在斑块早期时,TGF-β及TNF-α表达仍然高于对照组(P<0.05);但斑块进展到中晚期,仅有TGF-β较同周龄C57小鼠表达量高(P<0.05)。进一步分析发现,TIPE2的表达和TNF-α呈正相关,相关系数为0.757(P=0.007),但与IL-6、IL-12p40和TGF-β表达无明显相关性。结论TIPE2在ApoE-/-小鼠的表达较C57对照组明显升高,且与TNF-α正相关,提示TIPE2可能在动脉粥样硬化的发生中发挥作用。更多还原

【Abstract】 Objective To investigate the expression pattern of a new immune negative regulator,TIPE2(tumor necrosis factor-α induced protein 8 like 2)and the inflammatory factors of atherosclerosis plaque of ApoE-knockout mice(ApoE-/-mice) and to analyze the relationship between them.Methods ApoE-/-mice were used to establish atherosclerosis models and wild type C57 rats served as the controls.The formation of atherosclerosis plaque was observed under microscopy after HE and oil red O staining and then the expression of TIPE2 and inflammatory factors were determined by reverse-transcript polymerase chain reaction.After quantization,their linear correlation was analyzed.Results When the 8 week-old ApoE-/-mice were fed with high-fat until 16 or 24 weeks old, atherosclerosis plaque was found in the arteries,while this did not occur in the control group.Expression of TIPE2 at the aorta of ApoE-/-mice was significantly higher at no plaque stage(8 weeks),early stage(16 weeks) and middle-advanced stage(24 weeks) than that of the control group.Expression of IL-6 was not significantly different from that of the control group in all processes of atherosclerosis.When there was no plaque at the aorta,expression of IL12p40,TGF-β and TNF-α were significantly higher(P<0.05).During the early stage the expression of IL-12p40 decreased and there was no differencebetween the ApoE-/-and the C57 mice,while the expressions of TGF-β and TNF-α were significantly increased(P<0.05).With the development of plaque,expression of only TGF-β was increased(P<0.05) at the middle-advanced stage.Further analysis showed that expression of TIPE2 was positively correlated with that of TNF-α but was not relevant to expression of IL-6,IL-12p40 and TGF-β. Conclusion TIPE2 expression at the aorta of the ApoE-/-mice is significantly higher than that of the control group and is positively correlated with that of TNF-α,indicating the role of TIPE2 in the origin of atherosclerosis.更多还原