TIPE2和炎性细胞因子在鼠动脉硬化斑块形成中的表达及其相互关系

山东大学学报(医学版) ›› 2008, Vol. 46 ›› Issue (12): 1124-.

TIPE2和炎性细胞因子在鼠动脉硬化斑块形成中的表达及其相互关系

王永祥马盪高琦朱法良张利宁

山东大学医学院免疫学研究所，济南 250012

收稿日期:2008-07-04 出版日期:2008-12-16 发布日期:2009-12-16
通讯作者: 张利宁（1960- ），女，教授，主要从事免疫调节研究。
作者简介:王永祥（1983- ），男，硕士研究生，主要从事动脉粥样硬化免疫调节研究。
基金资助:
国家973科研基金资助课题（2006CB503803）。

Expression pattern and relationship of TIPE2 and inflammatoryfactors in atherosclerosis of ApoEknockout mice

WANG Yong-Xiang, MA Tian , GAO Qi, SHU Fa-Liang, ZHANG Li-Ning

Institute of Immunology, School of Medicine, Shandong University, Jinan 250012, China

Received:2008-07-04 Online:2008-12-16 Published:2009-12-16

摘要/Abstract

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。

关键词: 基因，TIPE2；炎性趋化因子类；动脉硬化；小鼠，基因敲除

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. ResultsWhen 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 IL-12p40, 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.

Key words: Gene, TIPE2; Chemokines; Aterosclerosis; Mice, Knockout

中图分类号:

R392.32

王永祥马盪高琦朱法良张利宁. TIPE2和炎性细胞因子在鼠动脉硬化斑块形成中的表达及其相互关系[J]. 山东大学学报(医学版), 2008, 46(12): 1124-.

WANG Yong-Xiang, MA Tian , GAO Qi, SHU Fa-Liang, ZHANG Li-Ning. Expression pattern and relationship of TIPE2 and inflammatoryfactors in atherosclerosis of ApoEknockout mice[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(12): 1124-.

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