Molecular mechanism of cholesterol sensor SCAP dysfunction in atheroma formation in ApoE<sup>-/-</sup> mice induced by inflammation

周超; 季新忠; 刘巧; 伍莎莎; 欧阳南

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Molecular mechanism of cholesterol sensor SCAP dysfunction in atheroma formation in ApoE^-/- mice induced by inflammation

更新时间：2026-01-09

- Molecular mechanism of cholesterol sensor SCAP dysfunction in atheroma formation in ApoE^-/- mice induced by inflammation
- Journal of Army Medical University Vol. 38, Issue 9, Pages: 938-943(2016)
- 作者机构：
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  CLC： R341;R364.5;R543.502
- Published：2016
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周超,季新忠,刘巧,伍莎莎,欧阳南.炎症诱导SCAP功能失调促进ApoE-/-小鼠动脉粥样硬化的分子机制[J].陆军军医大学学报(原第三军医大学学报),2016,38(09):938-943.

　Zhou Chao,Ji Xinzhong,Liu Qiao,Wu Shasha,Ouyang Nan.Molecular mechanism of cholesterol sensor SCAP dysfunction in atheroma formation in ApoE-/- mice induced by inflammation[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(09):938-943.
周超,季新忠,刘巧,伍莎莎,欧阳南.炎症诱导SCAP功能失调促进ApoE-/-小鼠动脉粥样硬化的分子机制[J].陆军军医大学学报(原第三军医大学学报),2016,38(09):938-943. DOI：

　Zhou Chao,Ji Xinzhong,Liu Qiao,Wu Shasha,Ouyang Nan.Molecular mechanism of cholesterol sensor SCAP dysfunction in atheroma formation in ApoE-/- mice induced by inflammation[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(09):938-943. DOI：

摘要

目的探讨炎症诱导胆固醇调节元件结合蛋白裂解激活蛋白（sterol regulatory element binding proteins cleavage-activating protein，SCAP）功能失调促进ApoE

-/-

小鼠动脉粥样硬化形成的分子机制。方法 24只8周龄雄性ApoE

-/-

小鼠（C57BL/6遗传背景，体质量18～24 g）随机分组为高胆固醇饮食组（n=12，对照组）和高胆固醇饮食+炎症组（n=12，炎症组）。炎症组小鼠给予隔日皮下注射10%酪蛋白，非炎症组小鼠给予隔日皮下注射生理盐水，共14周。双抗夹心ELISA法检测ApoE

-/-

小鼠血清炎症指标（serum amyloid A，SAA）和TNF-α水平，HE染色观察ApoE

-/-

小鼠主动脉结构及局部炎症细胞浸润情况，油红O染色观察ApoE

-/-

小鼠主动脉斑块形成情况，Real-time PCR法与免疫组织化学法检测ApoE

-/-

小鼠主动脉LDLr、SREBP2、SCAP、α-甘露糖苷酶Ⅰ及α-甘露糖苷酶ⅡmRNA与蛋白表达。结果炎症组小鼠血清SAA[（529±23）ng/mL

]

与TNF-α[（37 900±3 100）ng/mL

]

水平显著高于对照组小鼠血清SAA[（248±27）ng/mL

]

与TNF-α[（1 789±219）ng/mL

]

水平（P0.01），表明ApoE

-/-

小鼠炎症模型建立成功。炎症组小鼠较对照组小鼠主动脉粥样硬化性病变更为严重(P0.01)，其LDLr、SCAP及α-甘露糖苷酶ⅡmRNA及蛋白表达、细胞核内NSREBP2水平明显高于对照组（P0.05）。结论炎症通过增加血管壁细胞内胆固醇敏感器SCAP的表达，并通过增强高尔基体α-甘露糖苷酶Ⅱ对SCAP的糖基化修饰，促进ApoE

-/-

小鼠动脉粥样硬化的发生和发展。

Abstract

Objective To investigate the mechanism of the dysfunction of sterol regulatory element binding proteins cleavage-activating protein (SCAP)

induced by inflammation in the promotion of atheroma formation in ApoE

-/-

mice. Methods A total of 24 male ApoE

-/-

mice (C57BL/6 background

8 weeks old

weighting 18 to 24 g) were randomly divided into 2 groups

that is

high-sterol feeding group (H) and feeding+inflammation group (HC). Beside high fat diet feeding

the mice in the inflammation group were injected with 10% casein subcutaneously every other day

while those of control group were subjected to normal saline. After 14 weeks’ treatment

the serum inflammatory markers

serum amyloid A (SAA) and TNF-α were determined by ELISA

the lipid accumulation in the aorta was observed by HE and Oil Red O staining

the expression of low-density lipoprotein receptor (LDLr)

SCAP

α-mannosidases Ⅰ and Ⅱ were examined using real-time PCR and immunohistochemical assay. Results The level of SAA and TNF-α were dramatically higher in the serum of ApoE

-/-

mice receiving subcutaneous injection of 10% casein (inflammation group) than control group (529±23 vs 248±27 ng/mL

37 900±3 100 vs 1 789±219 ng/mL

P0.01)

which indicated that the inflamed mice model was established successfully. The inflamed mice displayed more severe atheroma (P0.01)

and increased expression of LDLr

SCAP and α-mannosidaseⅡ at the mRNA (P0.05) and protein levels (P0.05) in the aorta

especially the active fragment NSREBP2 in the nucleus (P0.05) when compared with the mice in control group. Conclusion Inflammation enhances the expression of SCAP

and promotes SCAP glycosylation by up-regulating the expression of α-mannosidase Ⅱ in the aorta

and thus improves the atheroma formation in ApoE

-/-

mice.

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Molecular mechanism of cholesterol sensor SCAP dysfunction in atheroma formation in ApoE-/- mice induced by inflammation

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摘要

Abstract

关键词

Keywords

references

Molecular mechanism of cholesterol sensor SCAP dysfunction in atheroma formation in ApoE^-/- mice induced by inflammation