摘要
目的:观察过氧化物酶体增殖活化受体γ(PPARγ)和酰基辅酶A:胆固醇酰基转移酶1(ACAT1)在肺炎衣原体(C.pn)诱导巨噬细胞泡沫化中的作用。方法:给予C.pn(1×105-1×106IFU)感染和/或PPARγ的配体罗格列酮(1-20μmol/L)孵育THP-1源性巨噬细胞48h。运用油红O染色观察细胞浆内脂滴的变化,酶荧光学法检测细胞内胆固醇酯含量的变化。分别运用RT-PCR和Western blotting检测ACAT1、PPARγ mRNA和蛋白表达。结果:高浓度的C.pn(5×105和1×106IFU)感染使THP-1源性巨噬细胞内脂滴明显增多,胆固醇酯与总胆固醇的比值明显增加(>50%)。C.pn感染呈浓度依赖性上调ACAT1 mRNA和蛋白表达,并且浓度依赖性地下调PPARγ mRNA和蛋白表达(P<0.05)。高浓度的罗格列酮(10、20μmol/L)明显抑制C.pn诱导的细胞内脂质滴的增多和胆固醇酯含量的增加,同时罗格列酮呈浓度依赖性抑制C.pn诱导的ACAT1 mRNA和蛋白表达的上调(P<0.05)。结论:C.pn经PPARγ途径上调ACAT1表达,进而诱导巨噬细胞泡沫化,这为进一步阐明C.pn感染促进动脉粥样硬化发生发展提供一个新的理论依据。
AIM： To investigate the expressions of peroxisome proliferator - activated receptor γ （PPAR γ） and acyl - coenzyme A： cholesterol acyltransferase - 1 （ ACAT1 ）, and to discuss the mechanisms and pathways of Chlamydia pneumoniae （ C. pn） - induced macrophage foam cell formation. METHODS： THP - 1 - derived macrophages were incubated for 48 h with or without C. pn （ 1 × 10^5 to 1× 10^6 IFU） and/or rosiglitazone （ 1 to 20 μmol/L）, a specific PPAR ~ agonist. Lipid droplets in cytoplasm were observed by oil red 0 staining. The contents of intracellular cholesterol ester were detected by enzyme -fluorescence. PPAR -γ, ACAT1 mRNA and protein expressions were determined by RT - PCR and Western blotting, respectively. RESULTS： THP - 1 -derived macrophages infected with C. pn at concentration of 5 × 10^5 and 1 × 10^6 IFU resulted in the large accumulation of lipid droplets and the ratio of cholesteryl ester （CE） to total cholesterol （TC） was much higher than 50% when co - incubated with low density lipoprotein （LDL）. C. pn up - regulated the expressions of ACAT1 mRNA and protein, and down - regulated the expressions of PPAR γ mRNA and protein in a concentration- dependent manner （P 〈0. 05 ）. Rosiglitazone （10, 20 μmol/L） markedly suppressed the accumulation of lipid droplets and CE by C. pn. Moreover, rosiglitazone inhibited the up - regulation of ACAT1 mRNA and protein expression by C. pn infection in a concentration -dependent manner （P 〈0.05 ）. CONCLUSION： C. pn induces macrophage foam cell formation by up - regulating ACAT1 expression via PPARγ pathway, which may provide new evidences for the development and progression of atherosclerosis initiated by C. pn infection.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2009年第7期1312-1318,共7页
Chinese Journal of Pathophysiology
基金
湖北省自然科学基金资助项目(No.2006ABA105)
作者简介
通讯作者 Tel：027-85351551；E-mail：chengbei81@yahoo．com．cn
