CAJ | 학술논문

目的探讨罗格列酮(Ros)干预在调节冠心病患者外周血单核细胞源性巨噬细胞(MDMs)表达核因子-κB(NF-κB)、金属蛋白酶-9(MMP-19)中的作用及可能机制.方法本研究为临床病例对照研究.于2007年3月至4月间,从湘雅二医院心内科行冠脉造影患者中,选取急性冠脉综合征患者48例(ACS组)、稳定型心绞痛(SA)患者20例(对照组)为研究对象,排除脑血管意外、急性感染和创伤、肝肾功能不全、肿瘤等患者.提取外周血单个核细胞,用巨噬细胞集落刺激因子刺激,转化为MDMs;随机分亚组后,分别用0μmol/L1μmol/L,10 μmol/L,20 μmol浓度Ros干预48h;RT-PCR检测各亚组MDMs表达过氧化物酶增殖体激活受体-γ([PPAR-γ)和MMP-9 mRNA,免疫组化法检测NF-κB P65表达强度.用ANOVA检验比较组间及亚组内MDMs在表达PPAR-γ,MMP-9,NF-κB P65的差异.结果干预前,ACS组MDMs表达PPAR-γmRNA水平低于对照组,表达NF-κB P65及MMP-9mRNA水平高于对照组;Ros干预后,ACS组及对照组PPAR-γmRNA表达明显上调,ACS组PPAR-γ的表达量与Ros浓度呈正变关系;MMP-9 mRNA表达下调,在ACs组其下调程度与Ros浓度呈反变关系;两组NF-κB P65表达量均呈现非剂量依赖性降低.结论 ACS患者外周血MDMs的PPAR-γRNA表达被抑制、NF-γB活性及MMP-9 mRNA表达增强.Ros干预可通过增加PPAR-γ的表达,从而抑制NF-κB活性和MMP-9的表达.
목적 탐토라격렬동(Ros)간예재조절관심병환자외주혈단핵세포원성거서세포(MDMs)표체핵인자-κB(NF-κB)、금속단백매-9(MMP-19)중적작용급가능궤제.방법 본연구위림상병례대조연구.우2007년3월지4월간,종상아이의원심내과행관맥조영환자중,선취급성관맥종합정환자48례(ACS조)、은정형심교통(SA)환자20례(대조조)위연구대상,배제뇌혈관의외、급성감염화창상、간신공능불전、종류등환자.제취외주혈단개핵세포,용거서세포집락자격인자자격,전화위MDMs;수궤분아조후,분별용0μmol/L1μmol/L,10 μmol/L,20 μmol농도Ros간예48h;RT-PCR검측각아조MDMs표체과양화물매증식체격활수체-γ([PPAR-γ)화MMP-9 mRNA,면역조화법검측NF-κB P65표체강도.용ANOVA검험비교조간급아조내MDMs재표체PPAR-γ,MMP-9,NF-κB P65적차이.결과 간예전,ACS조MDMs표체PPAR-γmRNA수평저우대조조,표체NF-κB P65급MMP-9mRNA수평고우대조조;Ros간예후,ACS조급대조조PPAR-γmRNA표체명현상조,ACS조PPAR-γ적표체량여Ros농도정정변관계;MMP-9 mRNA표체하조,재ACs조기하조정도여Ros농도정반변관계;량조NF-κB P65표체량균정현비제량의뢰성강저.결론 ACS환자외주혈MDMs적PPAR-γRNA표체피억제、NF-γB활성급MMP-9 mRNA표체증강.Ros간예가통과증가PPAR-γ적표체,종이억제NF-κB활성화MMP-9적표체.
Objective To investigate the effects and mechanisms of rosiglitazone on the expressions of nuclear factor-κB and matrix metalloprotease (MMP-9) in peripheral blood monocyte-derived macrophages (MDMs) in patients with coronary heart disease. Method This was a clinical case-control study. Forty-eight actue coronary symdrome (ACS) patients (ACS group), and 20 patients with stable angina (SA) (control group) were collected. They were performed coronary arteriography in the Department of Cardiology of the Second Xiangya Hospital from March to April in 2007. Exclusion criteria included acute infection, trauma or surgery patients within four weeks, cerebral vascular accident, liver and kidney dysfunction, cancer, and so on. The peripheral blood mononuclear cells were isolated and transformed into MDMs with macrophage colony-stimulating factor treatment. The transformed MDMs were randomly assigned into subgrougs and incubated with 0 /μmol/L, 1 μmol/L, 10 μmol/L, 20 μmol/L of rosiglitazone respectively. The expressions of PPAR-γ mRNA, MMP-9 mRNA were determined by RT-PCR and nuclear factor-κB P65 (NF-KB P65) expression by immunohistochemistry. Multiple comparisons were examined for significant differences using analysis of variance (ANOVA). Results The basal expression of PPAR-y mRNA was lower, in contrast, the levels of NF-KB P65 and MMP-9 mRNA were higher in ACS group than control group. PPAR-γ mRNA expression were significantly upregulated in both ACS and control groups with rosiglitazone treatment. PPAR-γ mRNA expression was positive correlation, while the expressions of MMP-9 mRNA were negative correlation with the rosiglitazone concentration in the ACS group. Rosiglitazone inhibited the expression of NF-KB in a concentration-independent manner in ACS and control groups. Conclusions The expression of PPAR-y mRNA is inhibited, while the activity of NF-KB and expression of MMP-9 mRNA are enhanced in MDMs of ACS cases. Rosiglitazone intervention may inhibit NF-KB activity and MMP-9 expression by upregulation of PPAR-y expression in MDMS of patiens with ACS.