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目的 探讨过氧化物酶体增殖因子活化受体γ(PPARγ)在急性心肌炎发病中的作用;PPARγ配体治疗能否减轻心肌炎及其可能的机制。方法 6周龄雄性Lewis大鼠24只诱导自身免疫性心肌炎,随机分为阳性对照、15d-PGJ2治疗组及比格列酮治疗组(各组8只),正常大鼠8只作为正常对照。观察PPARγ配体15 d-PGJ2 注射(200 μg·kg-1·d-1)和比格列酮口服(10 mg·kg-1·d-1)治疗对心肌炎症程度的影响;免疫组化检测心肌PPARγ表达、免疫杂交检测IκBα、IL-1β和TNFα蛋白表达;核酸酶保护法检测心肌组织促炎细胞因子mRNA表达、电泳迁移率变动分析检测NF-κB的DNA结合活性。结果 ①PPARγ在炎症心肌组织中表达增强,主要定位在炎性浸润细胞的核和核周围区;②15d-PGJ2和比格列酮治疗使心肌炎症得到减轻,心重／体重、炎症分级严重程度明显减轻;③PPARγ配体15d-PGJ2和比格列酮治疗明显降低心肌组织中多种炎性细胞因子mRNA表达,及降低心肌内上调的IL-1β和TNFα蛋白表达;④与正常对照组相比,心肌炎阳性对照组心肌NF-κB的DNA结合活性增加5.6倍,15d-PGJ2和比格列酮治疗降低增强的NF-κB结合活性。⑤心肌炎阳性对照组心肌细胞核内NF-κB抑制物IκB蛋白含量明显降低;与心肌炎组相比,15d-PGJ2和比格列酮治疗分别增加IκB蛋白含量2.2?
Objective To investigate the role of peroxisome proliferator-activated receptor gamma (PPARγ) in the pathogenesis of acute myocarditis and whether PPARγ ligand treatment can reduce myocarditis and its possible mechanism. Methods Twenty-four male Lewis rats at 6 weeks of age were induced by autoimmune myocarditis. The rats were randomly divided into positive control, 15d-PGJ2 treatment group and 8 mice in each group. Eight normal rats were used as normal control. The effect of PPARγ ligand on the inflammatory degree of myocardium was observed by 15 d-PGJ2 injection (200 μg · kg-1 · d-1) and oral administration of 10 mg · kg-1 · d-1 The expression of PPARγ was detected by immunohistochemistry. The expressions of IκBα, IL-1β and TNFα were detected by immunocytochemistry. The mRNA expression of proinflammatory cytokines was detected by nuclease protection assay. The DNA binding activity of NF-κB was detected by electrophoretic mobility shift assay. Results ① The expression of PPARγ was enhanced in inflammatory myocardium and mainly localized in the nucleus and perinuclear area of inflammatory infiltrating cells. ② The myocardial inflammation was relieved with 15d-PGJ2 and the treatment with begglitazone, the severity of heart weight / body weight and inflammation were significantly reduced; ③ The PPARγ ligand 15d-PGJ2 and beglitazone treatment significantly decreased the mRNA expression of multiple inflammatory cytokines in myocardium and decreased the expression of IL-1β and TNFα in myocardium; ④ Compared with the normal control group, the positive myocarditis The DNA-binding activity of NF-κB increased by 5.6-fold in the control group, and 15d-PGJ2 and the treatment with pioglitazone reduced the enhanced NF-κB-binding activity. ⑤ The content of IκB protein of NF-κB inhibitor in myocardium positive control group was significantly lower than that in myocarditis group. Compared with myocarditis group, the content of IκB protein increased by 2.2% and 15d-PGJ2 respectively