摘要
目的 探讨过氧化物酶体增殖因子活化受体 (PPARγ)在急性心肌炎发病中的作用 ;PPARγ配体治疗对急性心肌炎的影响及其可能的作用机制。方法 6周龄Lewis大鼠注射猪心肌球蛋白诱导自身免疫性心肌炎 (EAM)大鼠 36只。分为正常对照、阳性对照、15d PGJ2 治疗组及比格列酮治疗组 ,每组 9只。 2 2天后大鼠麻醉状态下开胸 ,用免疫组化法观察PPARγ在炎症心肌中的表达及PPARγ配体 15d PGJ2 注射 (2 0 0 μg·kg- 1 ·d- 1 )和比格列酮口服 (10mg·kg- 1 ·d- 1 )治疗对心肌炎症程度 ,及对致敏T细胞的增殖、活化和致心肌炎能力的影响。结果 PPARγ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 ;15d 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 ;免疫组化分析招募入炎性病灶内的CD4 + 、CD8+ 细胞和巨噬细胞数目 ,15d PGJ2 和比格列酮治疗明显减少病灶内炎性细胞浸润 :与阳性对照组相比 ,病灶内巨噬细胞(2 2± 4、2 6± 6vs 4 5± 8,分别P <0 0 1)、CD4 + 细胞 (8± 2、10± 3vs 18± 5 ,P <0 0 1)和CD8+ 细胞 (3±1、4± 2vs 7± 2 ,分别P <0 0 1和 <0 0 5 )数目明显减少。
Objective To investigate the role of peroxisome proliferator-activated receptor-γ (PPARγ) on autoimmune myocarditis, and to test the hypothesis that PPAR-γ ligands reduce experimental autoimmune myocarditis (EAM) associated with inhibition of the expansion and activation of self-sensitive T cells.Methods EAM was induced in Lewis rats by immunization with porcine cardiac myosin.Then the rats were divided into 3 groups of 9 rats: PPAR-γ ligand 15-deoxy- 12,14-PGJ 2 (15d-PGJ 2) group (15d-PGJ 2 was injected intraperitoneally at the dosage of 200 μg·kg -1·d -1), pioglitazone (PIO) group (PIO was mixed with the food and than fed at the dosage of 10 mg·kg -1·d -1), and positive control group (phosphate-buffered saline was injected intraperitoneally).Nine normal rats were used as normal controls.Three weeks later, the rats underwent thoracotomy to undergo pathologic examination.The numbers of CD4 + cells, CD8 + cells, and macrophages were calculated by microscopy.Immunohistochemistry was used to examine the location and expression of PPARγ.Western blotting was used to examine the relative amount of PPARγ protein.The proliferative response and the cytotoxicity of T cell-enriched splenocytes and lymph node cells were determined.Another rats were killed 12 days after immunization.Their spleens and lymph nodes were taken out.T-cell rich splenocytes and cells from the lymph nodes were cultured.Cardiac myosin and 15d-PGJ 2 were added.[ 3H] thymine was added 72 hours after.ELISA was used to examine the interferon-γ (IFN-γ) in the supernatant.15d-PGJ 2, PIO, or PBS were given to immunize the rats.The rats were killed 12 days after.The lymph nodes were taken out to make single cell suspension. 51Cr was used to label the cells so as to calculate the % cytotoxicity.Results All immunized rats showed myocarditis.The numbers of CD4 + cells, CD8 + T cells, and macrophages, were 18±5, 7±2, and 45±8/six 0.25 mm×0.25 mm squares. PPARγ was mainly located in the nuclear and perinuclear regi
出处
《中华医学杂志》
CAS
CSCD
北大核心
2003年第23期2067-2072,共6页
National Medical Journal of China
基金
国家自然科学基金资助项目 ( 3 0 170 3 71)
