摘要
目的观察过氧化物酶体增殖物活化受体γ（PPARγ）的天然配体l5d-PGJz对HSC增殖及活化的影响，以探讨PPARγ在HSC活化过程中的作用。方法采用MTT法和RT—PCR方法观察5mol／L及10μol／L15d-PGJ2对体外培养的HSC自发活化及血小板衍生生长因子（PDGF）引起的HSC增殖及活化的影响。结果以5μmol／L15d-PGJ2处理原代HSC3d后，可明显抑制HSC活化标志物α平滑肌肌动蛋白的表达，而PPARγ的表达较未处理组明显增高（0．64±0．03对比0．09±0．01，t=36．0517，P〈0．01）;15d-PGJ2可剂量依赖性地抑制PDGF引起的HSC增殖;经5μmol／L和10μmol／L 15d-PGJ2预处理后再用PDGF干预，则PPARY的表达较单用PDGF干预组明显增高（分别为0．03±0．02对比0．60±0．03，t=42．6616，P〈0．01;以及0．03±0．02对比0．69±0．04，t=33．83，P〈0．01），而HSC的活化指标α-平滑肌肌动蛋白、αI（I）型胶原及单核细胞趋化蛋白-1的表达则受抑制。结论激活PPARγ可调控HSC的促纤维化和促炎症作用，促进PPARγ的表达可能成为抗肝纤维化的新手段。
Objective To observe the effect of ligand of peroxisome proliferators-activated receptor gamma （PPAR gamma） 15d-PGJ2 on the proliferation and activation of hepatic stellete cells （HSC） and to study the role played by PPAR gamma during the process of HSC activation. Methods By using RT-PCR and cell culture, we investigated the effects of 5 μmol/L and 10 μmoi/L 15d-PGJ2 on culture-activated HSC and on PDGF-induced HSC profiferation, production of extracellular matrix and expression of chemokines. Results The expression of alpha-SMA was significantly suppressed by 5 μmol/L 15d-PGJ2, and the expres- sion of PPAR gamma was significantly higher in the 15d-PGJ2 treated group than in the untreatexi group （0.64±0.03 vs 0.09 ± 0.01, t = 36.0517, P 〈 0.01）; PDGF-induced HSC proliferation was dose-dependently suppressed by 15d-PGJ2; the expressions of PPAR gamma in 5 μ mol/L and also in 10 μmol/L 15d--PGJ2 plus PDGF pre-treated group increased much more than those in the PDGF-treated group （0.03 ± 0.02 vs0.60±0.03, t = 42.6616, P〈 0.01 and 0.03±0.02 vs 0.69 ± 0.04, t = 33.83, P〈 0.01）; the expressions ofalpha-SMA, alpha I （I）-coUagen and MCP-I wege supptessed.Conclusion Activation of PPAR gamma can modulate pro-fibrotic and pro-inflammatory roles of HSC and the increased expression of PPAR gamma may become a new target for antifibrosis.
出处
《中华肝脏病杂志》
CAS
CSCD
北大核心
2007年第2期114-117,共4页
Chinese Journal of Hepatology
