Grup de Recerca en Patologia Pancreàtica Exocrina, Hospital Universitari Vall d'Hebron, Institut de Recerca, Universitat Autònoma de Barcelona, CIBER-EHD, Barcelona, Spain.
Am J Physiol Gastrointest Liver Physiol. 2011 Nov;301(5):G846-55. doi: 10.1152/ajpgi.00485.2010. Epub 2011 Aug 18.
Tocotrienols exhibit anti-inflammatory properties over macrophages and promote cytotoxicity in activated pancreatic stellate cells, suggesting that they may limit chronic pancreatitis progression. We aimed to quantitate the effect of oral tocotrienols on a rat model of chronic pancreatic injury. Chronic-like pancreatitis was induced by repeated arginine pancreatitis. Palm oil tocotrienol-rich fraction (TRF) was given by gavage before and after pancreatitis inductions. Amylase and hydroxyproline were determined in pancreatic homogenates; collagen, fibronectin, α-smooth muscle actin (SMA), glial fibrillary acidic protein (GFAP), and phosphorylated Smad3 were assessed by Western blotting. Transforming growth factor (TGF)-β1 was measured in plasma. Morphological assessment included light microscopy, fibrosis area fraction, and collagen network fractal analysis. Arginine pancreatitis induced pancreatic atrophy and increased hydroxyproline that ameliorated after TRF. Arginine increased TGF-β1 (185 ± 40 vs. 15 ± 2 ng/ml; P <0.01) that was blunted by TRF (53 ± 19; P < 0.01). TRF reduced protease and Smad3 activation, collagen, and fibronectin. α-SMA increased and GFAP diminished in arginine pancreatitis, consistent with long-term stellate cell activation, and TRF reverted these changes to basal. Arginine pancreatitis increased fibrosis area fraction (4.5 ± 0.3% vs. 0.2 ± 0.2%), collagen network complexity (fractal dimension 1.52 ± 0.03 vs. 1.42 ± 0.01; P < 0.001), and inhomogeneity (lacunarity 0.63 ± 0.03 vs. 0.40 ± 0.02; P < 0.001), which were all reduced by TRF (1.3 ± 0.4%, 1.43 ± 0.02%, and 0.51 ± 0.03%, respectively; P < 0.01). Best correlation coefficients were obtained when comparing fibrosis area fraction with lacunarity (r = 0.88) and both parameters with pancreatic weight (r = -0.91 and -0.79, respectively). TRF administered only before pancreatitis best, but not fully, recapitulated the beneficial effects of TRF. Tocotrienols improve quantitative measures of chronic pancreatic damage. They may be of benefit in human chronic pancreatitis.
生育三烯酚具有抗炎作用，可以促进激活的胰腺星状细胞的细胞毒性，这表明它们可能限制慢性胰腺炎的进展。我们旨在定量研究口服生育三烯酚对慢性胰腺损伤大鼠模型的影响。通过反复精氨酸胰腺炎诱导慢性样胰腺炎。在胰腺炎诱导前后通过灌胃给予富含生育三烯酚的棕榈油馏分（TRF）。在胰腺匀浆中测定淀粉酶和羟脯氨酸；通过 Western 印迹法评估胶原、纤维连接蛋白、α-平滑肌肌动蛋白（SMA）、胶质纤维酸性蛋白（GFAP）和磷酸化 Smad3。测量血浆中的转化生长因子（TGF）-β1。形态学评估包括光镜检查、纤维化面积分数和胶原网络分形分析。精氨酸胰腺炎诱导胰腺萎缩和羟脯氨酸增加，TRF 后改善。精氨酸增加 TGF-β1（185 ± 40 对 15 ± 2 ng/ml；P <0.01），TRF 使其降低（53 ± 19；P < 0.01）。TRF 减少蛋白酶和 Smad3 激活、胶原和纤维连接蛋白。精氨酸性胰腺炎中α-SMA 增加，GFAP 减少，表明长期星状细胞激活，TRF 使这些变化恢复到基础水平。精氨酸性胰腺炎增加纤维化面积分数（4.5 ± 0.3%对 0.2 ± 0.2%）、胶原网络复杂性（分形维数 1.52 ± 0.03 对 1.42 ± 0.01；P < 0.001）和不均匀性（腔隙率 0.63 ± 0.03 对 0.40 ± 0.02；P < 0.001），TRF 降低这些参数（分别为 1.3 ± 0.4%、1.43 ± 0.02%和 0.51 ± 0.03%；P < 0.01）。纤维化面积分数与腔隙率（r = 0.88）和两个参数与胰腺重量（r = -0.91 和 -0.79）的相关性最好。仅在胰腺炎前给予生育三烯酚可最大程度地但不完全地重现生育三烯酚的有益作用。生育三烯酚可改善慢性胰腺损伤的定量指标。它们可能对人类慢性胰腺炎有益。
