Vitamin E attenuates biochemical and morphological features associated with development of chronic pancreatitis
Vitamin E attenuates biochemical and morphological features associated with development of chronic pancreatitis
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DOI：
10.1152/ajpgi.00333.2003
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发表时间：
2004-07-01
影响因子：
4.5
通讯作者：
Malagelada, JR
中科院分区：
文献类型：
--
作者：
Gómez, JA;Molero, X;Malagelada, JR
目的是研究维生素E对雨蛙肽（Cr）诱导的胰腺炎大鼠使用环孢素A（CsA）后胶原蛋白沉积的影响。环孢素A使雨蛙肽诱导的完全可再生、自限性的胰腺炎转变为一种类似慢性疾病，同时伴有转化生长因子（TGF）-β增加和成肌纤维细胞增殖。维生素E抑制系膜细胞中TGF -β的释放并降低环孢素A的细胞毒性。Wistar大鼠每日接受环孢素A（20 mg/kg），并在第1天和第8天诱导雨蛙肽胰腺炎（雨蛙肽 + 环孢素A组）。在另一组中，从环孢素A使用前4天开始给予维生素E（600 mg·kg⁻¹·d⁻¹）。另外三组分别单独给予溶媒、环孢素A或雨蛙肽。在动物处死当天（第15天）采集血浆，测定硫代巴比妥酸反应物（TBARS）、8 - 异前列腺素和透明质酸。称取胰腺重量并进行处理用于光学显微镜检查，以评估结缔组织和成肌纤维细胞数量。还测定胰腺匀浆中的胶原蛋白（羟脯氨酸）和TBARS含量。环孢素A组和雨蛙肽 + 环孢素A组大鼠的TBARS、8 - 异前列腺素和TGF -β升高。维生素E治疗大大降低了这些指标。维生素E还减轻了雨蛙肽 + 环孢素A组胰腺重量的下降。雨蛙肽 + 环孢素A组大鼠的胰腺羟脯氨酸和血浆透明质酸增加，但维生素E可有效降低它们。形态学显示，维生素E治疗的大鼠纤维化评分改善，成肌纤维细胞数量减少。维生素E在实验性慢性胰腺炎的发展过程中降低氧化应激和胶原蛋白沉积。辅助抗氧化剂在慢性胰腺炎的治疗中可能有价值。
The objective was to investigate the effects of vitamin E on collagen deposition induced by Cyclosporin A (CsA) administration in rats with caerulein (Cr) pancreatitis. CsA transforms the fully regenerative, self-limited form of Cr pancreatitis into a chroniclike disease in conjunction with increased transforming growth factor (TGF)-beta and myofibroblast proliferation. Vitamin E inhibits TGF-beta release in mesangial cells and reduces CsA cytotoxicity. Wistar rats received CsA daily (20 mg/kg), and CR pancreatitis was induced on days 1 and 8 (Cr + CsA group). In a separate group, vitamin E (600 mg.kg(-1).day(-1)) was administered starting 4 days before CsA. Three other groups received either vehicle, CsA, or Cr alone. Thiobarbituric acid-reactive substance (TBARS), 8-isoprostanes, and hyaluronic acid were measured in plasma obtained on the day the animals were killed (day 15). Pancreases were weighed and processed for light microscopy to assess connective tissue and myofibroblast number. Pancreatic homogenates were also assayed for collagen ( hydroxyproline) and TBARS content. TBARS, 8-isoprostane, and TGF-beta were elevated in CsA and Cr + CsA rats. Vitamin E treatment greatly decreased these parameters. Vitamin E also decreased the fall in pancreatic weight observed in Cr + CsA pancreas. Pancreatic hydroxyproline and plasma hyaluronic acid were increased in Cr + CsA rats but were effectively reduced by vitamin E. Morphology showed improvement in fibrosis score and a decreased number of myofibroblasts in vitamin E-treated rats. Vitamin E reduces oxidative stress and collagen deposition during the development of experimental chronic pancreatitis. Adjuvant antioxidants may be of value in the treatment of chronic pancreatitis.