Asaumi H, Watanabe S, Taguchi M, Tashiro M, Nagashio Y, Nomiyama Y, Nakamura H, Otsuki M
Third Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Eur J Clin Invest. 2006 Feb;36(2):113-22. doi: 10.1111/j.1365-2362.2006.01599.x.
Activated pancreatic stellate cells (PSCs) play a central role in the pathogenesis of pancreatic fibrogenesis and inflammation. Ethanol, a major cause of chronic pancreatitis, directly induces PSC activation and oxidative stress. Inhibition of PSC activation or stimulation to PSC might be an effective therapeutic strategy for the prevention of pancreatic fibrosis, and (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea extracts, is a potent antioxidant of polyphenols. Therefore, we examined the mechanisms through which ethanol induces oxidative stress on PSCs and evaluated the effect of EGCG on activation and cell functions of ethanol-stimulated PSCs.
The PSCs were isolated from the pancreas of male Wister rats with Nycodenz gradient methods and cells between passages one and four were used. Isolated PSCs were cultured with ethanol (50 mM) in the absence or presence of EGCG (5 microM or 25 microM).
The EGCG pre-treatment abolished ethanol-induced lipid peroxidation of the cell membrane, loss of total superoxide dismutase (SOD) activity and suppressed ethanol-induced gene expressions of Mn- and Cu/Zn-SOD. EGCG also suppressed ethanol-induced p38 mitogen-activated protein (MAP) kinase phosphorylation, alpha-smooth muscle actin production in PSCs and activated transforming growth factor-beta1 secretion into the medium. Furthermore, EGCG inhibited ethanol-induced type-I procollagen production and collagen secretion. In addition, EGCG inhibited transformation of freshly isolated cells to activated myofibroblast-like phenotype.
Our results suggest that green tea and polyphenols could prevent pancreatic fibrosis by inhibiting PSC activation through the antioxidative effect.
活化的胰腺星状细胞（PSCs）在胰腺纤维化和炎症的发病机制中起核心作用。乙醇是慢性胰腺炎的主要病因，可直接诱导PSCs活化和氧化应激。抑制PSCs活化或刺激PSCs可能是预防胰腺纤维化的有效治疗策略，而（-）-表没食子儿茶素-3-没食子酸酯（EGCG）是绿茶提取物的主要成分，是一种有效的多酚抗氧化剂。因此，我们研究了乙醇诱导PSCs氧化应激的机制，并评估了EGCG对乙醇刺激的PSCs活化和细胞功能的影响。
采用Nycodenz梯度法从雄性Wistar大鼠胰腺中分离PSCs，使用传代1至4代的细胞。将分离的PSCs在不存在或存在EGCG（5 microM或25 microM）的情况下用乙醇（50 mM）培养。
EGCG预处理消除了乙醇诱导的细胞膜脂质过氧化、总超氧化物歧化酶（SOD）活性丧失，并抑制了乙醇诱导的Mn-和Cu/Zn-SOD基因表达。EGCG还抑制了乙醇诱导的p38丝裂原活化蛋白（MAP）激酶磷酸化、PSCs中α-平滑肌肌动蛋白的产生以及活化的转化生长因子-β1分泌到培养基中。此外，EGCG抑制了乙醇诱导的I型前胶原产生和胶原蛋白分泌。此外，EGCG抑制了新鲜分离的细胞向活化的肌成纤维细胞样表型的转化。
我们的结果表明，绿茶和多酚可以通过抗氧化作用抑制PSCs活化来预防胰腺纤维化。
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