The Role of Phospholipase D1 in Liver Fibrosis Induced by Dimethylnitrosamine In Vivo

The Role of Phospholipase D1 in Liver Fibrosis Induced by Dimethylnitrosamine In Vivo
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磷脂酶D1在二甲基亚硝胺诱导的体内肝纤维化中的作用

DOI:
10.1007/s10620-014-3130-6
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发表时间:
2014-04
影响因子:
3.1
通讯作者:
Yang, Wenzhuo
Yang, Wenzhuo
中科院分区:
医学3区
文献类型:
--
作者:
Zeng, Yu;Sun, Xianghua;Zhang, Yi;Yang, Wenzhuo

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【摘要】 研究背景磷脂酶D(PLD)已被证明参与成纤维细胞功能的调节,可能在介导器质性​​纤维化中发挥作用。目的探讨PLD对二甲基亚硝胺(DMN)诱导的大鼠肝纤维化的作用及机制。方法将55只雄性Wistar大鼠分为正常对照组、DMN模型组、N-甲基乙醇胺(MEA)对照组和MEA干预组。通过比较四组的理化指标、组织病理学、PLD活性以及纤维化相关典型标志物和细胞因子,观察PLD抑制剂MEA对大鼠肝纤维化发生发展的影响。结果伴随着PLD1表达的下调,MEA干预组与DMN模型组相比,在脾重、脾/体重指数、血清和组织生化指标、组织学指标等方面均较DMN模型组有所改善。羟脯氨酸和组织病理学。 MEA干预组TIMP1、COL1A1表达水平低于DMN模型组,MMPs表达水平高于DMN模型组。 MEA干预组PLD和PLD1活性、α-SMA表达水平显着低于DMN模型组。两组间TGF-β1、MCP1表达水平无显着差异。同时,正常对照组与MEA对照组上述参数均无显着差异。结论磷脂酶D1可能在大鼠肝纤维化的发生、发展过程中发挥重要作用。抑制PLD可能成为预防或减轻肝纤维化的新策略。
BackgroundPhospholipase D (PLD) has been proved to be involved in regulating function of fibroblasts and might play a role in mediating organic fibrosis.AimsTo investigate the role and mechanism of PLD on dimethylnitrosamine (DMN)-induced rat liver fibrosis.MethodsFifty-five male Wistar rats were divided into normal control group, DMN model group,N-methylethanolamine (MEA) control group, and MEA-intervention group. We observed the effects of MEA, a PLD inhibitor on the development and progression of rat liver fibrosis by comparing the physical and biochemical indexes, tissue pathology, PLD activity, and typical markers and cytokines related to fibrosis in the four groups.ResultsAccompanied by the down-regulation of PLD1 expression, the MEA-intervention group had improved outcomes compared with the DMN model group in terms of spleen weight, spleen/weight index, serum and tissue biochemical indexes, tissue hydroxyproline, and tissue pathology. The MEA-intervention group had lower TIMP1, COL1A1, and higher MMPs expression level than the DMN model group. The activity of PLD and PLD1, α-SMA expression level in the MEA-intervention group was much lower than those in the DMN model group. There was no significant difference between the two groups in the expression level of TGF-β1 and MCP1. Meanwhile, there were no significant differences between normal control group and MEA control group in the parameters stated above.ConclusionPhospholipase D1 may play an important role in the development and progression of rat liver fibrosis. Inhibition of PLD may become a new strategy to prevent or alleviate liver fibrosis.
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影响因子: 39.3
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