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首页> 外文期刊>Current therapeutic research, clinical and experimental. >Effects of Silymarin and Pentoxifylline on Matrix Metalloproteinase-1 and -2 Expression and Apoptosis in Experimental Hepatic Fibrosis
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Effects of Silymarin and Pentoxifylline on Matrix Metalloproteinase-1 and -2 Expression and Apoptosis in Experimental Hepatic Fibrosis

机译：水飞蓟素和己酮可可碱对实验性肝纤维化中基质金属蛋白酶-1和-2表达及凋亡的影响

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BACKGROUND: Many therapeutic strategies have been proposed to treat liver fibrosis, but no drugs have been proved effective. Matrix metalloproteinases (MMPs) have been reported to play a role in some cellular cascades of hepatic inflammation and fibrosis.OBJECTIVE: The purpose of this study was to investigate whether silymarin and pentoxifylline (PTX) have hepatoprotective and antifibrotic effects in experimental hepatic fibrosis.METHODS: Sprague-Dawley rats were divided into 4 groups: silymarin group (silymarin 4 mg/kg centre dot d~(-1) orally, common bile duct ligation [CBDL]); PTX group (PTX 2 mg/kg centre dot d~(-1) intraperitoneally, CBDL); sham group (common bile duct [CBD] exploration only); and control group (saline 1 mL/d orally, CBDL). The CBD was explored and dissected sufficiently to allow passage of a 3/0 silk suture via midline laparotomy. On day 10, all animals were euthanized via cervical dislocation. Then, 5-cm~3 liver samples from the right lobe were removed for histomorphologic evaluation and 3-mL blood samples were taken via cardiac puncture for biochemical analyses. Apoptosis was determined using the terminal deoxynucleotidyltransferase-biotin nick end-label (TUNEL) staining method. Plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase; total and indirect bilirubin concentration; hepatic MMP-1 and -2 and tissue inhibitor of MMP (TIMP)-1 and -2 activity; and transforming-growth factor (TGF)-beta_1 concentration were measured. Collagen content was determined by measuring hydroxyproline in liver samples. Malon-dialdehyde (MDA) was used to estimate lipid peroxidation.RESULTS: Thirty-two adult male Sprague-Dawley rats were divided into 4 groups: silymarin group (n = 7), PTX group (n = 7), sham group (n = 9), and control group (n = 9). Compared with the control group (14.6 [2.44]), mean (SD) hepatocyte apoptosis (as measured by the ratio of TUNEL-positive cells) was significantly suppressed in the silymarin group (1.2 [0.13]; P = 0.001) and the PTX group (3.8 [0.34]; P = 0.001). Mean (SD) MMP-2 activity in the silymarin group (57.35 [9.89] mug/mL; P = 0.04) and the PTX group (46.88 [9.56] ug/mL; P = 0.04) was significantly lower than that observed in the control group (232.32 [79-76] mug/mL).
机译：背景：已经提出了许多治疗肝纤维化的治疗策略，但没有药物被证明有效。据报道基质金属蛋白酶（MMPs）在一些肝炎症和纤维化的细胞级联反应中起作用。目的：本研究的目的是研究水飞蓟素和己酮可可碱（PTX）在实验性肝纤维化中是否具有保肝和抗纤维化作用。 Sprague-Dawley大鼠分为4组：水飞蓟素组（水飞蓟素4 mg / kg中心点d〜（-1）口服，胆总管结扎[CBDL]）; PTX组（腹膜内PTX 2 mg / kg中心点d〜（-1），CBDL）;假手术组（仅胆总管[CBD]探查）;对照组（口服生理盐水1 mL / d，CBDL）。探索并充分剖析了CBD，以允许3/0丝线通过中线剖腹手术通过。在第10天，通过颈脱位使所有动物安乐死。然后，从右叶取出5 cm〜3的肝样本进行组织形态学评估，并通过心脏穿刺取3 mL血液样本进行生化分析。使用末端脱氧核苷酸转移酶-生物素缺口末端标记（TUNEL）染色法测定细胞凋亡。血浆天冬氨酸转氨酶（AST），丙氨酸转氨酶（ALT）和γ-谷氨酰转氨酶水平;总和间接胆红素浓度;肝MMP-1和-2以及MMP（TIMP）-1和-2活性的组织抑制剂;测定转化生长因子（TGF）-β_1的浓度。通过测量肝脏样品中的羟脯氨酸来确定胶原蛋白含量。结果：将32只成年雄性Sprague-Dawley大鼠分为4组：水飞蓟素组（n = 7），PTX组（n = 7），假手术组（n）。 = 9）和对照组（n = 9）。与对照组相比（14.6 [2.44]），水飞蓟素组（1.2 [0.13]; P = 0.001）和PTX显着抑制了平均（SD）肝细胞凋亡（以TUNEL阳性细胞的比例衡量）。组（3.8 [0.34]; P = 0.001）。水飞蓟素组（57.35 [9.89]杯子/毫升; P = 0.04）和PTX组（46.88 [9.56] ug / mL; P = 0.04）的平均（SD）MMP-2活性显着低于在对照组（232.32 [79-76]杯/毫升）。

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