Zhang Qian, Shang Meng-Meng, Ling Qu-Fei, Wu Xiao-Ping, Liu Chun-Yu
College of Pharmaceutical Sciences, Soochow University, 199 Ren'ai road, Suzhou, 215123, People's Republic of China.
School of Biology & Basic Medical Sciences, Soochow University, Suzhou, People's Republic of China.
Arch Pharm Res. 2021 Aug;44(8):1-12. doi: 10.1007/s12272-014-0445-y. Epub 2014 Jul 30.
This study investigates the hepatoprotective effects and the potential therapeutic mechanisms of loach (Misgurnus anguillicaudatus) lyophilized powder (MLP) on dimethylnitrosamine (DMN) induced liver fibrosis in rats. After treatment with MLP (50, 100, 200 mg/kg), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), total protein (TP) and hydroxyproline (Hyp) levels were detected, to assess the destruction of hepatocytes and the extent of liver fibrosis. Matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), hyaluronic acid (HA), Laminin (LN), procollagen type-III (PC-III), collagen type-IV (C-IV), and transforming growth factor-β (TGF-β) contents in serum were all tested using ELISA kits. Alpha-smooth muscle actin (α-SMA) and the tissue inhibitor of metalloproteinase-1 (TIMP-1) protein contents and distribution were evaluated using western blot and immunohistochemical analysis. MLP significantly decreased the serum concentrations of ALT, AST, Hyp, HA, LN, PC-III, C-IV, MMP-2, TIMP-1, α-SMA and TGF-β, while increasing the contents of Alb and MMP-9. No significant changes on TP serum concentrations were observed. These results suggest that MLP has anti-hepatic fibrosis effects and its mechanism may be associated with the attenuation of extracellular matrix (ECM) synthesis, the acceleration of ECM degradation, inhibition of hepatic stellate cells (HSCs) activation and TGF-β expression.
本研究探讨泥鳅冻干粉(MLP)对二甲基亚硝胺(DMN)诱导的大鼠肝纤维化的保肝作用及潜在治疗机制。用MLP(50、100、200mg/kg)处理后,检测丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、白蛋白(Alb)、总蛋白(TP)和羟脯氨酸(Hyp)水平,以评估肝细胞的破坏情况和肝纤维化程度。使用ELISA试剂盒检测血清中基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PC-Ⅲ)、Ⅳ型胶原(C-Ⅳ)和转化生长因子-β(TGF-β)的含量。采用蛋白质印迹法和免疫组织化学分析评估α-平滑肌肌动蛋白(α-SMA)和金属蛋白酶组织抑制剂-1(TIMP-1)的蛋白含量及分布。MLP显著降低了血清中ALT、AST、Hyp、HA、LN、PC-Ⅲ、C-Ⅳ、MMP-2、TIMP-1、α-SMA和TGF-β的浓度,同时增加了Alb和MMP-9的含量。未观察到血清TP浓度有显著变化。这些结果表明,MLP具有抗肝纤维化作用,其机制可能与减少细胞外基质(ECM)合成、加速ECM降解、抑制肝星状细胞(HSCs)活化和TGF-β表达有关。