Advances in medical sciences · 2023
Effect and mechanism of pirfenidone combined with 2-methoxy-estradiol perfusion through portal vein on hepatic artery hypoxia-induced hepatic fibrosis.
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Zheng Hui, Huang Ning, Lin Jun-Qing, Yan Le-Ye, Jiang Qing-Gui, Yang Wei-Zhu
Аннотация
PURPOSE: The aim of this study was to explore the effect and mechanism of pirfenidone (PFD) combined with 2-methoxyestradiol (2-ME2) perfusion through portal vein on hepatic artery hypoxia-induced hepatic fibrosis.
MATERIALS AND METHODS: Sprague-Dawley rats were divided into 5 groups (n = 3/group): control group, hepatic artery ligation (HAL) group, HAL + PFD (portal vein perfusion of PFD) group, HAL+2-ME2 (portal vein perfusion of 2-ME2) group and HAL + PFD+2-ME2 group depending on whether they received HAL and/or portal vein perfusion (PFD and/or 2-ME2). Livers were harvested for pathology, western blotting (WB), and quantitative real-time PCR (qRT-PCR).
RESULTS: Sirius red staining showed that portal vein perfusion of drugs resulted in degradation of liver fibrosis. Immunohistochemistry showed decreased hypoxia-inducible factor-1 α (HIF-1α) and α-smooth muscle actin (α-SMA) after portal intravenous drugs infusion compared with HAL group (P < 0.05). WB analysis showed increased Smad7 in HAL + PFD group compared with HAL group (P < 0.05). qRT-PCR analysis showed decreased matrix metallo-proteinase 2 (MMP2), transforming growth factor β1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1), and Collagen I mRNA in HAL + PFD group except for tissue inhibitor of metalloproteinase-1 (TIMP-1) compared with HAL group (P < 0.05). Compared with HAL + PFD group, the addition of 2-ME2 did not lead to better results in qRT-PCR analysis.
CONCLUSIONS: The portal vein perfusion of PFD significantly reduced the hepatic artery hypoxia-induced fibrosis degree in treated rats by down-regulating the expression of HIF-1α, α-SMA, MMP2, TGF-β1, MCP-1, and Collagen I, as well as up-regulating the TIMP-1 expression and Smad7 protein level. Combined 2-ME2 infusion was not better than PFD alone.
MATERIALS AND METHODS: Sprague-Dawley rats were divided into 5 groups (n = 3/group): control group, hepatic artery ligation (HAL) group, HAL + PFD (portal vein perfusion of PFD) group, HAL+2-ME2 (portal vein perfusion of 2-ME2) group and HAL + PFD+2-ME2 group depending on whether they received HAL and/or portal vein perfusion (PFD and/or 2-ME2). Livers were harvested for pathology, western blotting (WB), and quantitative real-time PCR (qRT-PCR).
RESULTS: Sirius red staining showed that portal vein perfusion of drugs resulted in degradation of liver fibrosis. Immunohistochemistry showed decreased hypoxia-inducible factor-1 α (HIF-1α) and α-smooth muscle actin (α-SMA) after portal intravenous drugs infusion compared with HAL group (P < 0.05). WB analysis showed increased Smad7 in HAL + PFD group compared with HAL group (P < 0.05). qRT-PCR analysis showed decreased matrix metallo-proteinase 2 (MMP2), transforming growth factor β1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1), and Collagen I mRNA in HAL + PFD group except for tissue inhibitor of metalloproteinase-1 (TIMP-1) compared with HAL group (P < 0.05). Compared with HAL + PFD group, the addition of 2-ME2 did not lead to better results in qRT-PCR analysis.
CONCLUSIONS: The portal vein perfusion of PFD significantly reduced the hepatic artery hypoxia-induced fibrosis degree in treated rats by down-regulating the expression of HIF-1α, α-SMA, MMP2, TGF-β1, MCP-1, and Collagen I, as well as up-regulating the TIMP-1 expression and Smad7 protein level. Combined 2-ME2 infusion was not better than PFD alone.