PMID- 36610261
OWN - NLM
STAT- MEDLINE
DCOM- 20230414
LR  - 20230414
IS  - 1898-4002 (Electronic)
IS  - 1896-1126 (Linking)
VI  - 68
IP  - 1
DP  - 2023 Mar
TI  - Effect and mechanism of pirfenidone combined with 2-methoxy-estradiol perfusion 
      through portal vein on hepatic artery hypoxia-induced hepatic fibrosis.
PG  - 46-53
LID - S1896-1126(22)00044-X [pii]
LID - 10.1016/j.advms.2022.12.001 [doi]
AB  - 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 
      alpha (HIF-1alpha) and alpha-smooth muscle actin (alpha-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 
      beta1 (TGF-beta1), 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-1alpha, alpha-SMA, MMP2, TGF-beta1, 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.
CI  - Copyright (c) 2022 Medical University of Bialystok. Published by Elsevier B.V. All 
      rights reserved.
FAU - Zheng, Hui
AU  - Zheng H
AD  - Department of Interventional Radiology, Fujian Medical University Union Hospital, 
      Fuzhou, Fujian, People's Republic of China.
FAU - Huang, Ning
AU  - Huang N
AD  - Department of Interventional Radiology, Fujian Medical University Union Hospital, 
      Fuzhou, Fujian, People's Republic of China.
FAU - Lin, Jun-Qing
AU  - Lin JQ
AD  - Department of Interventional Radiology, Fujian Medical University Union Hospital, 
      Fuzhou, Fujian, People's Republic of China.
FAU - Yan, Le-Ye
AU  - Yan LY
AD  - Department of Interventional Radiology, Fujian Medical University Union Hospital, 
      Fuzhou, Fujian, People's Republic of China.
FAU - Jiang, Qing-Gui
AU  - Jiang QG
AD  - Department of Interventional Radiology, Fujian Medical University Union Hospital, 
      Fuzhou, Fujian, People's Republic of China; Department of Interventional Therapy, 
      Xiamen Humanity Hospital, Xiamen, Fujian, People's Republic of China.
FAU - Yang, Wei-Zhu
AU  - Yang WZ
AD  - Department of Interventional Radiology, Fujian Medical University Union Hospital, 
      Fuzhou, Fujian, People's Republic of China. Electronic address: 
      yangwz2022@163.com.
LA  - eng
PT  - Journal Article
DEP - 20230105
PL  - Netherlands
TA  - Adv Med Sci
JT  - Advances in medical sciences
JID - 101276222
RN  - 0 (Transforming Growth Factor beta1)
RN  - D7NLD2JX7U (pirfenidone)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 6I2QW73SR5 (2-Methoxyestradiol)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *Hepatic Artery/metabolism
MH  - *Portal Vein/metabolism
MH  - Transforming Growth Factor beta1/adverse effects/metabolism
MH  - Matrix Metalloproteinase 2
MH  - Tissue Inhibitor of Metalloproteinase-1/genetics
MH  - 2-Methoxyestradiol/pharmacology/therapeutic use
MH  - Rats, Sprague-Dawley
MH  - Liver Cirrhosis/drug therapy
MH  - Fibrosis
MH  - Perfusion
MH  - Hypoxia
MH  - Collagen
OTO - NOTNLM
OT  - 2-methoxyestradiol
OT  - Hepatic fibrosis
OT  - Hypoxia
OT  - Pirfenidone
OT  - Portal vein perfusion
COIS- Declaration of competing interest The authors declare no conflict of interests.
EDAT- 2023/01/08 06:00
MHDA- 2023/04/14 06:41
CRDT- 2023/01/07 18:14
PHST- 2022/06/01 00:00 [received]
PHST- 2022/09/20 00:00 [revised]
PHST- 2022/12/07 00:00 [accepted]
PHST- 2023/04/14 06:41 [medline]
PHST- 2023/01/08 06:00 [pubmed]
PHST- 2023/01/07 18:14 [entrez]
AID - S1896-1126(22)00044-X [pii]
AID - 10.1016/j.advms.2022.12.001 [doi]
PST - ppublish
SO  - Adv Med Sci. 2023 Mar;68(1):46-53. doi: 10.1016/j.advms.2022.12.001. Epub 2023 
      Jan 5.