Endogenous miR-21 and TIMP-1 Regulate Hepatic Injury and Fibrosis by Bile Duct Ligation in Vivo

2021 ◽  
Author(s):  
Chung-Hsin Lee ◽  
Yi-Chin Yang ◽  
Yi-Wen Hung ◽  
Ching-Chang Cheng ◽  
Yen-Chung Peng
Keyword(s):  
Bile Duct ◽  
Large Scale ◽  
Bile Duct Ligation ◽  
Inflammatory Responses ◽  
Histopathological Examination ◽  
Sprague Dawley ◽  
Functional Protein ◽  
Common Bile Duct Ligation ◽  
Simvastatin Treatment ◽  
Duct Ligation

Abstract TIMP metallopeptidase inhibitor 1 (TIMP-1) has been identified as a multifunctional molecule with divergent functions. It participates in wound healing and regeneration, cell morphology and survival, tumor metastasis, angiogenesis, and inflammatory responses. An imbalance of Matrix Metalloproteinase/TIMP regulation has been implicated in several inflammatory diseases. TIMP-1 could be considered an important regulator in the process of liver fibrosis and bile duct degeneration. Thus, we aimed to determine the role of TIMP-1 in a rat model of Common Bile Duct Ligation (CBDL). Male Sprague-Dawley rats were divided into several groups, including those with/ without CBDL surgery and those with/without amiodarone or simvastatin administration. Amiodarone/simvastatin treatment was given at a daily dose of 15 mg/kg and 18 mg/kg by means of intergalactic gavage, which began 7 days prior to CBDL induction. Two weeks after surgery, the animals in each group were sacrificed and hepatocyte degeneration severity was examined using histological morphologies. Large-scale array for secretory factors is intended for the purpose of finding key functional protein after CBDL. The hepatic level of miR-21 was determined through Taqman miRNA analysis. Furthermore, the TIMP-1 level in liver tissue was also visualized by histological stain. Liver injury and fibrosis were founded in CBDL rats based upon histopathological examination and serum biochemical analysis. Hepatic miR-21 and TIMP-1 were significantly up-regulated in CBDL rats, while being slightly rescued in response to amiodarone or simvastatin treatment. Up-regulation of miR-21 and TIMP-1 may result in the progression of hepatic cirrhosis after bile duct obstruction. Drug intervention for cirrhosis, like the use of statin, may function via similar mechanisms.

Partial Ligation of the Common Bile Duct Results in Reversible Cholestasis in Rats

2016 ◽  
Vol 101 (5-6) ◽  
pp. 249-256 ◽  
Author(s):  
Jun Jiang ◽  
Dongzheng Li ◽  
Jishu Wei ◽  
Kuirong Jiang ◽  
Yi Miao
Keyword(s):  
Bile Duct ◽  
Common Bile Duct ◽  
Bile Salt ◽  
Bile Duct Ligation ◽  
Serum Biochemistry ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Common Bile Duct Ligation ◽  
Ductular Reaction ◽  
Duct Ligation

The animal model of common bile duct ligation is very toxic; therefore, the aim of this study was to establish a new model of obstructive jaundice in rats with partial common bile duct obstruction. Male Sprague-Dawley rats were subjected to a sham operation or partial ligation of bile duct procedure. Serum biochemistry, liver histology, and expression of bile salt transporters were examined after surgery. Serum levels of aspartate aminotransferase, alkaline phosphatase, total bilirubin, and bile acids were significantly increased in the partial bile duct ligation group 3 days after surgery. However, these changes spontaneously normalized within 14 days after surgery in the partial bile duct ligation group compared with the sham group. Bile infarcts, ductular reaction, and abundant hepatocyte turnover were detected exclusively in the partial bile duct ligation group on postoperative day 3. However, these changes dramatically reversed 14 days after surgery. Bile salt transporter expression was significantly decreased at day 3 and gradually recovered in the following 2 weeks. In conclusion, the current rat model of obstructive cholestasis is reversible, representing the clinical characteristics of partial biliary obstruction, and may be used to investigate the effects of various therapeutic strategies on reversible acute cholestasis.

scholarly journals Pathophysiology of Lung Injury Induced by Common Bile Duct Ligation in Mice

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e94550 ◽  
Author(s):  
Fumiaki Shikata ◽  
Tomohisa Sakaue ◽  
Koh-ichi Nakashiro ◽  
Mikio Okazaki ◽  
Mie Kurata ◽  
...  
Keyword(s):  
Bile Duct ◽  
Common Bile Duct ◽  
Lung Injury ◽  
Bile Duct Ligation ◽  
Common Bile Duct Ligation ◽  
Duct Ligation

scholarly journals A new model of reversible obstructive jaundice using rapidly absorbable suture materials

2012 ◽  
Vol 35 (6) ◽  
pp. 351 ◽  
Author(s):  
Nurettin Kahramansoy ◽  
Hayri Erkol ◽  
Edip E Yilmaz ◽  
Mustafa Şit ◽  
Fahri Yilmaz ◽  
...  
Keyword(s):  
Bile Duct ◽  
Common Bile Duct ◽  
Obstructive Jaundice ◽  
Surgical Intervention ◽  
Bile Duct Ligation ◽  
Absorbable Suture ◽  
Suture Materials ◽  
Common Bile Duct Ligation ◽  
Duct Ligation ◽  
Morphologic Changes

Purpose: Reversible obstructive jaundice models have some limiting features, including the need for a second anaesthesia, re-laparotomy and surgical intervention after common bile duct ligation. The present study investigates the feasibility of a new application that can eliminate these limitations. Rapidly absorbable suture materials were used for ligation; therefore, spontaneous biliary decompression was anticipated by the self release of these rapidly degrading materials. Methods: Common bile ducts in Wistar Albino rats were ligated with silk, polyglytone 6211, or irradiated polyglactine 910 (n=7 for each group). Rats were grouped according to both the suture materials and the experiments termination date: 5 days (sham, silk5, polyglytone5, polyglactine5) and 21 days (silk21, polyglytone21, polyglactine21) after the ligation. Biochemical and morphologic changes of liver were assessed. Results: The group polyglactine21 showed significantly lower mean ALT, AST, GGT, total and direct bilirubin values when compared with the group polyglactine5 (p=0.004-0.037). Morphologic changes did not correlate with the biochemical amelioration. In the group polyglytone21, not only the biochemical but also the morphologic changes significantly ameliorated when compared with the group polyglytone5 (p=0.003-0.043). No procedure associated mortality was observed. Conclusion: Common bile duct ligation with polyglytone offers a new reversible model for prolonged obstructive jaundice which abolishes the need for relaparotomy and a second surgical intervention and significantly reduces mortality.

Characterization of inducible nature of MRP3 in rat liver

2000 ◽  
Vol 278 (3) ◽  
pp. G438-G446 ◽  
Author(s):  
Kotaro Ogawa ◽  
Hiroshi Suzuki ◽  
Tomoko Hirohashi ◽  
Toshihisa Ishikawa ◽  
Peter J. Meier ◽  
...  
Keyword(s):  
Bile Duct ◽  
Common Bile Duct ◽  
Protein Level ◽  
Bile Duct Ligation ◽  
Organic Anion ◽  
Mrna Level ◽  
Common Bile Duct Ligation ◽  
Sd Rats ◽  
Anion Transporter ◽  
Duct Ligation

We found previously that expression of multidrug resistance-associated protein (MRP) 3 is induced in a mutant rat strain (Eisai hyperbilirubinemic rats) whose canalicular multispecific organic anion transporter (cMOAT/MRP2) function is hereditarily defective and in normal Sprague-Dawley (SD) rats after ligation of the common bile duct. In the present study, the inducible nature of MRP3 was examined, using Northern and Western blot analyses, in comparison with that of other secondary active [Na+-taurocholic acid cotransporting polypeptide (Ntcp), organic anion transporting polypeptide 1 (oatp1), and organic cation transporter (OCT1)] and primary active [P-glycoprotein (P-gp), cMOAT/MRP2, and MRP6] transporters. α-Naphthylisothiocyanate treatment and common bile duct ligation induced expression of P-gp and MRP3, whereas expression of Ntcp, oatp1, and OCT1 was reduced by the same treatment. Although expression of MRP3 was also induced by administration of phenobarbital, that of cMOAT/MRP2, MRP1, and MRP6 was not affected by any of these treatments. Moreover, the mRNA level of MRP3, but not that of P-gp, was increased in SD rats after administration of bilirubin and in Gunn rats whose hepatic bilirubin concentration is elevated because of a defect in the expression of UDP-glucuronosyl transferase. However, the MRP3 protein level was not affected by bilirubin administration. Although the increased MRP3 mRNA level was associated with the increased concentration of bilirubin and/or its glucuronides in mutant rats and in SD rats that had undergone common bile duct ligation or α-naphthylisothiocyanate treatment, we must assume that factor(s) other than these physiological substances are also involved in the increased protein level of MRP3.

Chondroitin sulfate protects liver in the experimental model of extra-hepatic cholestasis induced by common bile duct ligation

2017 ◽  
Vol 66 (1) ◽  
pp. S389
Author(s):  
P.L.R. Guedes ◽  
M.L. Gazarini ◽  
M.Y. Icimoto ◽  
J.A. Aguiar ◽  
M. Kouyoumdjian ◽  
...  
Keyword(s):  
Bile Duct ◽  
Common Bile Duct ◽  
Chondroitin Sulfate ◽  
Experimental Model ◽  
Bile Duct Ligation ◽  
Common Bile Duct Ligation ◽  
Duct Ligation
Sign in / Sign up

Export Citation Format

Share Document