A Novel Rabbit Model for Benign Biliary Stricture Formation and the Effects of Medication Infusions on Stricture Formation

Yang, Qin; Wang, Junke; Li, Fu Yu; Ma, Wen‐Jie; Hu, Hai‐Jie; Ran, Cong-Dun; Pan, Qiuwei

doi:10.1007/s10620-018-5118-0

Cited by 7 publications

(3 citation statements)

References 31 publications

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“…Through Masson staining, we found a large number of collagen fibers and smooth muscle fibers in the anastomotic stoma 1 month after the operation, and the fibers were disorderly and broken. The characteristics of scar formation in CJS are as follows (39)(40)(41): inflammatory cell infiltration and fibroblast activation appeared in the early stage of anastomotic stoma healing; with time, infiltration of inflammatory cells in the anastomotic stoma was gradually aggravated, fibroblasts and myofibroblasts proliferated, and collagen fibers and smooth muscle fibers increased significantly, and eventually led to the proliferation of granulation tissue and scar formation. If an early intervention can reduce the anastomosis's inflammatory reaction and the activation of fibroblasts, it could prevent CJS scars' formation.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of scar formation following Roux-en-Y choledochojejunostomy in a novel rat model of obstructive jaundice

Lyu¹,

Wang²,

Zhou³

et al. 2021

Ann Transl Med

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Background:The present study aimed to analyze the scar formation mechanism following Roux-en-Y choledochojejunostomy (CJS) in a novel rat model of obstructive jaundice. Methods:The biliary obstruction model of Sprague-Dawley (SD) rats was established in advance, and 24 rats were randomly divided into 4 groups (control group, 1-day ligation group, 3-day ligation group, and 5-day ligation group). Changes in postoperative weight, common bile duct diameter, and laboratory indexes were analyzed to determine the best operation time. Roux-en-Y CJS in rats was studied based on the model, and the rats were randomly divided into 4 groups [control group, 3-day choledochojejunostomy (CJS) group, 7-day CJS group, and 30-day CJS group]. The same indexes were analyzed, and the characteristics of scar formation were evaluated by histopathology and polymerase chain reaction examination.Results: The third day after common bile duct ligation is the best time for a Roux-en-Y CJS. The common bile duct diameter expands to 4.2 mm on average, and these physiological characteristics are consistent with current standard clinical findings. After completing CJS, the rats' weight returned to normal levels, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), direct bilirubin (DB), and C-reactive protein (CRP) indexes gradually decreased (P<0.05). Anastomotic stoma diameter tended to narrow with time and was significantly narrower on day 30 than preoperation. After CJS, the expression of α-smooth muscle actin (α-SMA) peaked in the early stage and was still higher than that of the control group in the bile duct wall 1 month postoperatively (P<0.05). Transforming growth factor-β1 (TGF-β1) expression gradually increased and was higher than that of the control group at each stage postoperatively (P<0.05). Conclusions:The rat Roux-en-Y CJS model is more in line with our surgical model, and the clinical condition has potential applicability for the study of CJS scar formation. Scar formation following CJS in rats is characterized by the activation of fibroblasts caused by early inflammatory stimulation, which leads to the proliferation of collagen and smooth muscle fibers, resulting in scars.

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Section: Discussionmentioning

confidence: 99%

Mechanism of scar formation following Roux-en-Y choledochojejunostomy in a novel rat model of obstructive jaundice

Lyu¹,

Wang²,

Zhou³

et al. 2021

Ann Transl Med

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“…Thirty-eight New Zealand white rabbits weighing 2-3 kg were purchased from the Experimental Animal Center of Sichuan University and were randomly divided into three groups: proliferative cholangitis group (PC group, n =16); antibiotic therapy group (AT, n=16); sham-operated group (SO group, n =6). The animal model of CPC was generated for PC and AT groups as previously described [ 23 , 24 ]. Briefly, the rabbit's duodenal wall was punctured with a 26-gauge needle and then a 5-0 nylon thread was inserted into the common bile duct through the duodenal papilla.…”

Section: Methodsmentioning

confidence: 99%

Effective Treatment of Chronic Proliferative Cholangitis by Local Gentamicin Infusion in Rabbits

Yang

et al. 2018

BioMed Research International

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Background Hepatolithiasis is highly prevalent in East Asia characterized by the presence of gallstones in the biliary ducts of the liver. Surgical resection is the potentially curative treatment but bears a high risk of stone recurrence and biliary restenosis. This is closely related to the universal presence of chronic proliferative cholangitis (CPC) in the majority of patients. Recent evidence has indicated the association of bacterial infection with the development of CPC in hepatolithiasis. Thus, this study aims to investigate the feasibility and efficacy of local infusion of gentamicin (an antibiotic) for the treatment of CPC in a rabbit model. Methods The rabbit CPC model was established based on previously published protocols. Bile duct samples were collected from gentamicin-treated or control animals for pathological and molecular characterization. Results Histologically, the hyperplasia of biliary epithelium and submucosal glands were inhibited and the thickness of the bile duct wall was significantly decreased after gentamicin therapy. Consistently, the percentage of proliferating cells marked by ki67 was significantly reduced by the treatment. More importantly, this treatment inhibited interleukin 2 production, an essential inflammatory cytokine, and the enzyme activity of endogenous β-Glucuronidase, a key factor in the formation of bile pigment. Conclusions Local gentamicin infusion effectively inhibits the inflammation, cell proliferation, and lithogenesis in a rabbit model of CPC. This approach represents a potential treatment for CPC and thus prevents recurrent hepatolithiasis.

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“…Although its exact mechanism of action has not been established yet, it is suggested that it acts by decreasing the production rate of TGFβ‐1 (the growth factor beta), TNFα (tumor necrosis factor alpha), and IL‐1β (Interleukin‐1 beta) in the in vitro and in vivo fibrotic disease models . Despite the use of pirfenidone in primarily pulmonary fibrosis, as well as the experimental studies using it in the disorders manifesting with fibrosis—including the cutaneous scars, vocal fold scars, abdominal adhesions, intestinal and esophageal strictures, and benign biliary strictures—the number of studies on tracheal stenosis is limited …”

Section: Introductionmentioning

confidence: 99%

Prevention of tracheal stenosis with pirfenidone after tracheotomy: An experimental study

Türkmen

Pata

2018

The Laryngoscope

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Objectives In this study, pirfenidone's role about reducing tracheal stenosis by suppressing fibrosis and inflammation was examined. Methods Tracheotomy was performed on 14 rats, and their cannulas were fixed to tracheotomy area by stoma suture. Two working groups were established. Rats in the first group were given 15 mg/kg/day (1 mL pirfenidone solution) pirfenidone intraperitoneally for 10 days. In the second group as a control group, 1 mL saline solution was applied intraperitoneally. Ten days later, rats were decanulated and kept alive for 3 more weeks. Anesthetized rats were sacrificed on day 30. All rat tracheas were resected between the first and seventh rings. Epithelial damage, inflammation, and fibrosis were determined histopathologically; diameters of intratracheal lumen and their mucosal thickness parameters were determined histomorphometrically; and TGFβ‐1 (the growth factor beta), TNFα (tumor necrosis factor alpha), and IL‐1β (Interleukin‐1 beta) values were determined immunohistochemically. Results According to the parameters of the control group, fibrosis; diameters of intratracheal lumen; and values of TGFβ‐1, TNFα, and IL‐1β were found to be statistically significant. Conclusion In our study, it was found that pirfenidone reduces fibrosis and narrowing of intratracheal lumen diameter significantly. Level of Evidence NA Laryngoscope, 129:E178–E186, 2019

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A Novel Rabbit Model for Benign Biliary Stricture Formation and the Effects of Medication Infusions on Stricture Formation

Cited by 7 publications

References 31 publications

Mechanism of scar formation following Roux-en-Y choledochojejunostomy in a novel rat model of obstructive jaundice

Mechanism of scar formation following Roux-en-Y choledochojejunostomy in a novel rat model of obstructive jaundice

Effective Treatment of Chronic Proliferative Cholangitis by Local Gentamicin Infusion in Rabbits

Prevention of tracheal stenosis with pirfenidone after tracheotomy: An experimental study

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