High-Dose Naproxen Aggravates Pancreatic Fibrosis in a Rat Model of Chronic Pancreatitis
High-Dose Naproxen Aggravates Pancreatic Fibrosis in a Rat Model of Chronic Pancreatitis
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DOI：
10.1097/mpa.0b013e3181bb90b5
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发表时间：
2010-04
期刊：
影响因子：
2.9
通讯作者：
Wei Zhang;Jun Gao;T. Zhao;Wenbin Wu;Yu Bai;D. Zou;Zhaoshen Li
中科院分区：
文献类型：
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作者：
Wei Zhang;Jun Gao;T. Zhao;Wenbin Wu;Yu Bai;D. Zou;Zhaoshen Li
目的：非甾体抗炎药（NSAIDs）被广泛用于治疗慢性胰腺炎（CP）疼痛。本研究旨在探讨非甾体抗炎药对三硝基苯磺酸诱导的慢性前列腺炎大鼠炎症和纤维化进展的影响。方法：采用三硝基苯磺酸胰管内灌注法复制大鼠慢性胰腺炎模型。在诱导CP后2周开始给予萘普生治疗（20和40 mg/kg口服[PO]和腹腔内），持续3周。采用胰腺组织学、货车Gieson染色和羟脯氨酸含量评价胰腺损伤和纤维化。此外，还研究了萘普生对伤害性反射行为和血清肿瘤坏死因子浓度的影响，并进行了胰腺平滑肌肌动蛋白的免疫组织化学分析。结果：高剂量（40 mg/kg）纳洛酮组大鼠胰腺胶原含量和β-平滑肌肌动蛋白表达均高于对照组（P < 0.05）。口服高剂量萘普生可加重胰腺纤维化和炎症反应（P < 0.05）。高剂量萘普生对CP大鼠的热戒断反应无镇痛作用，但能显著降低热戒断反应的潜伏期（P < 0.05）。结论：高剂量萘普生治疗（40 mg/kg PO）加重了CP大鼠的胰腺纤维化，并发挥了致痛作用，这表明在CP临床实践中长期使用NSAID作为镇痛剂的潜在风险。
Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for the treatment of pain in chronic pancreatitis (CP). This study aimed to investigate the effect of NSAIDs on the inflammation and fibrosis progression in trinitrobenzene sulfonic acid-induced CP rats. Methods: Chronic pancreatitis was induced by trinitrobenzene sulfonic acid infusion into rat pancreatic ducts. Naproxen treatment (20 and 40 mg/kg per os [PO] and intraperitoneally) started 2 weeks after the induction of CP for 3 weeks. Histological analysis of the pancreas, Van Gieson staining, and contents of hydroxyproline were used to evaluate pancreatic damage and fibrosis. Furthermore, the effect of naproxen on nociceptive reflective behaviors and serum tumor necrosis factor &agr; concentration were studied, and immunohistochemical analysis of &agr;-smooth muscle actin in the pancreas was performed. Results: Pancreatic collagen content and &agr;-smooth muscle actin expression were higher in the CP group treated with high-dose (40 mg/kg PO) naproxen (P < 0.05). High-dose naproxen administered orally aggravated pancreatic fibrosis and inflammation (P < 0.05). Instead of playing an analgesic role, high-dose naproxen decreased the thermal withdrawal latencies in CP rats (P < 0.05). Conclusions: High-dose naproxen treatment (40 mg/kg PO) aggravated pancreatic fibrosis in CP rats and played an algogenic role that suggests the potential risk of long-term use of NSAIDs as analgesic in clinical practice with CP.