Division of Field Medicine, Department of Internal Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China.
Pancreas. 2010 Apr;39(3):293-300. doi: 10.1097/MPA.0b013e3181bb90b5.
: 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.
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 alpha concentration were studied, and immunohistochemical analysis of alpha-smooth muscle actin in the pancreas was performed.
Pancreatic collagen content and alpha-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).
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.
非甾体抗炎药（NSAIDs）广泛用于治疗慢性胰腺炎（CP）的疼痛。本研究旨在探讨 NSAIDs 对三硝基苯磺酸诱导的 CP 大鼠炎症和纤维化进展的影响。
通过向大鼠胰管内输注三硝基苯磺酸诱导 CP，2 周后开始用萘普生（20 和 40 mg/kg 口服[PO]和腹腔内）治疗 3 周。胰腺组织学分析、Van Gieson 染色和羟脯氨酸含量用于评估胰腺损伤和纤维化。此外，研究了萘普生对伤害性反射行为和血清肿瘤坏死因子-α浓度的影响，并对胰腺中α-平滑肌肌动蛋白进行了免疫组织化学分析。
用高剂量（40 mg/kg PO）萘普生治疗的 CP 组胰腺胶原含量和α-平滑肌肌动蛋白表达更高（P < 0.05）。口服高剂量萘普生加重了 CP 大鼠的胰腺纤维化和炎症（P < 0.05）。高剂量萘普生并没有发挥镇痛作用，反而降低了 CP 大鼠的热退缩潜伏期（P < 0.05）。
高剂量萘普生（40 mg/kg PO）治疗加重了 CP 大鼠的胰腺纤维化，并发挥了致痛作用，这表明在 CP 患者的临床实践中，长期使用 NSAIDs 作为镇痛药存在潜在风险。
