摘要
目的:探讨塞来昔布对大鼠重症急性胰腺炎(severe acute pancreatitis,SAP)治疗效果及机制.方法:SD大鼠共135只,其中75只随机平均分为SAP组,低剂量及高剂量塞来昔布组,观察其生存率;60只SD大鼠随机平均分为对照组(假手术组),SAP组,低剂量及高剂量塞来昔布组.胆胰管内注射牛磺胆酸钠溶液造模,ELISA法检测大鼠血清TNF-α、IL-1β及IL-6的表达;RT-PCR检测胰腺组织COX-2mRNA的表达;HE染色、胰腺组织半定量积分评价胰腺病理学改变.结果:塞来昔布可降低大鼠SAP的病理损害积分,高剂量组在造模后的24h可显著减低组织水肿(2.28±0.30vs2.73±0.22,P<0.05);在12和24h均可显著降低腺泡坏死(2.03±0.15vs2.48±0.24,2.09±0.10vs2.65±0.25,均P<0.05)及炎性细胞浸润(1.80±0.22vs2.51±0.17,1.57±0.26vs2.20±0.22,均P<0.05).造模后COX-2mRNA表达及TNF-α、IL-1β及IL-6产生增加,塞来昔布治疗组上述检测指标明显低于SAP组(均P<0.05),且随塞来昔布剂量的增加其抑制作用逐渐增强.塞来昔布高剂量治疗组可显著提高大鼠SAP的生存率(16%vs52%,P<0.05).结论:塞来昔布可能通过抑制TNF-α、IL-1β及IL-6的表达,改善胰腺局部病理改变及预后.
AIM： To investigate the efficacy of celecoxib in the treatment of severe acute pancreatitis （SAP） in rats and explore potential mechanisms involved.
METHODS： A total of 135 Sprague-Dawley rats were used in this study, of which 75 were randomly and equally divided into three groups （SAP model control group, low-dose and highdose celecoxib treatment groups） to investigate the survival rate, and 60 were randomly and equally divided into four groups （sham operation group, SAP model control group and low-dose and high-dose celecoxib treatment groups） to detect pancreatic histopathological changes, serum tumor necrosis factor-α （TNF-α）, interleukin-1β （IL-1β） and interleukin-6 （IL-6）levels, and pancreatic expression of cyclooxygenase-2 （COX-2）. SAP was induced in rats by retrograde injection of sodium taurocholate into the biliopancreatic duct. The histopathological changes in the pancreas of rats were evaluated using a semi-quantitative scoring method. The changes in serum TNF-α, IL-1β and IL-6 levels at different time points were measured by enzymelinked immunosorbent assay （ELISA）. The expression of COX-2 mRNA in the pancreas was detected by reverse transcription-polymerase chain reaction （RT-PCR）.
RESULTS： Celecoxib ameliorated pancreatic pathological damage in SAP rats. High-dose celecoxib could signifi cantly mitigate edema at 24 hours （2.28 ± 0.30 vs 2.73 ± 0.22, P 〈 0.05）, acinar necrosis at 12 and 24 hours （2.03 ± 0.15 vs 2.48 ± 0.24 and 2.09 ± 0.10 vs 2.65 ± 0.25, respectively; both P 〈 0.05）, and inflammatory cell infiltration at 12 and 24 hours （1.80 ± 0.22 vs 2.51 ± 0.17 and 1.57 ± 0.26 vs 2.20 ± 0.22, respectively; both P 〈 0.05）. The levels of serum TNF-α, IL-1β and IL-6 in SAP rats were signifi cantly higher than those in normal control mice at all time points. After celecoxib treatment, the levels of serum TNF-α, IL-1β and IL-6 signif icantly decreased in SAP rats, especially prominent in the high-dose group （P 〈 0.
出处
《世界华人消化杂志》
CAS
北大核心
2009年第31期3197-3202,共6页
World Chinese Journal of Digestology
