花姜酮通过NF-κB保护重症急性胰腺炎大鼠胰腺损伤

Protective Effect of Zerumbone on Pancreatic Injury in Severe Acute Pancreatitis via NF-kB

目的探讨花姜酮对重症急性胰腺炎大鼠胰腺损伤可能的保护作用,为重症急性胰腺炎防治提供理论依据。方法 70只Wistar大鼠,雄性,按照随机数字表法随机分为4组,即正常对照组(NC组,n=10)、重症急性胰腺炎组(SAP组,n=40)、花姜酮预处理组(ZER组,n=10)及花姜酮药物对照组(ZER-CON组,n=10),SAP组又分为建模后1、3、6及12 h 4个时间点组(n=10)。SAP组及ZER组大鼠采用胆胰管逆行注射5%硫磺胆酸钠溶液(0.1 m L/100 g)制备SAP模型,NC组及ZER-CON组则向胆胰管注入等量生理盐水。ZER组及ZER-CON组于模型制备前30 min由股静脉穿刺给予10 mg/kg的花姜酮溶液。NC组、ZER组及ZER-CON组于建模后12 h处死大鼠,SAP组分别于建模后1、3、6及12 h处死大鼠。分别观察各组大鼠的死亡情况,测定其腹水量、血清淀粉酶(AMY)和磷脂酶A2水平;光镜下观察胰腺组织的病理学改变;采用免疫组化法检测各组大鼠胰腺组织中核因子-κB(Nuclear Factor-kappa B,NF-κB)p65的表达。结果 ZER-CON组大鼠的死亡情况、腹水量、AMY及磷脂酶A2水平和胰腺组织的病理学评分以及NF-κB p65蛋白表达与NC组相近,其差异均无统计学意义(P>0.05);SAP组上述指标均明显高于NC组(P<0.05)。ZER组组大鼠的上述指标与SAP组相比明显降低(P<0.05),但均高于NC组(P<0.05)。结论应用花姜酮可以减少SAP大鼠的死亡,减少腹水量,减轻胰酶及胰腺病理学损伤,同时可降低胰腺NF-κB p65蛋白的表达。提示花姜酮可能通过核因子NF-κB途径对SAP大鼠胰腺起保护作用。

Objective To investigate the possible protective effect of zerumbone on pancreatic injury in severe acute pancreatitis （SAP） rats, and to provide a theoretical basis for prevention and treatmen of severe acute pancreatitis. Methods Seventy male Wistar rats were randomly divided into four groups： normal control group （NC group, n=10）, SAP group （n=40）, Zerumbone pretreatment group （ZER group, n=10）, and Zerumbone drug control group （ZER- CON group, n=10）. Rats of SAP group were divided into four time points of 1 h, 3 h, 6 h, and 12 h （n=10 each time point）. SAP models were induced by retrograde injection of 5% sodium taurocholate （0.1 mL/100 g） in biliopancreatic duct in SAP group and ZER group. Rats were injected isotonic saline solution instead of taurocholate as a control m Nt~ group and ZER-CON group. Zerumbone solution （10 mg/kg） was administered via femoral vein half an hour prior to establishing models in ZER group and ZER-CON group. All rats except SAP group were sacrificed at 12 h time point after the induction of SAP. The rats in SAP group were sacrificed at 1 h, 1 h, 3 h, 6 h and 12 h time point after induction of SAP. The mortality, ascites, serum amylase （AMY）, phospholipase, and pathological examination of pancreas were observated or detected. The expression of nuclear factor-kappa B （NF-KB） p65 in pancreatic tissues was evaluated by immunohistochemistry assay. Results There were no difference of the levels of mortality, ascites, serum AMY, phospholipase, pathological examination, and NF-KB p65 location expression of pancreas between the ZER-CON group and NC group （P〉0.05）. The above indexes in SAP group were significantly higher than those in NC group （P〈0.05）. However, those in ZER group were significantly lower than in SAP group （P〈0.05）, and higher than in NC group （P〈0.05）. Conclusions Zerumbone can reduce the mortality and ascites, effectively alleviate the enzyme, pathological injury, and NF-KB p65 location expression in pancreatic tissue following SAP. It may indicate that zerumbone can protect pancreatic injury in SAP via NF-KB pathway.