N-乙酰半胱氨酸预防重症急性胰腺炎的实验研究

Experimental Study on N-acetylcysteine for Prevention of Severe Acute Pancreatitis

背景:还原型谷胱甘肽(GSH)是细胞内最重要的非酶类抗氧化剂,各种急性胰腺炎(AP)动物模型均存在腺泡细胞GSH耗竭。目的:探讨N-乙酰半胱氨酸(NAC)对重症急性胰腺炎(SAP)的预防作用及其可能机制。方法:54只健康雄性Wistar大鼠随机分为3组,正常对照组予假手术,AP模型组和NAC预处理组胰胆管逆行注射牛磺胆酸钠以模拟人类SAP,NAC预处理组于造模前30 min腹腔注射NAC。分别于术后3 h、6 h、12 h检测血清Ca2+、丙二醛(MDA)和胰腺组织GSH,透射电子显微镜(TEM)观察胰腺组织超微结构。结果:术后3 h、6 h至12 h,各组血清Ca2+浓度、胰腺组织GSH含量逐渐降低,血清MDA水平逐渐升高。NAC预处理组各时点血清Ca2+浓度、胰腺组织GSH含量均显著高于AP模型组(P<0.05),血清MDA水平显著低于AP模型组(P<0.05)。TEM观察显示AP模型组腺泡细胞胞质内可见大量空泡,酶原颗粒分泌、排出明显减少;NAC预处理组空泡体积较小,酶原颗粒排出增加。结论:NAC可在SAP早期恢复腺泡细胞的GSH含量,通过抗氧化作用减轻腺泡细胞的氧化损伤,维持细胞内钙平衡,改善酶原颗粒的转运和排泌,从而对SAP的发展产生预防作用。

Background： Reduced glutathione （GSH）, the most important cellular nonenzymatic antioxidant, is found to be depleted in acinar ceils of various experimental acute pancreatitis （AP） models. Aims： To investigate the preventive effect of N-acetylcysteine （NAC） on severe acute pancreatitis （SAP） and its possible mechanism. Methods： Fifty-four healthy male Wistar rats were randomly divided into three groups. Rats in normal control group received only sham operation, while rats in AP model group and NAC pretreatment group received retrograde cholangiopancreatic duct injection of sodium taurocholate to mimic human SAP. NAC was given intraperitoneally in NAC pretreatment group 30 minutes before operation. Serum calcium, serum malondialdehyde （MDA） and pancreatic GSH were measured 3, 6 and 12 hours after operation, respectively; the uhrastructure of pancreas was examined by transmission electron microscopy （TEM）. Results： Serum calcium and pancreatic GSH decreased gradually, while serum MDA increased gradually 3, 6, and 12 hours after operation. Serum calcium and pancreatic GSH were significantly higher, while serum MDA was significantly lower in NAC pretreatment group than in AP model group at each time point （ P 〈 0. 05 ）. TEM revealed large amount of vesicles and reduced secretion and discharge of zymogen granules in the cytoplasm of acinar cells in AP model group; while in NAC pretreatment group the cytoplasmic vesicles were relatively less and the discharge of zymogen granules were increased. Conclusions ： NAC pretreatment can restore the level of GSH in acinar cells in the early phase of SAP. It exerts antioxidant effect and preventing the progression of SAP by attenuating the oxidative damages, maintaining the calcium homeostasis and improving the transport and excretion of zymogen granules in acinar cells.