结肠灌洗联合善宁治疗重症急性胰腺炎肝损伤的研究

Treatment of severe acute pancreatitis induced liver injury with combination of colonic irrigation and sandostatin.

目的探讨结肠灌洗治疗重症急性胰腺炎所致肝细胞损伤的保护性机制及其对肝细胞凋亡的影响。方法16只杂种犬随机分成4组:对照组、AP组、善宁治疗组和结肠灌洗加善宁治疗(联合治疗)组,每组4只。用牛磺胆酸钠+胰蛋白酶混合溶液诱导犬造成重症急性胰腺炎(SAP)模型。所有犬除术后禁食、水,常规补液外,善宁治疗为皮下每12h注射善宁0.1mg,结肠灌洗1次/d。所有犬分别于术前、12h、24h、48h、72h采取静脉血检测淀粉酶(AMY)、羟自由基OH·、丙二醛(MDA)、ALT、GST。72h后处死动物取胰腺及肝脏组织标本,用TUNEL检测肝细胞凋亡指数(AI)。结果SAP组的AMY、OH·、MDA、GST在术后12h后显著升高,ALT在术后24h显著升高,并持续至72h;联合治疗组OH·、MDA、GST和ALT均于术后24h达到高峰后开始下降,72h后下降明显,与SAP组、善宁治疗组有显著性差别(P<0.05),并且MDA值与ALT值呈正相关(模型组r=0.899,P=0.038;善宁治疗组r=0.901,P=0.037;联合治疗组r=0.83,P=0.084);联合治疗组的肝细胞凋亡指数(AI)明显低于SAP组、善宁治疗组,具有统计学差异(P<0.05),而与对照组无明显差异(P>0.05)。结论氧化应激参与了犬SAP时的肝损伤,而结肠灌洗治疗SAP肝损伤的机制之一可能是通过降低机体的自由基水平而减少氧化损伤,进而减少肝细胞的凋亡,达到保护肝脏的目的。

Objective To investigate the protective effect of colonic irrigation and sandostatin combined therapy on SAP-induced liver injury and apoptosis hepatocytes. Methods 16 hybrid dogs weighing 15 - 20 kg were equally randomized into the control group, SAP group, sandostatin group and combined treatment group. The model of SAP was established by retrograde injection of sodium taurocholate and trypsin solutions into the biliopancreatic duct in the dogs. All dogs were restrained from access to chow and water except for postoperative transfusion. The dogs in sandostatin group were treated with sandostatin 0. 1 mg per 12 h. The dogs of combined treatment group received sandostatin 0. 1 mg per 12 h plus colonic irrigation （once per 24 h）. Plasm amylase （AMY）, hydroxyl radical （OH · ）, malonaldehyde（MDA）, alanine aminotransfersae（ALT） and glutathione S-transferase （GST） were detected at different time points. Pathological change of pancreas and liver and apoptosis of hepatocytes was detected at 72 h after operation. Hepatic cell apoptosis index was detected by TUNEL method. Results AMY, OH · , MDA and GST in blood increased significantly at 12 h after operation, and ALT went up 24 h after operation till 72 h in SAP group（P 〈 0. 05）. In combined treatment group, OH · , MDA, GST and ALT reached the peak at 24 h and then began descending until 72 h, when the decrease was more significant than that in SAP group and sandostatin group （P 〈 0. 05）. In addition, a positive correlation was found between MDA and ALT. The apoptotic index of hepatocytes in combined treatment group was much lower than that in SAP and sandostatin groups （P 〈 0.05）, though it was similar to that of control group （P 〉 0. 05）. Conclusions Oxidative stress may be one of the causes for SAP-induced liver injury. Decreasing apoptosis of hepatocytes by reducing oxygen free radicals might be one of the mechanisms by which colonic irrigation and sandostatin prevent SAP-induced liver injury.