标题：GSK-3β抑制剂LiCl干预大鼠重症急性胰腺炎的量效关系

      作者：陈辰，赵凯亮，邓文宏，余佳，郭闻一，张大兴，王卫星
    (武汉大学人民医院肝胆腔镜外科消化系统疾病湖北省重点实验室，湖北武汉430060)

      卷次： 2016年27卷9期

      【摘要】目的探讨糖原合成酶激酶-3β (GSK-3β)抑制剂氯化锂(LiCl)干预大鼠重症急性胰腺炎(SAP)的量效关系。方法50 只SPF 级雄性Wistar 大鼠，按数字表法随机分为五组(n=10)：假手术组(SO 组)、重症急性胰腺炎组(SAP 组)、LiCl 40 mg/kg 组、60 mg/kg 组和80 mg/kg 预处理组(LiCl 组)。胆胰管逆行注射5%牛磺胆酸钠溶液(0.1 mL/100 g)制备SAP大鼠模型；SO组在胆胰管内注射等量生理盐水替代牛磺胆酸钠。LiCl 组造模前30 min 经股静脉注射相应浓度LiCl。术后12 h 分批处死大鼠，检测血清淀粉酶(AMY)、谷丙转氨酶(ALT)、肌酐(Cr)、腹水量和肺湿干比。光镜下观察胰腺组织病理学变化并进行病理学评分。结果SAP组大鼠AMY、ALT、Cr、腹水量、肺湿干比、胰腺病理评分均较SO 组升高[(7 224.14±1 872.41) U/L vs (1 780.21±231.12) U/L、(250.56±51.56) U/L vs(98.45±10.36) U/L、(85±19) U/L vs (36±4) U/L、(11.05±2.76) g vs (0.33±0.04) g、(3.21±0.61) vs (1.60±0.20)、(11.52±1.23)分vs (0.54±0.02) 分]，差异均具有统计学意义(P<0.05)；LiCl 60 mg/kg 组上述指标与SAP 组相比较均有下降[(4 215.36±940.24) U/L vs (7 224.14±1 872.41) U/L、(160.25±35.39) U/L vs (250.56±51.56) U/L、(50±11) U/L vs(85±19) U/L、(6.04±1.03) g vs (11.05±2.76) g、(2.70±0.54) vs (3.21±0.61)、(9.03±1.09)分vs (11.52±1.23)分]，差异均有统计学意义(P<0.05)；而LiCl 40 mg/kg组AMY、腹水量、肺湿干比以及胰腺病理评分与SAP组比较差异均无统计学意义(P>0.05)；LiCl-80 mg/kg组大鼠的ALT升高大于SAP组[(312.47±69.41) U/L vs (250.56±51.56) U/L]，差异有统计学意义(P<0.05)，Cr 水平与SAP组比较[(79±17) U/L vs (85±19) U/L]差异无统计学意义(P>0.05)。结论LiCl-60 mg/kg是干预重症急性胰腺炎大鼠模型最佳有效剂量。
      【关键词】Wistar大鼠；重症急性胰腺炎；氯化锂；剂量-效应关系
      【中图分类号】R-332 【文献标识码】A 【文章编号】1003—6350（2016）09—1380—03D

ose-effect relationship of LiCl, an inhibitor of GSK-3β, on severe acute pancreatitis in rats.
CHEN Chen, ZHAOKai-liang, DENG Wen-hong, YU Jia, GUO Wen-yi, ZHANG Da-xing, WANG Wei-xing. Department of Hepatobiliary andLaparoscopic Surgery, Renmin Hospital of Wuhan University, Key Laboratory of Hubei Province for Digestive System Diseases,Wuhan 430060, Hubei, CHINA【Abstract】Objective To investigate dose-effect relationship of LiCl, an inhibitor of GSK-3β, on severe acutepancreatitis in rats. Methods Fifty male Wistar rats were randomly divided into 5 groups (n=10) by digital table method:sham operation group (SO group), severe acute pancreatitis model group (SAP group), different dosage LiCl pretreatmentgroups (40 mg/kg, 60 mg/kg and 80 mg/kg). SAP model was induced by retrograde infusion of 5% sodium taurocholate(0.1 mL/100 g) into the biliopancreatic duct. In SO group, the same amount of normal saline (NS) was infused intobilio-pancreatic duct instead of sodium taurocholate. Various doses (40 mg/kg, 60 mg/kg and 80 mg/kg) of LiCl solutionwere administered via femoral vein 30 min before the SAP induction in LiCl pretreatment groups. Rats were killedat 12 h after operation, and the levels of serum amylase (AMY), alanine transarninase (ALT), creatinine (Cr), ascites,lung wet/dry weight ratio were measured in all groups. Pancreatic tissue was observed under the light microscope andpathological score was evaluated. Results The levels of AMY, ALT, Cr, ascites, lung wet/dry weight ratio, and pancreaticpathological score in SAP group were significantly higher than those in SO groups (7 224.14±1 872.41) U/L vs(1 780.21±231.12) U/L, (250.56±51.56) U/L vs (98.45±10.36) U/L, (85±19) U/L vs (36±4) U/L, (11.05±2.76) g vs (0.33±0.04) g,(3.21±0.61) vs (1.60±0.20), (11.52±1.23) vs (0.54±0.02) (P<0.05). Compared with SAP group, 60 mg/kg dosage of LiCl hadthe best effect on improving all the indexes [(4 215.36±940.24) U/L vs (7 224.14±1 872.41) U/L, (160.25±35.39) U/L vs(250.56±51.56) U/L, (50±11) U/L vs (85±19) U/L, (6.04±1.03) g vs (11.05±2.76) g, (2.70±0.54) vs (3.21±0.61), (9.03±1.09)vs (11.52±1.23), P<0.05], while 40 mg/kg dosage of LiCl failed to improve some indexes (AMY, ascites, lung wet/dryweight ratio, pathological score) (P>0.05). However, ALT level of LiCl 80 mg/kg group was higher than SAP group[(312.47±69.41) U/L vs (250.56±51.56) U/L, P<0.05], and there was no significant difference of Cr level between thetwo groups [(79±17) U/L vs (85±19) U/L, P>0.05]. Conclusion LiCl (60 mg/kg) administered intravenously was theoptimal and effective dosage for attenuating the severity of severe acute pancreatitis.【Key words】Wistar rat; Severe acute pancreatitis; LiCl; Dose-response relationship