摘要
目的探讨糖原合成酶激酶-3β(GSK-3β)抑制剂氯化锂(Li Cl)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)、Li Cl 40 mg/kg组、60 mg/kg组和80 mg/kg预处理组(Li Cl组)。胆胰管逆行注射5%牛磺胆酸钠溶液(0.1 m L/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。Li Cl组造模前30 min经股静脉注射相应浓度Li Cl。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);Li Cl 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Li Cl 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);Li Cl-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 Li Cl-60 mg/kg是干预重症急性胰腺炎大鼠模型最佳有效剂量。
Objective To investigate dose-effect relationship of Li Cl, an inhibitor of GSK-3β, on severe acute pancreatitis 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 Li Cl pretreatment groups(40 mg/kg, 60 mg/kg and 80 mg/kg). SAP model was induced by retrograde infusion of 5% sodium taurocholate(0.1 m L/100 g) into the biliopancreatic duct. In SO group, the same amount of normal saline(NS) was infused into bilio-pancreatic duct instead of sodium taurocholate. Various doses(40 mg/kg, 60 mg/kg and 80 mg/kg) of Li Cl solution were administered via femoral vein 30 min before the SAP induction in Li Cl pretreatment groups. Rats were killed at 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 and pathological score was evaluated. Results The levels of AMY, ALT, Cr, ascites, lung wet/dry weight ratio, and pancreatic pathological 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 Li Cl had the 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 Li Cl failed to improve some indexes(AMY, ascites, lung wet/dry weight ratio, pathological score)(P>0.05). However, ALT level of Li Cl 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
出处
《海南医学》
CAS
2016年第9期1380-1382,共3页
Hainan Medical Journal
基金
中央高校基本科研业务费专项资金(编号:2042015kf0086)
