罗格列酮对大鼠重症急性胰腺炎并发肾损伤的保护作用

Protective effect of rosiglitazone in the treatment of the rats with severe acute pancreatitis and acute kidney injury

目的研究罗格列酮(ROSI)对大鼠重症急性胰腺炎(SAP)并发急性肾损伤(AKI)的肾保护作用及其对核因子相关因子2(Nrf2)/抗氧化反应元件(ARE)转导通路的调节。方法将45只SD大鼠随机分为假手术组、模型组和实验组,每组15只。用4%牛磺胆酸钠逆行胰胆管注射方法建立大鼠ASP并发AKI模型。假手术组在切开腹腔后,仅翻动十二指肠及胰腺。于造模前30 min,实验组经腹腔注入10 mg·kg-1ROSI,假手术组和模型组均予以等量0.9%NaCl。用自动生化仪测定血清中淀粉酶(AMS)、尿素氮(BUN)和肌酸酐(Cr)的表达,用Western blotting法测定肾组织中Nrf2、血红素加氧酶l(HO-1)、蛋白依赖还原型辅酶/Ⅱ醌氧化还原酶1(NQO1)蛋白表达。结果实验组、假手术组和模型组的AMS分别为(3007.45±127.53),(902.35±46.82)和(3562.86±165.37)U·L^(-1),BUN分别为(10.62±1.64),(7.84±1.53)和(17.74±1.85)mmol·L^(-1),Cr分别为(102.83±11.26),(59.76±9.84)和(156.47±13.73)μmol·L^(-1),Nrf2蛋白分别为(1.58±0.10),(0.57±0.05)和(1.05±0.07),HO-1蛋白分别为(2.29±0.14),(0.54±0.43)和(1.05±0.08),NQO1蛋白分别为(1.56±0.09),(0.59±0.03)和(1.01±0.06),实验组和模型组的上述指标比较,差异均有统计学意义(均P<0.05)。结论 ROSI对大鼠ASP并发AKI具有肾保护作用,其作用机制可能与Nrf2/ARE信号通路上调HO-1和NQO1蛋白的表达有关。

Objective To investigate the protective effect of rosiglitazone（ ROSI） in the treatment of the rats with severe acute pancreatitis（ SAP） and acute kidney injury（ AKI）,and its influence on nuclear factor related factor 2/antioxidant response element（ Nrf2/ARE） pathway.Methods Fourty-five SD rats were randomly divided into sham-operation,model and test groups with 15 cases per group. The rat model of SAP combined with AKI was established by retrograde injection of 4% sodium taurocholate into the pancreaticobiliary duct. After abdominal cavity incision,Sham-operation group were only turned the duodenum and pancreas. 30 min before the establishment of model,test group was given 10 mg·kg^-1 ROSI with intraperitoneal injection,sham-operation and model groups were given the same amount of 0. 9% NaCl. Theexpression of serum amylase（ AMS）,blood urea nitrogen（ BUN） and creatinine（ Cr） in serum were measured by automatic biochemical analyzer. The expression of nuclear factor related factors 2（ Nrf2）,heme oxygenase 1（ HO-1）and quinone oxidoreductase 1（ NQO1） in renal tissue were measured by Western blotting. Results The AMS of test,Sham-operation and model groups were（ 3007. 45 ± 127. 53）,（ 902. 35 ± 46. 82） and（ 3562. 86 ± 165. 37） U·L^-1,BUN were（ 10. 62 ± 1. 64）,（ 7. 84 ± 1. 53） and（ 17. 74 ± 1. 85） mmol · L^-1,Cr were（ 102. 83 ± 11. 26）,（ 59. 76 ± 9. 84） and（ 156. 47 ± 13. 73） μmol · L^-1,Nrf2 protein were（ 1. 58 ± 0. 10）,（ 0. 57 ± 0. 05） and（ 1. 05 ± 0. 07）,HO-1 protein were（ 2. 29 ± 0. 14）,（ 0. 54 ± 0. 43） and（ 1. 05 ± 0. 08）,NQO1 protein were（ 1. 56 ± 0. 09）,（ 0. 59 ± 0. 03） and（ 1. 01 ± 0. 06）,the differences were statistically significant between test group and model group（ all P〈0. 05）. Conclusion ROSI has a renal protective effect on SAP combined with AKI in rats,and its mechanism may be related to the up regulation of HO-1 and NQO1 protein expression in Nrf2/ARE signaling pathway.