大黄素对重症胰腺炎肾损伤模型大鼠血清缺氧诱导因子-1α及糖原合酶激酶-3β水平的影响

Effect of emodin on the levels of hypoxia inducible factor-1α and glycogen synthase kinase-3β in rats with severe acute pancreatitis

目的研究大黄素对重症胰腺炎肾损伤大鼠血清缺氧诱导因子-1α(HIF-1α)和糖原合酶激酶-3β(GSK-3β)水平影响。方法将60只大鼠随机分为空白组、假手术组、模型组、对照组和实验组,每组12只。模型组和试验组注入牛磺胆酸钠0.1 mL/100 g建立重症胰腺炎肾损伤大鼠模型;假手术组和对照组打开腹腔后仅轻轻翻动十二指肠以及胰腺;空白组大鼠未作任何处理。空白组、假手术组、模型组均予以腹腔注射5μL·g-10.9%Na Cl q6 h;对照组和实验组均按25μg·g-1剂量予以腹腔注射5 g·L^(-1)大黄素q6 h。术后3,6,12h,比较各组大鼠的血清肌酸酐(SCr)、尿素氮(BUN)、HIF-1α和GSK-3β水平。结果空白组、假手术组、对照组和实验组的胰腺组织病理学评分分别为(1.30±0.14),(1.39±0.14),(1.40±0.15)和(2.73±0.30)分,与模型组的胰腺组织病理学评分(9.84±1.05)分相比,差异均有统计学意义(均P<0.05),且实验组的胰腺组织病理学评分与空白组、假手术组、对照组比较,差异均有统计学意义(均P<0.05)。术后3 h,空白组、假手术组、对照组、模型组和实验组的SCr分别为(60.46±6.78),(61.52±6.78),(60.38±6.74),(120.57±13.43)和(95.35±9.85)μmol·L^(-1),BUN分别为(7.47±0.79),(8.02±0.92),(7.93±0.83),(12.49±1.53)和(8.56±0.89)mmol·L^(-1),HIF-1α分别为(225.46±23.57),(210.57±23.58),(229.67±6.74),(160.46±17.47)和(144.57±14.85)μg·L^(-1),GSK-3β分别为(6.59±0.69),(6.57±0.69),(6.74±0.68),(19.95±2.13)和(10.56±1.39)μg·L^(-1)。术后6 h,空白组、假手术组、对照组、模型组和实验组的SCr分别为(60.57±6.79),(60.55±6.76),(59.50±6.76),(143.57±15.47)和(110.57±12.55)μmol·L^(-1),BUN分别为(7.65±0.84),(8.11±0.93),(8.29±0.92),(15.46±1.64)和(12.35±1.37)mmol·L^(-1),HIF-1α分别为(226.46±24.04),(222.46±23.57),(230.57±24.05),(155.36±15.74)和(127.57±12.84)μg·L^(-1),GSK-3β分别为(6.25±0.67),(6.71±0.69),(6.82±0.71),(25.34±2.64)和(11.56±1.27)μg·L^(-1)。术后12 h,空白组、假手术组、对照组、模型组和实验组的SCr分别为(60.61±6.79),(61.68±6.79),(61.54±6.78),(166.45±17.05)和(131.45±13.46)μmol·L^(-1),BUN分别为(8.03±0.85),(7.98±0.82),(8.79±0.93),(18.66±19.46)和(15.35±1.63)mmol·L^(-1),HIF-1α分别为(219.57±23.63),(226.35±24.04),(220.25±24.04),(148.46±18.94)和(117.46±12.04)μg·L^(-1),GSK-3β分别为(6.77±0.69),(6.70±0.70),(6.86±0.70),(35.02±3.76)和(20.35±2.13)μg·L^(-1)。空白组、假手术组、对照组术后3,6,12 h的SCr、BUN、HIF-1α、GSK-3β与模型组比较,差异均有统计学意义(均P<0.05),且实验组与模型组术后3,6,12 h的SCr、BUN、HIF-1α、GSK-3β比较,差异均有统计学意义(均P<0.05)。结论大黄素可能通过上调血清HIF-1α和GSK-3β水平,提高肾细胞耐缺氧的能力,从而发挥对重症急性胰腺炎肾损伤的保护作用。

Objective To study the effect of emodin on the levels of hypoxia inducible factor - 1 α （ HIF - 1 α） and glyco- gen synthase kinase -36 （GSK- 3β） in rats with severe acute pancreatitis （SAP）. Methods A total of 60 rats were randomly divided into blank group, sham - operation group, model group, control group and test group, each group had 12 rats. Model and test groups were injected with sodium taurocholate 0. 1 mL / 100 g to establish rat model of severe pancreatitis with renal injury. Sham -operation and control groups were gently flipped the duodenum and pancreas after opening the abdomen. Blank group was not given any treatment. Blank, sham - operation and model groups were given 5 μL · g^-1 0. 9% NaCl q6 h, intraperitoneal injection. Control and test groups were given 5 g · L^-1 emodin with the dose was 25 μg · g^ -1 q6 h, intraperitoneal injection. The serum creatinine （SCr）, urea nitrogen （ BUN）, HIF - 1 ot and GSK - 313 were compared between the five groups after operation 3, 6 and 12 h. Results The pancreatic histopathology score in model group was （9. 84 ± 1.05 ） points, which in blank, sham - operation, control and test groups were （1.30 ±0. 14）, （1.39 ± 0. 14）, （1.40 ± 0. 15 ）, （2. 73 ± 0. 30）points, the differences were significant （P 〈 0. 05 ）, and there were significant difference between test group and blank, sham - operation, control groups （P 〈 0. 05 ）. After operation 3 h, the main indexes in blank, sham - operation, control, model, test groups were compared, SCr were （60. 46 ±6. 78）, （61.52 ±6. 78）, （60. 38 ±6. 74）, （120. 57 ± 13.43）, （95.35 ±9.85） p.mol· L^-1; BUN were（7.47 ±0.79）, （8.02 ±0.92）, （7..93 ±0.83）, （12.49 ±1.53）, （8.56 ±0.89） mmol· L^-1; HIF-1α were （225.46 ±23.57）, （210.57 ±23.58）, （229.67 ±6.74）, （160.46 ±17.47）, （144.57 ±14. 85） μg · L^-1; GSK -3β were （6. 59 ±0.69）, （6.57 ±0.69）, （6.74 ±0.68）, （19.95 ±2. 13）, （10. 56 ± 1.39） μg · L^-1. After operation 6 h, the main indexes in blank, sham - operation, control, model, test groups were compared, SCr were （60.57 ±6.79）, （60.55 ±6.76）, （59.50 ±6.76）, （143.57 ± 15.47）, （110.57±12.55） μg · L^-1; BUN were （7.65 ±0.84）, （8.11 ±0.93）, （8.29 ±0.92）, （15.46 ±1.64）, （12.35 ± 1.37）mmol · L^-1; HIF - lot were （226.46 ±24.04）, （222.46 ±23.57）, （230.57 ±24.05）, （155.36±15.74）, （127.57±12.84）txg. L-1; GSK-313were（6.25±0.67）, （6.71±0.69）, （6.82±0.71）, （25.34 ±2. 64）, （ 11.56 ± 1.27） μg · L^-1 After operation 12 h, the main indexes in blank, sham - operation, control, model, test groups were compared, SCr were （60.61 ± 6.79）, （61.68 ± 6.79）, （61.54 ± 6.78）, （166.45±17.05）, （131.45 ±13.46） μg · L^-1 ; BUN were （8.03 ±0.85）, （7.98 ±0.82）, （8.79 ±0.93）, （18.66 ± 19.46） （15.35 ± 1.63） mmol · L^-1 , ; HIF - 1αt were （219.57 ± 23.63）, （226.35 ± 24. 04）, （220. 25 ±24. 04）, （ 148.46 ± 18.94 ）, （ 117.46 ± 12. 04 ） μg · L^-1 ; GSK - 3β were （ 6. 77 ± 0. 69 ）, （6.70±0.70）, （6.86±0.70）, （35.02±3.76）, （20.35 ±2.13）μg · L^-1 . After operation 3, 6 and 12 h, the SCr, BUN, HIF- 1α and GSK- 3β in blank, shamoperation and control groups were significantly different with those of model group （P 〈 0. 05 ） , and those indexes were significantly different between test and model groups after operation 3, 6 and 12 h （ P 〈 0. 05 ）. Conclusion Emodin may enhance the ability of renal ceils to hypoxia by increasing the level of serum HIF - 1α and GSK - 3 β, thus playing a protective role in rats of severe acute pancreatitis with renal injury.