Effects of Emodin on the Expression of Hypoxia Inducible Factor-1α Protein in Rats with Severe Acute Pancreatitis-associated Renal Injury_West China Medical Journal

Authors：

 LIZhi-ling ^1,2 , 张东 ² ,  ZHANGDong ² , LIUJiang-wei ²

1. Department of General Surgery, the Second People's Hospital of Liangshan Prefecture, Xichang, Sichuan 615000, P. R. China;
2. Department of Hepatobiliary Surgery, Urumuqi General Hospital of Lanzhou Military Region, Urumuqi, Xinjiang 830000, P. R. China;

Corresponding author：

ZHANGDong, Email: ljw273@sohu.com

Keywords：

Severe acute pancreatitis; Renal injury; Emodin; Hypoxia inducible factor-1α; Rats

DOI：

10.7507/1002-0179.20150186

Video：

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Objective To investigate the effect of emodin on the expression of hypoxia inducible factor (HIF)-1α protein in rats with severe acute pancreatitis-associated renal injury and explore the possible mechanisms. Methods A total of 72 rats were randomly divided into sham-operated group (n=24), severe acute pancreatitis with renal injury group (injury group, n=24), and treatment group (n=24). The sham-operated and injury groups were given 1.5 mL saline through intragastric administration before operation while the treatment group was fed with the same amount of 50 mg/kg emodin diluent. The pancreas and pancreatic tail-segment was dissociated and the head of pancreas was occluded in rats to form the model, and blood vessel forceps were loosed after three hours. All the rats were sacrificed 12, 24 and 36 hours after modeling. The level of ascites, serum amylase, creatinine, blood urea nitrogen were detected. Hematoxylin-eosin staining was used to observe the pancreatic and renal pathological changes, and immunohistochemical method was used to detect the expression of HIF-1α protein level in the kidney. Results Compared with the sham-operated group, the level of ascites, serum amylase, creatinine, blood urea nitrogen and the expression of HIF-1α protein level increased significantly. The tissue damage of pancreas and the kidney became more serious. Compared with the injury group, the kidney and pancreas function of the treatment group had a better performance. HIF-1α protein level significantly increased in the treatment group, and the difference had a statistical significance (P<0.05). Conclusion Emodin has a good protective effect on severe acute pancreatitis-associated renal injury. It may function through up-regulation expression of HIF-1α protein level to improve the ability of the kidney to tolerate hypoxia, and then reduce the cell apoptosis and necrosis of the kidney.

Citation： LIZhi-ling, ZHANGDong, LIUJiang-wei. Effects of Emodin on the Expression of Hypoxia Inducible Factor-1α Protein in Rats with Severe Acute Pancreatitis-associated Renal Injury. West China Medical Journal, 2015, 30(4): 640-644. doi: 10.7507/1002-0179.20150186 Copy

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1. 陈宗平, 梁国标, 杨亦彬, 等. HIF-1α在肾缺血-再灌注损伤及高压氧、丹参酮ⅡA治疗中的表达及意义[J]. 中国医院药学杂志, 2012, 32(4):246-251.
2. 谢智慧, 陈宗平, 曹瑞, 等. 高压氧干预对大鼠肾缺血再灌注肾组织低氧诱导因子-1αmRNA表达的影响[J]. 中华物理医学与康复杂志, 2010, 32(3):182-185.
3. Mooring SR, Wang BH. HIH-1 inhibitors as anti-cancer therapy[J]. Sci China Chem, 2011, 54(1):24-30.
4. Hazni H, Ahmad N, Hitotsuyanagi Y, et al. Phytochemical constituents from cassia alata with inhibition against methicillin-resistant Staphylococcus aureus (MRSA)[J]. Planta Med, 2008, 74(15):1802-1805.
5. 童洪飞, 林胜璋, 杨潇, 等. 大黄素抗大鼠肝移植急性排斥反应的实验研究[J]. 中华中医药杂志, 2009, 24(1):49-52.
6. 陈廷芳, 陈明, 秦建华, 等. 转化生长因子β1/整合素连接激酶信号通路在大鼠肾小管上皮细胞转分化中的作用及大黄素对其的干预效应[J]. 中西医结合学报, 2009, 7(1):59-64.
7. 李之令, 张东, 刘江伟, 等. 胰头夹闭法致大鼠重症急性胰腺炎相关性肾损伤动物模型的建立[J]. 中国急救医学, 2014, 34(3):251-254, 后插1.
8. Holmquist-Mengelbier L, Fredlund E, Löfstedt T, et al. Recruitment of HIF-1alpha and HIF-2alpha to common target genes is differentially regulated in neuroblastoma:HIF-2alpha promotes an aggressive phenotype[J]. Cancer Cell, 2006, 10(5):413-423.
9. Song YR, You SJ, Lee YM, et al. Activation of hypoxia-inducible factor attenuates renal injury in rat remnant kidney[J]. Nephrol Dial Transplant, 2010, 25(1):77-85.
10. Schofield CJ, Ratcliffe PJ. Signalling hypoxia by HIF hydroxylases[J]. Biochem Biophys Res Commun, 2005, 338(1):617-626.
11. Haase VH. Hypoxia-inducible factors in the kidney[J]. Am J Physiol Renal Physiol, 2006, 291(2):F271-F281.
12. Weidemann A, Bernhardt WM, Klanke B, et al. HIF activation protects from acute kidney injury[J]. J Am Soc Nephrol, 2008, 19(3):486-494.
13. Nangaku M, Nishi H, Miyata T. Role of chronic hypoxia and hypoxia inducible factor in kidney disease[J]. Chin Med J (Engl), 2008, 121(3):257-264.
14. 霍文谦, 靳风烁, 李黔生, 等. 肾小管缺氧损伤中肾损伤分子-1表达信号通路的调节[J]. 肾脏病与透析肾移植杂志, 2011, 20(1):34-39.
15. Mayer G. Capillary rarefaction, hypoxia, VEGF and angiogenesis in chronic renal disease[J]. Nephrol Dial Transplant, 2011, 26(4):1132-1137.
16. Crosby ME, Devlin CM, Glazer PM, et al. Emerging roles of microRNAs in the molecular responses to hypoxia[J]. Curr Pharm Des, 2009, 15(33):3861-3866.
17. 李贺, 汪泱, 刘芬, 等. 肾缺血再灌注损伤后缺氧诱导因子-1αL及其靶基因miR-210、血管内皮生长因子的动态表达[J]. 中华实验外科杂志, 2011, 28(12):2074-2076.
18. 王苹苹, 孔繁平, 陈学群. 低氧细胞应激的HIF-1信号通路[J]. 浙江大学学报:医学版, 2011, 40(5):559-566.
19. Simon MC. Coming up for air:HIF-1 and mitochondrial oxygen consumption[J]. Cell Metab, 2006, 3(3):150-151.
20. Zhao F, Mancuso A, Bui TV, et al. Imatinib resistance associated with BCR-ABL upregulation is dependent on HIF-1alpha-induced metabolic reprograming[J]. Oncogene, 2010, 29(20):2962-2972.
21. 钟强, 黄忠. 重症急性胰腺炎并发多器官功能障碍及预后关系的临床研究[J]. 华西医学, 2012, 27(4):54-56.
22. 苗戎, 陈静, 朱婕, 等. 大黄对体外内毒素诱生的肺泡巨噬细胞分秘功能的影响[J]. 中草药, 1998, 29(6):395.
23. 李敏, 李丽霞, 刘渝, 等. 大黄研究进展[J]. 世界科学技术, 2006, 8(4):34-39.

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Effects of Emodin on the Expression of Hypoxia Inducible Factor-1α Protein in Rats with Severe Acute Pancreatitis-associated Renal Injury

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