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 , 張東 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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5.	童洪飛, 林勝璋, 楊瀟, 等. 大黃素抗大鼠肝移植急性排斥反應的實驗研究[J]. 中華中醫藥雜志, 2009, 24(1):49-52.
6.	陳廷芳, 陳明, 秦建華, 等. 轉化生長因子β1/整合素連接激酶信號通路在大鼠腎小管上皮細胞轉分化中的作用及大黃素對其的干預效應[J]. 中西醫結合學報, 2009, 7(1):59-64.
7.	李之令, 張東, 劉江偉, 等. 胰頭夾閉法致大鼠重癥急性胰腺炎相關性腎損傷動物模型的建立[J]. 中國急救醫學, 2014, 34(3):251-254, 后插1.
8.	Holmquist-Mengelbier L, Fredlund E, L?fstedt 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.	霍文謙, 靳風爍, 李黔生, 等. 腎小管缺氧損傷中腎損傷分子-1表達信號通路的調節[J]. 腎臟病與透析腎移植雜志, 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.
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17.	李賀, 汪泱, 劉芬, 等. 腎缺血再灌注損傷后缺氧誘導因子-1αL及其靶基因miR-210、血管內皮生長因子的動態表達[J]. 中華實驗外科雜志, 2011, 28(12):2074-2076.
18.	王蘋蘋, 孔繁平, 陳學群. 低氧細胞應激的HIF-1信號通路[J]. 浙江大學學報:醫學版, 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.	鐘強, 黃忠. 重癥急性胰腺炎并發多器官功能障礙及預后關系的臨床研究[J]. 華西醫學, 2012, 27(4):54-56.
22.	苗戎, 陳靜, 朱婕, 等. 大黃對體外內毒素誘生的肺泡巨噬細胞分秘功能的影響[J]. 中草藥, 1998, 29(6):395.
23.	李敏, 李麗霞, 劉渝, 等. 大黃研究進展[J]. 世界科學技術, 2006, 8(4):34-39.

1. 陳宗平, 梁國標, 楊亦彬, 等. HIF-1α在腎缺血-再灌注損傷及高壓氧、丹參酮ⅡA治療中的表達及意義[J]. 中國醫院藥學雜志, 2012, 32(4):246-251.
2. 謝智慧, 陳宗平, 曹瑞, 等. 高壓氧干預對大鼠腎缺血再灌注腎組織低氧誘導因子-1αmRNA表達的影響[J]. 中華物理醫學與康復雜志, 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. 童洪飛, 林勝璋, 楊瀟, 等. 大黃素抗大鼠肝移植急性排斥反應的實驗研究[J]. 中華中醫藥雜志, 2009, 24(1):49-52.
6. 陳廷芳, 陳明, 秦建華, 等. 轉化生長因子β1/整合素連接激酶信號通路在大鼠腎小管上皮細胞轉分化中的作用及大黃素對其的干預效應[J]. 中西醫結合學報, 2009, 7(1):59-64.
7. 李之令, 張東, 劉江偉, 等. 胰頭夾閉法致大鼠重癥急性胰腺炎相關性腎損傷動物模型的建立[J]. 中國急救醫學, 2014, 34(3):251-254, 后插1.
8. Holmquist-Mengelbier L, Fredlund E, L?fstedt 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. 霍文謙, 靳風爍, 李黔生, 等. 腎小管缺氧損傷中腎損傷分子-1表達信號通路的調節[J]. 腎臟病與透析腎移植雜志, 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. 李賀, 汪泱, 劉芬, 等. 腎缺血再灌注損傷后缺氧誘導因子-1αL及其靶基因miR-210、血管內皮生長因子的動態表達[J]. 中華實驗外科雜志, 2011, 28(12):2074-2076.
18. 王蘋蘋, 孔繁平, 陳學群. 低氧細胞應激的HIF-1信號通路[J]. 浙江大學學報:醫學版, 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. 鐘強, 黃忠. 重癥急性胰腺炎并發多器官功能障礙及預后關系的臨床研究[J]. 華西醫學, 2012, 27(4):54-56.
22. 苗戎, 陳靜, 朱婕, 等. 大黃對體外內毒素誘生的肺泡巨噬細胞分秘功能的影響[J]. 中草藥, 1998, 29(6):395.
23. 李敏, 李麗霞, 劉渝, 等. 大黃研究進展[J]. 世界科學技術, 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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