Effects of Curcumin on Expression of iNOS and Investigation The Protective Effects on Rats with Severe Acute Panceratitis Associated Renal Injury_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 LIZhi-ling ^1,2 , ZHANGDong ¹ ,  LIUJiang-wei ¹ , WANGHao ¹ , LIRui ¹ , LIJian-ying ¹

1. The Key Laboratrary of The Special Environment of Xinjiang, Experimental Animal Institute, Urumuqi General Hospital of Lanzhou Military Region, Urumuqi 830000, Xinjiang Uygur Autonomous Region, China;
2. General Surgery, Second People's Hospital of Liangshan Prefecture, Xichang 615000, Sichuan Province, China;

Corresponding author：

LIUJiang-wei, Email: ljw273@sohu.com

Keywords：

Severe acute pancreatitis; Renal injury; Curcumin; Inducible nitric oxide synthase; Rat

DOI：

10.7507/1007-9424.20150110

Video：

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Objective To investigate the effects of curcumin on expression of iNOS mRNA, study the protective and therapeutic effects on rats with severe acute panceratitis associated renal injury, and explore the possible mechanisms. Methods A total of 24 rats were randomly divided into control group (n=8), severe acute panceratitis with renal injury group (injury group, n=8), and curcumin-treated group (treated group, n=8).The rats of control group and injury group were given 1.5 mL saline through intragastric administration at 3 h before operation, while the rats of treated group were fed with same amount of curcumin diluent at 3 h before operation.The rats of injury group and treated group with pancreatic head clamping method to establish the model of severe acute pancreatitis.At 12 h after modeling, rats in control group and injury group were perfused with 1.5 mL saline, and rats in treated group were intragastrically administrated to the same volume of curcumin diluent.All the rats were sacrificed at 18 h after modeling.The levels of serum amylase, creatinine, and blood urea nitrogen were detected and pathological chang of pancreas and the left kidney were observed under light microscope.The renal cell apoptosis were analyzed using TUNEL staining in three groups.The serum levels of interleukin-1β(IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) in three groups were detected by enzyme-linked immunosorbert assay (ELISA).The expressions of inducible nitric oxide synthase (iNOS) mRNA in the right kidney were detected with realtime polymerase chain reaction (RT-PCR) in three groups. Results Compared with the control group, the levels of serum amylase, creatinine, blood urea nitrogen, IL-1β, IL-6, and IL-10, the cell apoptosis and the expressions of iNOS mRNA in injury group and treated group were significantly increased (P < 0.05).In the treated group, the level of IL-10 was higher than the injury group (P < 0.05), and the difference of other indexes were lower than the injury group (P < 0.05). Conclusions Curcumin has a better protective effect on severe acute pancreatitis associated renal injury.It may be through inhibited the expressions of IL-1βand IL-6, stimulated the expression of IL-10, and down-regulation of iNOS mRNA expression to reduce the generation of oxygen free radicals and NO damage to cell and reducing the cell apoptosis and necrosis of kidney.

Citation： LIZhi-ling, ZHANGDong, LIUJiang-wei, WANGHao, LIRui, LIJian-ying. Effects of Curcumin on Expression of iNOS and Investigation The Protective Effects on Rats with Severe Acute Panceratitis Associated Renal Injury. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(4): 412-417. doi: 10.7507/1007-9424.20150110 Copy

1.	Bennett M, Dent CL, Ma Q, et al.Urine NGAL predicts severity of acute kidney injury after cardiac surgery:a prospective study.Clin J Am Soc Nephrol, 2008, 3(3):665-673.
2.	龚小见, 陈华国, 赵超, 等.姜黄活性成分对血小板聚集及小鼠常压耐氧能力的影响.中国实验方剂学杂志, 2010, 16(11):125-127.
3.	Shen SQ, Zhang Y, Xiang JJ, et al.Protective effect of curcumin against liver warm ischemia/reperfusion injury in rat model is associated with regulation of heat shock protein and antioxidant enzymes.World J Gastroenterol, 2007, 13(13):1953-1961.
4.	Masuda T, Hidaka K, Shinohara A, et al.Chemical studies on antioxidant mechanism of curcuminoid:analysis of radical reaction products from curcumin.J Agric Food Chem, 1999, 47(1):72-77.
5.	曾繁余, 刘菁, 袁桂峰, 等.姜黄素对HepG-2细胞增殖与凋亡的影响.中国普通外科杂志, 2013, 22(4):474-478.
6.	俞婷婷, 蒋福升, 刘楠楠, 等.姜黄素衍生物体外释放及抗肿瘤作用研究.中国现代应用药学, 2013, 30(3):289-294.
7.	沃兴德, 洪行球, 高承贤, 等.姜黄素长期毒性试验.浙江中医学报, 2000, 24(1):61-65.
8.	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.中国急救医学, 2014, 34(3):251-254.
9.	刘垒, 王卫星, 余佳, 等.iNOS及eNOS mRNA表达在急性坏死性胰腺炎肺损伤中的作用.中国普外基础与临床杂志, 2010, 17(5):449-453.
10.	刘晓芹, 张九成.NO与缺血性脑卒中中患者颈动脉粥样硬化斑块的相关性分析.中国实用神经疾病杂志, 2014, 17(19):81-82.
11.	武永胜, 李得溪, 赵海平, 等.银杏叶提取物对重症急性胰腺炎大鼠脑组织中IL-1β、IL-6、和TNF-α表达水平的影响.中国普外基础与临床杂志, 2012, 19(6):616-621.
12.	王先坤, 詹乐恒, 王世文, 等.IL-10, IL-18在重症急性胰腺炎肺损伤中的作用.中国普外基础与临床杂志, 2005, 12(5):443-446.
13.	Förstermann U, Kleinert H.Nitric oxide synthase:expression and expressional control of the three isoforms.Naunyn Schmiedebergs Arch Pharmacol, 1995, 352(4):351-364.
14.	刘熹, 刘浩, 赵小丹, 等.聚乳酸补片阻隔纤维环穿刺后椎间盘内炎性反应的研究.中国修复重建外科杂志, 2010, 24(10):1159-1163.
15.	杨宝峰, 苏定冯, 周宏灏.药理学.第7版.北京:人民卫生出版社, 2008:310-311.
16.	Sun W, Wu J, Lin L, et al.Porphyromonas gingivalis stimulates the release of nitric oxide by inducing expression of inducible nitric oxide synthases and inhibiting endothelial nitric oxide synthases.J Periodontal Res, 2010, 45(3):381-388.
17.	Kozhukhar AV, Yasinska IM, Sumbayev VV.Nitric oxide inhibits HIF-1alpha protein accumulation under hypoxic conditions:implica-tion of 2-oxoglutarate and iron.Biochimie, 2006, 88(5):411-418.
18.	Liebertthal W.Biology of ischemic and toxic renal tubular cell injury:role of nitric oxide and the inflammatory response.Curr Opin Nephrol Hypertens, 1998, 7(3):289-295.
19.	Selvam R, Subramanian L, Gayathri R, et al.The anti-oxidangt acti-vity of turn eric (Curcuma longa).J Ethnopharol, 1995, 47(2):59-59.
20.	石晶, 顾军, 邓心新, 等.姜黄素对大鼠心肌缺血性损伤的保护作用.中国药理学通报, 1998, 14(2):145-145.
21.	Chen YR, Tan TH.Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway by curcumin.Oncogene, 1998, 17(2):173-178.
22.	Novovic S, Andersen AM, Ersboll AK, et al.Proinflammatory cytokines in alcohol or gallstone induced acute pancreatitis.A prospective study.JOP, 2009, 10(3):256-262.
23.	Morre KW, de Waal Malefty R, Coffman RT, et al.Inerleukin-10 and the inerleukin-10 receptor.Annu Rev Immunol, 2001, 19:683-765.
24.	李晓萍, 张志坚, 屈纪富.将黄书对大鼠重症胰腺炎的干预效应研究.第三军医大学学报, 2013, 35(8):759-763.
25.	刘静, 黄丽, 胡晓松, 等.姜黄素对大鼠重症急性胰腺炎防治作用及其机制.中国普通外科杂志, 2012, 21(3):283-289.

1. Bennett M, Dent CL, Ma Q, et al.Urine NGAL predicts severity of acute kidney injury after cardiac surgery:a prospective study.Clin J Am Soc Nephrol, 2008, 3(3):665-673.
2. 龚小见, 陈华国, 赵超, 等.姜黄活性成分对血小板聚集及小鼠常压耐氧能力的影响.中国实验方剂学杂志, 2010, 16(11):125-127.
3. Shen SQ, Zhang Y, Xiang JJ, et al.Protective effect of curcumin against liver warm ischemia/reperfusion injury in rat model is associated with regulation of heat shock protein and antioxidant enzymes.World J Gastroenterol, 2007, 13(13):1953-1961.
4. Masuda T, Hidaka K, Shinohara A, et al.Chemical studies on antioxidant mechanism of curcuminoid:analysis of radical reaction products from curcumin.J Agric Food Chem, 1999, 47(1):72-77.
5. 曾繁余, 刘菁, 袁桂峰, 等.姜黄素对HepG-2细胞增殖与凋亡的影响.中国普通外科杂志, 2013, 22(4):474-478.
6. 俞婷婷, 蒋福升, 刘楠楠, 等.姜黄素衍生物体外释放及抗肿瘤作用研究.中国现代应用药学, 2013, 30(3):289-294.
7. 沃兴德, 洪行球, 高承贤, 等.姜黄素长期毒性试验.浙江中医学报, 2000, 24(1):61-65.
8. 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.中国急救医学, 2014, 34(3):251-254.
9. 刘垒, 王卫星, 余佳, 等.iNOS及eNOS mRNA表达在急性坏死性胰腺炎肺损伤中的作用.中国普外基础与临床杂志, 2010, 17(5):449-453.
10. 刘晓芹, 张九成.NO与缺血性脑卒中中患者颈动脉粥样硬化斑块的相关性分析.中国实用神经疾病杂志, 2014, 17(19):81-82.
11. 武永胜, 李得溪, 赵海平, 等.银杏叶提取物对重症急性胰腺炎大鼠脑组织中IL-1β、IL-6、和TNF-α表达水平的影响.中国普外基础与临床杂志, 2012, 19(6):616-621.
12. 王先坤, 詹乐恒, 王世文, 等.IL-10, IL-18在重症急性胰腺炎肺损伤中的作用.中国普外基础与临床杂志, 2005, 12(5):443-446.
13. Förstermann U, Kleinert H.Nitric oxide synthase:expression and expressional control of the three isoforms.Naunyn Schmiedebergs Arch Pharmacol, 1995, 352(4):351-364.
14. 刘熹, 刘浩, 赵小丹, 等.聚乳酸补片阻隔纤维环穿刺后椎间盘内炎性反应的研究.中国修复重建外科杂志, 2010, 24(10):1159-1163.
15. 杨宝峰, 苏定冯, 周宏灏.药理学.第7版.北京:人民卫生出版社, 2008:310-311.
16. Sun W, Wu J, Lin L, et al.Porphyromonas gingivalis stimulates the release of nitric oxide by inducing expression of inducible nitric oxide synthases and inhibiting endothelial nitric oxide synthases.J Periodontal Res, 2010, 45(3):381-388.
17. Kozhukhar AV, Yasinska IM, Sumbayev VV.Nitric oxide inhibits HIF-1alpha protein accumulation under hypoxic conditions:implica-tion of 2-oxoglutarate and iron.Biochimie, 2006, 88(5):411-418.
18. Liebertthal W.Biology of ischemic and toxic renal tubular cell injury:role of nitric oxide and the inflammatory response.Curr Opin Nephrol Hypertens, 1998, 7(3):289-295.
19. Selvam R, Subramanian L, Gayathri R, et al.The anti-oxidangt acti-vity of turn eric (Curcuma longa).J Ethnopharol, 1995, 47(2):59-59.
20. 石晶, 顾军, 邓心新, 等.姜黄素对大鼠心肌缺血性损伤的保护作用.中国药理学通报, 1998, 14(2):145-145.
21. Chen YR, Tan TH.Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway by curcumin.Oncogene, 1998, 17(2):173-178.
22. Novovic S, Andersen AM, Ersboll AK, et al.Proinflammatory cytokines in alcohol or gallstone induced acute pancreatitis.A prospective study.JOP, 2009, 10(3):256-262.
23. Morre KW, de Waal Malefty R, Coffman RT, et al.Inerleukin-10 and the inerleukin-10 receptor.Annu Rev Immunol, 2001, 19:683-765.
24. 李晓萍, 张志坚, 屈纪富.将黄书对大鼠重症胰腺炎的干预效应研究.第三军医大学学报, 2013, 35(8):759-763.
25. 刘静, 黄丽, 胡晓松, 等.姜黄素对大鼠重症急性胰腺炎防治作用及其机制.中国普通外科杂志, 2012, 21(3):283-289.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effects of Curcumin on Expression of iNOS and Investigation The Protective Effects on Rats with Severe Acute Panceratitis Associated Renal Injury

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