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.	龔小見, 陳華國, 趙超, 等.姜黃活性成分對血小板聚集及小鼠常壓耐氧能力的影響.中國實驗方劑學雜志, 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, 劉菁, 袁桂峰, 等.姜黃素對HepG-2細胞增殖與凋亡的影響.中國普通外科雜志, 2013, 22(4):474-478.
6.	俞婷婷, 蔣福升, 劉楠楠, 等.姜黃素衍生物體外釋放及抗腫瘤作用研究.中國現代應用藥學, 2013, 30(3):289-294.
7.	沃興德, 洪行球, 高承賢, 等.姜黃素長期毒性試驗.浙江中醫學報, 2000, 24(1):61-65.
8.	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.中國急救醫學, 2014, 34(3):251-254.
9.	劉壘, 王衛星, 余佳, 等.iNOS及eNOS mRNA表達在急性壞死性胰腺炎肺損傷中的作用.中國普外基礎與臨床雜志, 2010, 17(5):449-453.
10.	劉曉芹, 張九成.NO與缺血性腦卒中中患者頸動脈粥樣硬化斑塊的相關性分析.中國實用神經疾病雜志, 2014, 17(19):81-82.
11.	武永勝, 李得溪, 趙海平, 等.銀杏葉提取物對重癥急性胰腺炎大鼠腦組織中IL-1β、IL-6、和TNF-α表達水平的影響.中國普外基礎與臨床雜志, 2012, 19(6):616-621.
12.	王先坤, 詹樂恒, 王世文, 等.IL-10, IL-18在重癥急性胰腺炎肺損傷中的作用.中國普外基礎與臨床雜志, 2005, 12(5):443-446.
13.	F?rstermann U, Kleinert H.Nitric oxide synthase:expression and expressional control of the three isoforms.Naunyn Schmiedebergs Arch Pharmacol, 1995, 352(4):351-364.
14.	劉熹, 劉浩, 趙小丹, 等.聚乳酸補片阻隔纖維環穿刺后椎間盤內炎性反應的研究.中國修復重建外科雜志, 2010, 24(10):1159-1163.
15.	楊寶峰, 蘇定馮, 周宏灝.藥理學.第7版.北京:人民衛生出版社, 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, 顧軍, 鄧心新, 等.姜黃素對大鼠心肌缺血性損傷的保護作用.中國藥理學通報, 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.	李曉萍, 張志堅, 屈紀富.將黃書對大鼠重癥胰腺炎的干預效應研究.第三軍醫大學學報, 2013, 35(8):759-763.
25.	劉靜, 黃麗, 胡曉松, 等.姜黃素對大鼠重癥急性胰腺炎防治作用及其機制.中國普通外科雜志, 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. 龔小見, 陳華國, 趙超, 等.姜黃活性成分對血小板聚集及小鼠常壓耐氧能力的影響.中國實驗方劑學雜志, 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, 劉菁, 袁桂峰, 等.姜黃素對HepG-2細胞增殖與凋亡的影響.中國普通外科雜志, 2013, 22(4):474-478.
6. 俞婷婷, 蔣福升, 劉楠楠, 等.姜黃素衍生物體外釋放及抗腫瘤作用研究.中國現代應用藥學, 2013, 30(3):289-294.
7. 沃興德, 洪行球, 高承賢, 等.姜黃素長期毒性試驗.浙江中醫學報, 2000, 24(1):61-65.
8. 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.中國急救醫學, 2014, 34(3):251-254.
9. 劉壘, 王衛星, 余佳, 等.iNOS及eNOS mRNA表達在急性壞死性胰腺炎肺損傷中的作用.中國普外基礎與臨床雜志, 2010, 17(5):449-453.
10. 劉曉芹, 張九成.NO與缺血性腦卒中中患者頸動脈粥樣硬化斑塊的相關性分析.中國實用神經疾病雜志, 2014, 17(19):81-82.
11. 武永勝, 李得溪, 趙海平, 等.銀杏葉提取物對重癥急性胰腺炎大鼠腦組織中IL-1β、IL-6、和TNF-α表達水平的影響.中國普外基礎與臨床雜志, 2012, 19(6):616-621.
12. 王先坤, 詹樂恒, 王世文, 等.IL-10, IL-18在重癥急性胰腺炎肺損傷中的作用.中國普外基礎與臨床雜志, 2005, 12(5):443-446.
13. F?rstermann U, Kleinert H.Nitric oxide synthase:expression and expressional control of the three isoforms.Naunyn Schmiedebergs Arch Pharmacol, 1995, 352(4):351-364.
14. 劉熹, 劉浩, 趙小丹, 等.聚乳酸補片阻隔纖維環穿刺后椎間盤內炎性反應的研究.中國修復重建外科雜志, 2010, 24(10):1159-1163.
15. 楊寶峰, 蘇定馮, 周宏灝.藥理學.第7版.北京:人民衛生出版社, 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, 顧軍, 鄧心新, 等.姜黃素對大鼠心肌缺血性損傷的保護作用.中國藥理學通報, 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. 李曉萍, 張志堅, 屈紀富.將黃書對大鼠重癥胰腺炎的干預效應研究.第三軍醫大學學報, 2013, 35(8):759-763.
25. 劉靜, 黃麗, 胡曉松, 等.姜黃素對大鼠重癥急性胰腺炎防治作用及其機制.中國普通外科雜志, 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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