Protective Mechanism of Resveratrol on Kidney Injury of Obstructive Jaundice in Rat_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 MIAOZhi-zhao ,  WUShan-min , CHENChen , XUChao-long

Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China;

Corresponding author：

WUShan-min, Email: 15327278328@163.com

Keywords：

Resveratrol; Obstructive jaundice; Kidney; Silent information regulator 1; Nuclear factor-κB

DOI：

10.7507/1007-9424.20150047

Video：

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Objective To explore the protective mechanism and effect of the resveratrol for kidney injury of obstructive jaundice. Methods The rats were randomly divided into three groups: sham operation group receiving laparotomy without bile duct ligation (BDL), the obstructive jaundice group with BDL, and the obstructive jaundice + resveratrol group given resveratrol following BDL. The levels of total bilirubin (TBIL), direct bilirubin (DBIL), blood urea nitrogen (BUN), and creatinine (Cr) in the serum were tested. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, glutathione (GSH) level in the renal tissues were detected. The expressions of the silent information regulator 1 (SIRT1) and nuclear factor-κB (NF-κB) proteins were tested by Western blot. The expression of SIRT1 mRNA was detected by RT-PCR and the renal cell apoptosis was examined by TUNEL staining. Results ①Compared with the sham operation group, the levels of serum TBIL, DBIL, BUN and Cr were significantly higher (P < 0.05); the activity of SOD and level of GSH, and the expressions of SIRT1 mRNA and SIRT1 protein in the renal tissues were signi-ficantly lower (P < 0.05); the content of MDA, the expression of NF-κB protein, and the rate of cell apoptosis in the renal tissues were significantly higher (P < 0.05) in the obstructive jaundice group.②Compared with the obstructive jaundice group, the levels of serum TBIL, DBIL, BUN and Cr were significantly lower (P < 0.05); the activity of SOD and level of GSH, and the expressions of SIRT1 mRNA and SIRT1 protein in the renal tissues were significantly higher (P < 0.05); the content of MDA, the expression of NF-κB protein, and the rate of cell apoptosis in the renal tissues were significantly lower (P < 0.05) in the obstructive jaundice+resveratrol group. Conclusion The resveratrol could alleviate renal damage and play a beneficial role to resist inflammation, oxidation, and apoptosis by activating the SIRT1 which probably inhibits the expression of NF-κB protein and promotes the activity of SOD in cholestatic kidney injury.

Citation： MIAOZhi-zhao, WUShan-min, CHENChen, XUChao-long. Protective Mechanism of Resveratrol on Kidney Injury of Obstructive Jaundice in Rat. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(2): 172-175. doi: 10.7507/1007-9424.20150047 Copy

1.	Cai YJ, Wei QY, Fang JG, et al. The 3, 4-dihydroxyl groups are impor-tant for trans-resveratrol analogs to exhibit enhanced antioxidant and apoptotic activities. Anticancer Res, 2004, 24(2B): 999-1002.
2.	Leiro J, Alvarez E, Arranz JA, et al. Effects of cis-resveratrol on infla-mmatory murine macrophages: antioxidant activity and down-regu-lation of inflammatory genes. J Leukoc Biol, 2004, 75(6): 1156-1165.
3.	Lin TK, Huang LT, Huang YH, et al. The effect of the red wine poly-phenol resveratrol on a rat model of biliary obstructed cholestasis: involvement of anti-apoptotic signalling, mitochondrial biogenesis and the induction of autophagy. Apoptosis, 2012, 17(8): 871-879.
4.	Ara C, Karabulut AB, Kirimlioglu H, et al. Protective effect of resveratrol against renal oxidative stress in cholestasis. Ren Fail, 2005, 27(4): 435-440.
5.	张丰深, 何振平, 段恒春, 等.阻塞性黄疸大鼠肾脏自分泌内皮素的变化及其与肾功能损害的关系.中国普外基础与临床杂志, 2003, 10(1): 22-24.
6.	Stähelin BJ, Marti U, Zimmermann H, et al. The interaction of Bcl-2 and Bax regulates apoptosis in biliary epithelial cells of rats with obstructive jaundice. Virchows Arch, 1999, 434(4): 333-339.
7.	彭兵, 吴言涛, 王向东, 等.阻塞性黄疸患者手术前后内毒素、内皮素及细胞因子水平的研究.中国普外基础与临床杂志, 2001, 8(4): 245-246.
8.	Green J, Better OS. Systemic hypotension and renal failure in obstructive jaundice-mechanistic and therapeutic aspects. J Am Soc Nephrol, 1995, 5(11): 1853-1871.
9.	Chen D, Steele AD, Lindquist S, et al. Increase in activity during calorie restriction requires Sirt1. Science, 2005, 310(5754): 1641.
10.	Cohen HY, Miller C, Bitterman KJ, et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science, 2004, 305(5682): 390-392.
11.	Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol. J Biol Chem, 2005, 280(17): 17187-17195.
12.	Yeung F, Hoberg JE, Ramsey CS, et al. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J, 2004, 23(12): 2369-2380.
13.	Tanno M, Kuno A, Yano T, et al. Induction of manganese superoxide dismutase by nuclear translocation and activation of SIRT1 promotes cell survival in chronic heart failure. J Biol Chem, 2010, 285(11): 8375-8382.

1. Cai YJ, Wei QY, Fang JG, et al. The 3, 4-dihydroxyl groups are impor-tant for trans-resveratrol analogs to exhibit enhanced antioxidant and apoptotic activities. Anticancer Res, 2004, 24(2B): 999-1002.
2. Leiro J, Alvarez E, Arranz JA, et al. Effects of cis-resveratrol on infla-mmatory murine macrophages: antioxidant activity and down-regu-lation of inflammatory genes. J Leukoc Biol, 2004, 75(6): 1156-1165.
3. Lin TK, Huang LT, Huang YH, et al. The effect of the red wine poly-phenol resveratrol on a rat model of biliary obstructed cholestasis: involvement of anti-apoptotic signalling, mitochondrial biogenesis and the induction of autophagy. Apoptosis, 2012, 17(8): 871-879.
4. Ara C, Karabulut AB, Kirimlioglu H, et al. Protective effect of resveratrol against renal oxidative stress in cholestasis. Ren Fail, 2005, 27(4): 435-440.
5. 张丰深, 何振平, 段恒春, 等.阻塞性黄疸大鼠肾脏自分泌内皮素的变化及其与肾功能损害的关系.中国普外基础与临床杂志, 2003, 10(1): 22-24.
6. Stähelin BJ, Marti U, Zimmermann H, et al. The interaction of Bcl-2 and Bax regulates apoptosis in biliary epithelial cells of rats with obstructive jaundice. Virchows Arch, 1999, 434(4): 333-339.
7. 彭兵, 吴言涛, 王向东, 等.阻塞性黄疸患者手术前后内毒素、内皮素及细胞因子水平的研究.中国普外基础与临床杂志, 2001, 8(4): 245-246.
8. Green J, Better OS. Systemic hypotension and renal failure in obstructive jaundice-mechanistic and therapeutic aspects. J Am Soc Nephrol, 1995, 5(11): 1853-1871.
9. Chen D, Steele AD, Lindquist S, et al. Increase in activity during calorie restriction requires Sirt1. Science, 2005, 310(5754): 1641.
10. Cohen HY, Miller C, Bitterman KJ, et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science, 2004, 305(5682): 390-392.
11. Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol. J Biol Chem, 2005, 280(17): 17187-17195.
12. Yeung F, Hoberg JE, Ramsey CS, et al. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J, 2004, 23(12): 2369-2380.
13. Tanno M, Kuno A, Yano T, et al. Induction of manganese superoxide dismutase by nuclear translocation and activation of SIRT1 promotes cell survival in chronic heart failure. J Biol Chem, 2010, 285(11): 8375-8382.

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Protective Mechanism of Resveratrol on Kidney Injury of Obstructive Jaundice in Rat

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