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山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (9): 41-46.doi: 10.6040/j.issn.1671-7554.0.2014.716

• 基础医学 • 上一篇    下一篇

葡萄籽原花青素对小鼠脂肪肝模型缺血再灌注造成的急性肝损伤的保护作用

李少伟1,2,3, 刘宗正1,2, 刘春霞1,2, 张焱如1,2, 周欢敏1,2   

  1. 1. 内蒙古农业大学生命科学学院, 内蒙古 呼和浩特 010018;
    2. 内蒙古自治区生物制造重点实验室, 内蒙古 呼和浩特 010018;
    3. 内蒙古医科大学基础医学院分子生物学研究中心, 内蒙古 呼和浩特, 010059
  • 收稿日期:2014-10-16 出版日期:2015-09-10 发布日期:2015-09-10
  • 通讯作者: 周欢敏。E-mail:huanminzhou@263.net E-mail:huanminzhou@263.net
  • 基金资助:
    内蒙古自然科学基金重大项目(2010ZD10)

Protective effect of grape seed proanthocyanidins in mouse fatty liver models suffering ischemia-reperfusion injury

LI Shaowei1,2,3, LIU Zongzheng1,2, LIU Chunxia1,2, ZHANG Yanru1,2, ZHOU Huanmin1,2   

  1. 1. College of Life Sciences, Inner Mongolia Agricultural University, Hohhot 010018, Inner Mongolia, China;
    2. Inner Mongolia Key Laboratory of Biomanufacture, Hohhot 010018, Inner Mongolia, China;
    3. Center of Molecular Biology, Basic Medical College, Inner Mongolia Medical University, Hohhot 010059, Inner Mongolia, China
  • Received:2014-10-16 Online:2015-09-10 Published:2015-09-10
  • Contact: 周欢敏。E-mail:huanminzhou@263.net E-mail:huanminzhou@263.net

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摘要： 目的 探讨葡萄籽原花青素对脂肪肝缺血再灌注(IR)损伤小鼠模型的保护作用。方法 将30只C57BL/6小鼠随机分为3组。喂食蛋氨酸胆碱缺乏高脂饲料3周后进行非酒精性脂肪肝造模,实验分3组:假手术组、对照组(肝脏缺血再灌注前灌服蒸馏水)、花青素缺血再灌注组(肝脏缺血再灌注前灌服原花青素)。再灌注6 h后处死小鼠,检测血清中丙氨酸转氨酶(AST)和天冬氨酸转氨酶(ALT)含量,观察肝脏组织形态学变化,分析肝脏组织损伤程度,巨噬细胞浸润程度,炎性因子TNF-α、IL-6、iNOS、INFγmRNA表达水平和肝脏组织内p38蛋白表达水平。结果 与对照组相比较,花青素组血清ALT和AST水平较低(P<0.05),巨噬细胞浸润和凋亡细胞明显减少,炎性因子mRNA的表达明显降低。蛋白水平p38基本无变化,磷酸化的p38表达显著升高。结论 花青素能够减轻脂肪肝小鼠肝脏IR损伤,其机制可能与抑制肝脏再灌注后氧化应激反应和炎症反应,促进p-p38的表达升高有关。

关键词: 脂肪肝, 氧化应激, 炎症反应, 缺血再灌注损伤, 葡萄籽原花青素

Abstract: Objective To explore the protective effects of grape seed proanthocyanidins (GSP) on liver ischemia-reperfusion (IR) in mouse fatty liver models and the possible mechanism. Methods Thirty C57BL/6 mice were randomly divided into 3 groups: sham-operated group (SO group), IR group (mice with steatotic liver treated with distilled water by gavage just before ischemia reperfusion) and GSP group (mice with steatotic liver gavaged with 500 mg/kg GSP). The mice were then sacrificed 6h after reperfusion, and serum and liver samples were collected. The ALT and AST levels in serum were determined and histiological damage on the liver was evaluated. The infiltration of F4/80 positive macrophage cells was detected using immunohistochemistry. The mRNA expressions of TNF-α, IL-6, iNOS, and INF-γ were assayed using real-time reverse transcription PCR. The expression of p38 protein was detected using Western blotting. Results Compared with the IR group, mice in the GSP group exhibited lower levels of serum ALT and AST (P<0.05), and milder histological damage. Compared with the IR group, mice in the GSP group had reduced infiltration of macrophages and lower mRNA expressions of TNF-α, IL-6, iNOS and INF-γ in the liver tissues (P<0.05). The p38 expressions in the three groups had no difference, but the phosphorylated p38 (p-p38) expression in the GSP group was statistically higher than in the other two groups. Conclusion GSP can alleviate steatotic liver IR injury by inhibiting oxidant stress and inflammatory response induced by reperfusion.

Key words: Inflammatory, Grape seed proanthocyanidins, Oxidant stress, Reperfusion injury, Fatty liver

中图分类号: 

  • R574
[1] Ludwig J, Viggiano TR, McGill DB, et al. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease[J]. Mayo Clin Proc, 1980, 55(7): 434-438.
[2] Traber PG, Zomer E. Therapy of experimental NASH and fibrosis with galectin inhibitors[J]. PLoS One, 2013, 8(12): e83481. doi:10.1371/journal.pone.0083481.
[3] Dietrich P, Hellerbrand C. Non-alcoholic fatty liver disease, obesity and the metabolic syndrome[J]. Best Pract Res Clin Gastroenterol, 2014, 28(4): 637-653.
[4] Perkins JD. Saying “Yes” to obese living liver donors: short-term intensive treatment for donors with hepatic steatosis in living-donor liver transplantation[J]. Liver Transpl, 2006, 12(6): 1012-1013.
[5] 汤建军, 江勇, 罗光华, 等. 不同时间的缺血预处理对脂肪肝缺血再灌注损伤的保护作用[J]. 临床肝胆病杂志, 2011, 27(12): 1308-1311. TANG Jianjun, JIANG Yong, LUO Guanghua, et al. The protective effect of different-time-ischemic preconditioning on the reperfusion injury in fatty livers in rats[J]. J Clini Hepatol, 2011, 27(12): 1308-1311.
[6] Zhou HC, Tam NF, Lin YM, et al. Relationships between degree of polymerization and antioxidant activities: a study on proanthocyanidins from the leaves of a medicinal mangrove plant ceriops tagal[J]. PLoS One, 2014, 9(10): e107606. doi:10.1371/journal.pone.0107606.
[7] Ding Y, Dai X, Zhang Z, et al. Proanthocyanidins protect against early diabetic peripheral neuropathy by modulating endoplasmic reticulum stress[J]. J Nutr Biochem, 2014, 25(7): 765-772.
[8] Pons Z, Guerrero L, Margalef M, et al. Effect of low molecular grape seed proanthocyanidins on blood pressure and lipid homeostasis in cafeteria diet-fed rats[J]. J Physiol Biochem, 2014, 70(2): 629-637.
[9] Zhang Z, Zheng L, Zhao Z, et al. Grape seed proanthocyanidins inhibit H2O2-induced osteoblastic MC3T3-E1 cell apoptosis via ameliorating H2O2-induced mitochondrial dysfunction[J]. J Toxicol Sci, 2014, 39(5): 803-813.
[10] Terra X, Montagut G, Bustos M, et al. Grape-seed procyanidins prevent low-grade inflammation by modulating cytokine expression in rats fed a high-fat diet[J]. J Nutr Biochem, 2009, 20(3): 210-218.
[11] Liu CM, Ma JQ, Liu SS, et al. Proanthocyanidins improves lead-induced cognitive impairments by blocking endoplasmic reticulum stress and nuclear factor-κB-mediated inflammatory pathways in rats[J]. Food Chem Toxicol, 2014, 72(10): 295-302.
[12] Ishimaru M, Yusuke N, Tsukimoto M, et al. Purinergic signaling via P2Y receptors up-mediates IL-6 production by liver macrophages/Kupffer cells[J]. J Toxicol Sci, 2014, 39(3): 413-423.
[13] Tsutsui H, Nishiguchi S. Importance of Kupffer cells in the development of acute liver injuries in mice[J]. Int J Mol Sci, 2014, 15(5): 7711-7730.
[14] Zhou C, Shi X, Huang H, et al. Montelukast attenuates neuropathic pain through inhibiting p38 mitogen-activated protein kinase and nuclear factor-kappa B in a rat model of chronic constriction injury[J]. Anesth Analg, 2014, 118(5): 1090-1096.
[15] Nadeem A, Siddiqui N, Alharbi NO, et al. Acute glutathione depletion leads to enhancement of airway reactivity and inflammation via p38MAPK-iNOS pathway in allergic mice[J]. Int Immunopharmacol, 2014, 22(1): 222-229.
[16] 张宇, 蒋建新, 吉善和, 等. 细菌内毒素对枯否细胞丝裂原活化蛋白激酶家族的影响[J]. 解放军医学杂志, 2002, 27(1): 5-7. ZHANG Yu, JIANG Jianxin, JI Shanhe, et al. Protein expression and phosphorylation of mitogen-activated protein kinases inmurine kupffer cells induced by lipopolysaccharide (LPS)[J]. Med J Chin PLA, 2002, 27(1): 5-7.
[17] Kobayashi M, Takeyoshi I, Yoshinari D, et al. P38 mitogenactivated protein kinase inhibition attenuates ischemiareperfusioninjury of the rat liver[J]. Surgery, 2002, 131(3): 344-349.
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