基础研究 Open Access
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
世界华人消化杂志. 2003-10-15; 11(10): 1497-1499
在线出版日期: 2003-10-15. doi: 10.11569/wcjd.v11.i10.1497
珍珠梅水提物对大鼠肝损伤的保护作用
张学武, 朴龙, 刘超, 孙权, 金海玲, 尹宗柱
张学武, 孙权, 金海玲, 尹宗柱, 延边大学医学院生物化学与分子生物学教研室 吉林省延吉市 133000
张学武, 男, 1973-05-15年生, 汉族, 讲师, 医学硕士. 主要从事肝脏生物化学. 研究工作, 已发表论文10篇.
朴龙, 延边大学医学院附属医院科教处 吉林省延吉市 133000
刘超, 延边大学医学院附属医院神经内科 吉林省延吉市 133000
通讯作者: 张学武, 133000, 吉林省延吉市局子街121号, 延边大学医学院生物化学与分子生物学教研室. zlz2913835@sina.com
电话: 0433-2660588 传真: 0433-2659795
收稿日期: 2003-03-29
修回日期: 2003-04-20
接受日期: 2003-05-19
在线出版日期: 2003-10-15

目的

研究珍珠梅水提物的保肝作用.

方法

给动物灌胃给药, 用CCl4, D-半乳糖造大鼠急性肝损伤模型, 用比色分析法测定大鼠血清天冬氨酸转氨酶(aspartate transaminase, ALT)、丙氨酸转氨酶(alanine transaminase, AST)的活性; 测定大鼠血清超氧化歧化酶(superoxide dismutase, SOD)、谷胱甘肽过氧化物酶(glutathione perioxidase, GSH-Px)的活性及丙二醛(malondialdehyde, MDA)的含量.

结果

珍珠梅水提物显著降低因CCl4, D-半乳糖所致急性肝损伤大鼠血清ALT, AST的升高; 对急性肝损伤大鼠血清SOD, GSH-PX的活性有明显的升高作用及降低MDA的含量.

结论

珍珠梅水提物对CCl4, D-半乳糖所致大鼠急性肝损伤有保护作用.

关键词: N/A

引文著录: 张学武, 朴龙, 刘超, 孙权, 金海玲, 尹宗柱. 珍珠梅水提物对大鼠肝损伤的保护作用. 世界华人消化杂志 2003; 11(10): 1497-1499
Studies on liver-protection of Sorbaria sorbifolia aqueous extract
Xue-Wu Zhang, Long Piao, Chao Liu, Quan Sun, Hai-Ling Jin, Zong-Zhu Yin
Xue-Wu Zhang, Quan Sun, Hai-Ling Jin, Zong-Zhu Yin, Department of Biochemistry and Molecular Biology, Yanbian University College of Medicine, Yanji133000, Jilin Province, China
Long Piao, Department of Science and Education, Affiliated Hospital, Yanbian University College of Medicine, Yanji133000, Jilin Province, China
Chao Liu, Department of Neurology, Affiliated Hospital, Yanbian University College of Medicine, Yanji133000, Jilin Province, China
Corresponding author: Xue-Wu Zhang, Department of Biochemistry and Molecular Biology, Yanbian University College of Medicine. 121 Juzi Street, Yanji133000, Jilin Province, China. zlz2913835@sina.com
Received: March 29, 2003
Revised: April 20, 2003
Accepted: May 19, 2003
Published online: October 15, 2003

AIM

To study the liver-protection effects of Sorbaria sorbifolia aqueous extract.

METHODS

Sorbaria sorbifolia was perfused into stomach of the rats with liver injury induced by carbon tetrachloride and D-galactosamine. The activities of serum aspartate transaminase (AST), alanine transaminase (ALT), superoxide dismutase (SOD), glutathione perioxidase (GSH-PX), and malondialdehyde (MDA) were investigated by using colorimetric method.

RESULTS

The aqueous extract of Sorbaria sorbifolia significantly reduced serum ALT and AST in acute liver-injury induced by carbon tetrachloride and D-galactosamine, the activities of SOD and GSH-PX were signficantly higher in treated group than that in model group, and the MDA content in treated group was lower than that in model group.

CONCLUSION

The aqueous extract of Sorbaria sorbifolia has protecting effects for rats with acute hepatic injury induced by carbon tetrachloride and D-galactosamine.

Key Words: N/A


0 引言

珍珠梅(sorbaria sorbifolia)属蔷薇科植物, 又称山高粱、八木条、珍珠杆, 广泛分布于云南、贵州、四川、湖北、甘肃、宁夏及东北, 有活血化瘀、消肿止痛, 治骨折、跌打损伤的作用, 我们曾研究珍珠梅乙酸乙酯提取物对CCl4所致大鼠急性肝损伤的保护作用[1]. 本次实验研究珍珠梅水提物的保肝作用.

1 材料和方法
1.1 材料

珍珠梅采集于吉林省延吉市市郊. 水提取物: 珍珠梅茎、叶、花, 加水煎煮三次, 做成水煎液, 浓缩成1 mL含有生药4 g. SOD, MDA, GSH-PX试剂盒购置南京建成生物工程研究所, 联苯双酯由浙江温岭制药厂生产, 批号: 980813, 其他试剂均为国产分析纯. Wistar大鼠, 雌雄各半, 质量为180-200 g, 由延边大学医学院动物科提供.

1.2 方法

1.2.1 CCl4致大鼠急性肝损伤 取Wistar大鼠50只, 随机分为正常组、模型组、大、小剂量给药组、阳性对照组组5个组. 给药组按10 g/kg、5 g/kg剂量、阳性对照组按0.2 g/kg剂量灌胃联苯双酯, 正常组、模型组以等体积生理盐水灌胃, 共5 d. 第4 d, 模型组、给药组和阳性对照组按5.0 mL/kg剂量背部皮下注射CCl4, 正常组背部皮下注射等体积生理盐水. 皮下注射CCl4 24 h后, 摘眼球取血, 分离血清. 用全自动生化分析仪检测血清ALT, AST的活性, 用比色分析法检测血清SOD, GSH-PX的活性及MDA的含量.

1.2.2 D-半乳糖致大鼠急性肝损伤 取Wistar大鼠50只, 随机分为正常组、模型组、大、小剂量给药组、阳性对照组组5个组. 给药组按10 g/kg、5 g/kg剂量, 阳性对照组按0.2 g/kg联苯双酯灌胃, 正常组、模型组以等体积生理盐水灌胃, 共5 d. 第4 d, 模型组和给药组按0.5 g/kg剂量腹腔注射D-半乳糖, 正常组腹腔注射等体积生理盐水. 腹腔注射24 h后, 摘眼球取血, 分离血清. 用全自动生化分析仪检测血清ALT、AST的活性, 用比色分析法检测血清SOD、GSH-PX的活性及MDA的含量.

统计学处理 数据以mean±SD表示, 应用SPSS-10.0统计软件进行方差分析.

2 结果
2.1 CCl4致急性肝损伤

珍珠梅水提取物明显降低CCl4所致急性肝损伤大鼠血清ALT, AST的升高, 同时升高SOD, GSH-Px的活力, 降低MDA的含量(P<0.01或P<0.05, 表1).

表1 珍珠梅水提物对CCl4所致急性肝损伤大鼠血清ALT, AST, SOD, GSH-Px, MDA的影响 (mean±SD, n =10).
分组CCl4 (mL/kg)ALT (nkat/L)AST(nkat/L)SOD(nkat/L)GSH-Px(nkat/L)MDA(nmol/L)
正常组01 396±135b2 601±752b666±26a130±35a1.3±0. 6a
模型组5.01 2608±4 46411 595±4 336307±153103 ±152.7±0.8
大剂量组5.05 413±2 097a4 160±1 476a410±50a142±8b1.8±0.7a
小剂量组5.05 850±1 994a5 221±1 665a525±125a137±20b1.3±1.0a
阳性对照组5.02 279±1 901a2 523±950a591±169a166±26b1.5±0.5a
2.2 D-半乳糖致急性肝损伤

珍珠梅水提取物明显降低D-半乳糖所致急性肝损伤大鼠血清ALT、AST的升高, 同时升高SOD、GSH-Px的活力, 降低MDA的含量(P<0.01或P<0.05, 表2).

表2 珍珠梅水提物对D-半乳糖所致急性肝损伤大鼠血清ALT, AST, SOD, GSH-PX, MDA的影响 (mean±SD, n =10).
分组CCl4 (mL/kg)ALT (nkat/L)AST(nkat/L)SOD(nkat/L)GSH-Px(nkat/L)MDA(nmol/L)
正常组01 396±135a2 601±752b666±26a130±35a1.3±0.6a
模型组0.510 881±3 9549 238±3 572367±114121 ±93.0±0.3
大剂量组0.54 600±1 894a4 160±1 476a423±26a151±8b1.4±0.9a
小剂量组0.54 168±334a4 955±1 416a475±154a153±20a1.2±1.0a
阳性对照组0.52 279±1 901a2 523±950a591±169a166±26b1.5±0.5a
3 讨论

近年来研究表明, 肝损伤是多因素参与的复杂过程, 细胞质内ALT、AST渗入血液, 结果血清ALT、AST活性升高[2-13]. 自由基和脂质过氧化在肝损伤中起着十分重要的作用. D-半乳糖引起肝细胞内钙离子增多, 镁离子减少, 钙离子增多时抑制线粒体的呼吸功能, 激活磷脂酶, 分解膜磷脂, 破坏溶酶体膜, 使蛋白水解酶释放, 并使黄嘌呤脱氢酶转化为黄嘌呤氧化酶, 加速氧自由基的产生, 从而使损伤进一步加剧[14-16]. 自由基是人体正常生化过程的中间产物, 在机体正常及病理过程中都存在, 同时机体在进化过程中获得了清除氧自由基的一些酶, 如SOD, GSH-Px. 因此, 只有当自由基产生过多或者机体内的酶系统过少时才导致疾病.氧自由基可促使不饱和脂肪自由基形成, 脂质自由基可引起细胞膜的流动性、通透性和完整性的破坏, 进而使其双层结构发生断裂, 引起膜镶嵌的一系列酶的排列紊乱, 功能丧失, 细胞的能量产生系统瘫痪. SOD、GSH-Px的变化可以间接地反应疾病情况下自由基的变化. SOD为高效的清道夫, 可抑制自由基启动的脂质过氧化, GSH-Px是重要的催化过氧化氢分解的酶, 他特异地催化还原性GSH对过氧化氢的还原反应, 从而起到保护细胞膜结构与功能的完整作用. MDA是脂质过氧化的最终产物, 可严重破坏细胞膜的结构, 导致细胞肿胀、坏死, 其含量反映了组织过氧化的损伤程度[17-35].本实验中给药组SOD, GSH-Px较模型组显著升高, 而MDA含量显著降低, 这说明珍珠梅水提物的保肝机制与其对抗自由基脂质过氧化密切相关.

1.  金 海玲, 张 学武, 赵 红, 柳 明洙, 陈 丽艳, 尹 宗柱. 珍珠梅提取物对四氯化碳所致大鼠急性肝损伤的保护作用. 世界华人消化杂志. 2002;10:783-786.  [PubMed]  [DOI]
2.  Wei HS, Li DG, Lu HM, Zhan YT, Wang ZR, Huang X, Zhang J, Cheng JL, Xu QF. Effects of AT 1 receptor antagonist, losartan, on rat hepatic fibrosis induced by CCl4. World J Gastroenterol. 2000;6:540-545.  [PubMed]  [DOI]
3.  Wei HS, Lu HM, Li DG, Zhan YT, Wang ZR, Huang X, Cheng JL, Xu QF. The regulatory role of AT 1 receptor on activated HSCs in hepatic fibrogenesis: effects of RAS inhibitors on hepatic fibrosis induced by CCl4. World J Gastroenterol. 2000;6:824-828.  [PubMed]  [DOI]
4.  田 耕, 于 皆平, 罗 和生, 余 保平, 李 建英. 环氧合酶-2在急性肝损害中的作用机制. 世界华人消化杂志. 2002;10:24-27.  [PubMed]  [DOI]
5.  Giffen PS, Pick CR, Price MA, Williams A, York MJ. Alpha-glutathione S-transferose in the assessment of hepatotoxicity-its diagnostic utility in comparison with other recognized markers in the Wistar Han rat. Toxicol Pathol. 2002;30:365-372.  [PubMed]  [DOI]
6.  Sotelo-Felix JI, Martinez-Fong D, Muriel P, Santillan RL, Castillo D, Yahuaca P. Evaluation of the effectiveness of Rosmarinus officinalis(Lamiaceae) in the alleviation of carbon tetrachloride-induced acute hepototoxicity. J Ethnopharmacol. 2002;81:145-154.  [PubMed]  [DOI]
7.  Hung DY, Chang P, Cheung K, McWhinnney B, Masci PP, Weiss M, Roberts MS. Cationic drug pharmacokinetics in diseased livers determined by fibrosis index, hepatic protein content microsomal activity, and nature of drug. J Pharmacol Exp Ther. 2002;301:1079-1087.  [PubMed]  [DOI]
8.  Stedman C. Herbal hepatotoxicity. Semin Liver Dis. 2002;22:195-206.  [PubMed]  [DOI]
9.  Nakade Y, Yoneda M, Nakamura K, Makino I, Terano A. Involvement of endogenous CRF in carbon tetrachloride-induced acute liver injury in rats. Am J Physiol Regul Integrcomp Physicl. 2002;282:R1782-1788.  [PubMed]  [DOI]
10.  Shimizu H, Uetsuka K, Nakayama H, Doi K. Carbon tetrachloride-induced acute liver injury in Mini and Wistar rats. Exp Toxicol Pathol. 2001;53:11-17.  [PubMed]  [DOI]
11.  Bruckner JV, Ramanathan R, Lee KM, Muralidhara S. Mechanisms of circadian rhythmicity of carbon tetrachloride hepatotoxicity. J Pharmacol Exp Ther. 2002;300:273-281.  [PubMed]  [DOI]
12.  Zhao Y, Liu L, Fu Z, Lu Y. Protective effect of Huyin decoction on acute hepatic injury induced by CCl4. in mice. Zhong Yao Cai. 2001;24:886-887.  [PubMed]  [DOI]
13.  Campo GM, Squadrito F, Ceccarelli S, Calo M, Avenoso A, Campo S, Squadrito G, Altavilla D. Reduction of carbon tetrachloride-induced rat liver injury by IRFI042, a novel dual vitamin E-like antioxidant. Free Radic. 2001;34:379-393.  [PubMed]  [DOI]
14.  Lemire BD, Oyedotun KS. The Saccharomyces cerevisiae mitochondrial succinate: ubiquinone oxidoreductase. Biochim Biophys Acta. 2002;1553:102-116.  [PubMed]  [DOI]
15.  Ishihara A, Ohira Y, Tanaka M, Nishikawa W, Ishioka N, Higashibata A, Izumi R, Shimazu T, Ibata Y. Cell body size and succinate dehydrogenase activity of spinal motoneurons innervating the soleus muscle in mice, rats, and cats. Neurochem Res. 2001;26:1301-1304.  [PubMed]  [DOI]
16.  Wu Y, Liu C, Chen Q. Effect of acupuncture on enzymology of motor neuron of anterior horn of experimental spinal cord injury in rats. Zhonhguo Zhongxiyi Zazhi. 1999;19:740-742.  [PubMed]  [DOI]
17.  Usta J, Kreydiyyeh S, Bajakian K, Nakkash-Chmaisse H. In vitro effect of eugenol and cinnamaldehyde on membrane potential and respiratory chain complexes in isolated rat liver mitochondria. Food Chem Toxicol. 2002;40:935-940.  [PubMed]  [DOI]
18.  Brusque AM, Borba R, Schuck PF, Dalcin KB, Ribeiro CA, Silva CG, Wannmacher CM, Dutra-Filho CS, Wyse AT, Briones P. Inhibition of the mitochondrial respiratory chain complex activities in rat cerebral cortex by methylmalonic acid. Neurochem Int. 2002;40:593-601.  [PubMed]  [DOI]
19.  李 军, 孙 梅, 韩 梅. 宫内窒息鼠损伤肝NO, SOD和NOS的变化. 世界华人消化杂志. 2002;10:177-181.  [PubMed]  [DOI]
20.  崔 云华, 王 小玲, 刘 晴, 刘 平. 丹参酸乙的抗氧化作用对大鼠肝星状细胞增生的影响. 世界华人消化杂志. 2002;10:317-319.  [PubMed]  [DOI]
21.  赵 佐庆, 朱 文侠, 刘 福兰, 张 玲. 犬小肠缺血再灌注后氧自由基的改变意义. 世界华人消化杂志. 2001;9:921-924.  [PubMed]  [DOI]
22.  陈 文慧, 刘 平, 徐 光福, 陆 雄, 熊 卫国, 李 风华, 刘 成海. 脂质过氧化在二甲基亚硝胺大鼠肝纤维化形成过程中的作用. 世界华人消化杂志. 2001;9:645-648.  [PubMed]  [DOI]
23.  杨 俊涛, 王 正国, 朱 佩方. 谷氨酰胺对胃肠手术患者血浆还原型谷胱甘肽水平的影响. 世界华人消化杂志. 1999;7:867-868.  [PubMed]  [DOI]
24.  刘 成, 胡 义扬, 王 润平, 刘 成海, 刘 平. 丹酚酸A抗过氧化鼠肝损伤的作用. 世界华人消化杂志. 1999;7:570-572.  [PubMed]  [DOI]
25.  藤 书玲, 武 希润, 习 玲. 一氧化氮和自由基对大鼠急性肝损伤的作用. 世界华人消化杂志. 1999;7:222-223.  [PubMed]  [DOI]
26.  Zhou JF, Cai D, Zhu YG, Yang JL, Peng CH, Yu YH. A study on relationship of nitric oxide, oxidation, peroxidation, lipoperoxidation with chronic chole-cystitis. World J Gastroenterol. 2000;6:501-507.  [PubMed]  [DOI]
27.  Huang ZS, Wang ZW, Liu MP, Zhong SQ, Li QM, Rong XL. Protective effects of polydatin against CCl4杋nduced injury to primarily cultured rat hepatocytes. World J Gastroenterol. 1999;5:41-44.  [PubMed]  [DOI]
28.  Barilja G. Endogenous oxidative stress: relationship to aging, longevity and caloric restriction. Ageing Res Rev. 2002;1:397-411.  [PubMed]  [DOI]
29.  Iwamoto A, Egashira T, Takayama F, Yamanaka Y, Noguchi T. Change in free radical-related substances in plasma following ischemia-reperfusion in rat liver. Pathophysiology. 2002;8:167-174.  [PubMed]  [DOI]
30.  Lee S, Kim KS, Park Y, Shin KH, Kim BK. In vivo anti-oxidant activities of tectochrysin. Arch Pharm Res. 2003;26:43-46.  [PubMed]  [DOI]
31.  Zhang Z, Yu CX. Effect of melatonin on learning and memory impairment induced by aluminum chloride and its mechanism. Yaoxue Xuebao. 2002;37:682-686.  [PubMed]  [DOI]
32.  Kim KS, Lee S, Lee YS, Jung SH, Park Y, Shin KH, Kim BK. Anti杘xidant activities of the extracts from the herbs of Artemisia apiacea. J Ethnopharmacol. 2003;85:69-72.  [PubMed]  [DOI]
33.  Vaughan JE, Walsh SW. Oxidative stress reproduces placental abnormalities of preeclampsia. Hypertens Pregnancy. 2002;21:205-223.  [PubMed]  [DOI]
34.  Lu X, Wang R. Protective effect of magnesium on the damaged cultured endothelial cells induced by oxidized low density lipoprotein. Weisheng Yanjiu. 2002;31:244-246.  [PubMed]  [DOI]
35.  Yasar M, Yildiz S, Mas R, Dundar K, Yildirim A, Akay C, Kaymakcioglu N, Ozisik T, Sen D. The effect of hyperbaric oxygen treament on oxidative stress in experimental acute necrotizing pancreatitis. Physiol Res. 2003;52:111-116.  [PubMed]  [DOI]