吉林大学学报(医学版)

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郁金水煎剂对四氯化碳致急性肝损伤小鼠肝细胞p53和caspase-3表达的影响及其对肝损伤的保护作用

张婉娴1,2,朱彤彤1.3,鲁育铭1,赵丽晶1,刘鹏4 ,赵丽娟1   

  1. 1. 吉林大学基础医学院病理生理学系,吉林 长春 130021;2. 天津市中心妇产科医院新生儿科,天津 300052;3. 吉林大学中日联谊医院骨科,吉林 长春 130033;4. 吉林大学生命科学院,吉林 长春 130012
  • 收稿日期:2013-03-07 出版日期:2014-01-28 发布日期:2014-01-25
  • 通讯作者: 赵丽娟(Tel:0431-85619485,E-mail:titan2003@sina.com) E-mail:titan2003@sina.com
  • 作者简介:张婉娴(1988-),女,天津市人,在读医学硕士,主要从事新生儿相关疾病方面的研究。
  • 基金资助:

    吉林省中医药管理局科研基金资助课题(08SYS-067)

Influence of Curcumae Decoction in p53 and caspase-3 expressions in hepatocytes of mice with acute hepatic injury induced with carbon tetrachloride and its protective effect on liver injury

ZHANG Wan-xian1,2, ZHU Tong-tong1.3, LU Yu-ming1, ZHAO Li-jing1, LIU Peng4, ZHAO Li-juan1   

  1. 1.   Department of Pathophysiology,School of Basic Medical Sciences,Jilin University,Changchun 130021,China;2. Department of Neonatology,Tianjin Central Hospital of Gynecology and Obstetrics,Tianjin 300052,China;3. Department of Orthopedics,China-Japan Union Hospital,Jinlin University,Changchun 130033,China;4. College of Life Science,Jilin University,Changchun 130012,China
  • Received:2013-03-07 Online:2014-01-28 Published:2014-01-25

摘要:

目的:探讨单味郁金水煎剂对四氯化碳(CCl4)致急性肝损伤小鼠肝细胞凋亡基因p53和caspase-3蛋白表达的影响,阐明郁金对肝损伤保护作用的机制。方法:ICR小鼠60只,随机分为空白对照组(等体积生理盐水)、模型组(等体积生理盐水)、郁金低剂量组(2.5 g/kg)、郁金中剂量组(5.0 g/kg)、郁金高剂量组(10.0 g/kg)和阳性药组 (甘利欣 22.5 mg/kg);连续给药7 d后,除空白对照组外各组小鼠均通过CCl4复制小鼠急性肝损伤模型。计算肝指数,测定血清丙氨酸氨基转移酶(ALT)活性,HE染色观察肝组织形态学变化;RT-PCR法检测肝细胞p53基因转录情况;免疫组织化学法检测肝细胞caspase-3蛋白表达。结果:与空白对照组比较,模型组小鼠肝指数明显增加(P<0.05);与模型组比较,各给药组小鼠肝指数明显降低(P<0.05)。与空白对照组比较,模型组小鼠血清ALT增高(P<0.01);与模型组比较,阳性药组及郁金高、中剂量组小鼠血清ALT明显降低(P<0.05)。肝脏形态学变化,肉眼观察,空白对照组小鼠肝脏呈现粉红色,质软而富有弹性,模型组小鼠肝脏明显肿大、呈微黄色,表面可见散在点状及片状黄褐色斑点,质脆,各给药组小鼠肝脏大小、颜色及质地均界于空白对照组与模型组之间,且表面无明显黄褐色斑点;镜下观察,空白对照组小鼠肝脏结构正常,模型组小鼠细胞呈明显局灶性气球样变、水样变性和死亡,而阳性药组和郁金中、高剂量组小鼠与模型组比较肝组织上述病灶数量减少。与空白对照组比较,模型组小鼠肝细胞p53基因转录明显增强(P<0.05);与模型组比较,郁金高剂量组小鼠肝细胞p53基因转录显著减弱 (P<0.05)。与模型组比较,郁金给药组小鼠肝细胞caspase-3蛋白表达减弱。结论:郁金对CCl4致小鼠急性肝损伤有一定的拮抗作用,其机制之一可能与下调凋亡基因p53和caspase-3蛋白的表达、阻碍肝细胞凋亡有关。

关键词: 郁金, 急性肝损伤, 四氯化碳, p53基因, caspa

Abstract:

Abstract:Objective To investigate the influence of Curcumae decoction in p53 and caspase-3 expressions in hepatocytes of the mice with acute hepatic injury induced with carbon tetrachloride (CCl4),and to clarify the mechanisms of protective effect of Curcumae decoction on acute hepatic injury. Methods 60 ICR mice were randomly divided into blank  control group (saline for equal volume),model group (saline for equal volume),positive drug group (diammonium glycyrrhizinate),low dose of  Curcumae group (2.5 g/kg),middle dose of Curcumae group (5.0 g/kg) and high dose of  Curcumae group (10.0 g/kg).The acute hepatic injury mouse models were established with CCl4 after being given drugs for 7 d.The liver indexes were calculated,and the activities of alanine aminotransferase (ALT) in serum were detected and the pathological changes of liver tissue were observed.The gene transcription level of p53 in hepatocytes was examined by RT-PCR and the expression of caspase-3 protein in liver tissue was detected by immunohistochemistry. Results Compared with blank  control group,the liver index of the mice in model group was significantly increased (P<0.05);compared with model group,the liver indexes of the mice in different Curcumae groups were decreased (P<0.05). Compared with blank control group,the serum ALT activity of the mice in model group was increased (P<0.01),and the ALT activities of mice in positive drug group,high and middle doses of Curcuame groups were clearly decreased (P<0.05). The livers of the mice in blank  control group were red,soft and elastic,the livers in model group were swell,a little yellow,and having some filemot spalash.Microscopically,the liver tissue in blank control group was in gear,there were a lot of hepatocytes swell,inflammatory infiltration,balloon liked denaturalization and hepatocytes death of the mice in model group,but the lesions became much slighter in Curcumae groups.The gene transcription level of p53 in model group was increased compared with blank control group (P<0.05),and the gene transcription level of p53 in high dose of  Curcumae group was significantly decreased (P<0.05).The caspase-3 protein expressions in liver tissue of the mice in Curcumae groups were obviously decreased. Conclusion Curcumae can protect the liver from acute hepatic injury induced with CCl4 in the mice,its mechanism may be related to reducing  the gene transcription level of p53 and the expression of caspase-3 and prevent the hepatocytes from apoptosis.

Key words: Curcumae;acute hepatic injury;carbon tetrachloride, p53 gene;caspase-3 ,  

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