异常黑胆质成熟剂对异常黑胆质型肝癌病证大鼠模型肝脏形态学的影响
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摘要
为探讨异常黑胆质成熟剂对异常黑胆质型肝癌病证大鼠模型肝脏形态学的影响,按照维吾尔医模型建立标准,采用干寒环境、干寒饲料和异常物理刺激等多重因素复合作用,建立维医异常黑胆质证载体动物模型,在此基础上,通过饮用灭菌食用水配制浓度为0.1 mg/m L二乙基亚硝胺(DEN)溶液建立异常黑胆质型肝癌病证载体大鼠模型,并用大、中、小不同剂量(6.0、3.0、1.5 g/kg)异常黑胆质成熟剂进行全程干预,共分为病证模型组、小剂量组、中剂量组、大剂量组、正常对照组、肝癌对照组6组,每组24只。干预20周时处死大鼠,对肝脏的病理变化和超微结构进行观察。研究发现,20周时,低剂量组与病证模型组相比,形态无明显差异,高剂量组和中剂量组与病证模型组相比,具有肝细胞结缔组织增生减少、间质炎性细胞浸润程度明显减轻、肝细胞水肿程度减轻等病理表现及肝细胞内细胞器分布不均匀、肝糖原和线粒体逐渐减少等超微结构明显变化。研究表明,异常黑胆质成熟剂对异常黑胆质型肝癌病证模型的肝脏组织形态改变有一定的保护和修复作用。
To find how the abnormal savda munziq affects the hepatocarcinoma cell morphology of abnormal savda rat, rats were under the stimulations of dry cold environment and dry cold feed and abnormal physical stimulation to establish a model with the abnormal savda according to Uyghur medicine theory. They were raised by sterilized edible water with 0.1 mg/m L of diethylnitrosamine(DEN) solution to establish the hepatocarcinoma model. The rats were treated with high and middle and low doses(6.0, 3.0, 1.5 g/kg) in three groups during the whole period. There were the abnormal savda and HCC model group, low dosage group,middle dosage group, high dosage group, normal control group, and HCC control group, with 24 rats in each group. The animals were anesthetized and killed at the 20 th week, then HE staining and observation of morphological characteristics of livers were performed. The results revealed the followings: Albeit no significant differences were found between low dosage group and model groups in morphology, compared with the model groups in high dosage or middle dosage, hyperplasia of connective tissue decreases and the degree of interstitial infiltration of inflammatory cells reduced significantly, cell edema alleviated, reductions of organelle nonuniform, glycogen and mitochondria were significant in the model group. Our findings indicate that the abnormal savda munziq can depress the transformation of hepatocyte to hepatocellular carcinoma in the process of chimeric rats.
To find how the abnormal savda munziq affects the hepatocarcinoma cell morphology of abnormal savda rat, rats were under the stimulations of dry cold environment and dry cold feed and abnormal physical stimulation to establish a model with the abnormal savda according to Uyghur medicine theory. They were raised by sterilized edible water with 0.1 mg/m L of diethylnitrosamine(DEN) solution to establish the hepatocarcinoma model. The rats were treated with high and middle and low doses(6.0, 3.0, 1.5 g/kg) in three groups during the whole period. There were the abnormal savda and HCC model group, low dosage group,middle dosage group, high dosage group, normal control group, and HCC control group, with 24 rats in each group. The animals were anesthetized and killed at the 20 th week, then HE staining and observation of morphological characteristics of livers were performed. The results revealed the followings: Albeit no significant differences were found between low dosage group and model groups in morphology, compared with the model groups in high dosage or middle dosage, hyperplasia of connective tissue decreases and the degree of interstitial infiltration of inflammatory cells reduced significantly, cell edema alleviated, reductions of organelle nonuniform, glycogen and mitochondria were significant in the model group. Our findings indicate that the abnormal savda munziq can depress the transformation of hepatocyte to hepatocellular carcinoma in the process of chimeric rats.
引文
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[15]阿布力孜·阿卜杜扎依尔,哈木拉提·吾甫尔,玉苏甫·吐尔逊,等.异常黑胆质成熟剂对异常黑胆质性癌病证模型肝硬化期的肝脏形态学的影响[J].科技导报,2011,29(28):68-73.Abduzayir Abliz,Upur Halmurat,Tursun Yusup,et al.Effect ofabnormal savda munziq on morphological structure of hepatic tissuein hepatocirrhosis phase of hepatocarcinoma carrying abnormal savdamodel[J].Science&Technology Review,2011,29(28):68-73.
[16]依马木·麦麦提依明,热沙来提·阿不都瓦依特,买热艳木·艾尔肯,等.STAT3基因在异常黑胆质型肝癌病证大鼠模型肝脏中的表达及意义[J].新疆医科大学学报,2014,10(5):540-544.Mamatimin Imam,Abduwayit Risalat,Arkin Maryam,et al.Expression and significance of STAT3 gene in abnormal savda diseasecarring hepatocellular carcinoma rat model of liver[J].Journal ofXinjiang Medical University,2014,10(5):540-544.
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[20]Husain K T,Sarwat S.Effect of Aegle marmelos on DEN initiated and2-AAF promoted hepatocarcinogenesis achemopreventive study[J].Toxicology Mechanisms and Methods,2011,21(6):453-462.
[21]Leng T,Liu N,Dai Y,et al.Dissection of DEN-induced plateletproteome changes reveals the progressively dys-regulated pathwaysindicative of hepatocarcinogenesis[J].Journal of Proteome Research,2010,9(12):6207-6219.
[22]Takakazu N,Junichi O,Yuki F,et al.Preventive effect of JTE-522,a selective cyclooxygenase-2 inhibitor,on DEN-inducedhepatocarcinogenesis in rats[J].Medicine Science Entry forBiomedicine&Pharmacotherapy.2010,64(5):319-326.
[23]Anuradha S,Sarwat S.Evaluation of possible mechanisms of protectiverole of tamarix gallica against DEN initiated and 2-AAF promotedhepatocarcinogenesis in male Wistar rats[J].Life Sciences.2006,79(15):1456-1465.
[24]哈木拉提,阿不都热依木,阿不都艾尼.维吾尔医成熟剂和清除剂抗活性氧的作用研究[J].中国民族医药杂志,2000,6(3):30-32.Halmurat,Abduriyim,Abdughini.Effects of abnormal savda munziqand mushil on cleaning oxygen radical[J].Journal of Medicine&Pharmacy of Chinese Minorities,2000,6(3):30-32.
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[2]Srivatanakul P,Sriplung H,Deerasamee S.Epidemiology of liver cancer:An overview[J].Asian Pacific Journal of Cancer Prevention,2004,5(2):118-125.
[3]上海医药.《2012中国肿瘤登记年报》发表[J].上海医药,2013,34(4):7.Shanghai Medical&Pharmaceutical Journal.The 2012 annual report ofChina umor published[J].Shanghai Medical&Pharmaceutical Journal,2013,34(4):7.
[4]哈木拉提·吾甫尔.维吾尔医气质、体液论及其现代研究[M].乌鲁木齐:新疆科学技术出版社,2003:34-37,131-133.Upur Halmurat.Modern research of Uighur medicine temperamentbody fluid theory[M].Urumq:Xinjiang Science Technology PublishingCompany,2003:34-37,131-133.
[5]买吾拉尼江·依孜布拉,巴吐尔·买买提明,娜祖科·库尔班塔依,等.基于NMR代谢组学方法研究异常黑胆质成熟剂对异常黑胆质型2型糖尿病大鼠的作用机制[J].新疆医科大学学报,2013,34(4):411-418.Hizbilla Mawlanjan,Mamtimin Batur,Kurbantay Nazuk,et al.NMRmetabonomic study of abnormal savda munziq's mechanism of effect tothe abnormal savda syndrome type 2 diabets rats[J].Journal of XinjiangMedical University,2013,34(4):411-418.
[6]努尔曼·麦麦提,阿衣努尔·买提斯迪克,阿不都热依木·玉苏甫,等.异常黑胆质成熟剂颗粒对肾血管性高血压大鼠血压和血脂的影响[J].中国中医基础医学杂志,2013,19(7):770-772.Mamat Nuerman,Matsidik Ayinuer,Yusup Abduriyim,et al.Effects ofabnormal savda mature granules on blood lipid and blood pressure inrenovascular hypertensive rats[J].Chinese Journal of Basic Medicine inTraditional Chinese Medicine,2013,19(7):770-772.
[7]努尔曼·麦麦提,阿孜古丽·吐鲁洪,阿衣努尔·买提斯迪克,等.异常黑胆质成熟颗粒对肾血管性高血压大鼠的降压作用[J].新疆医科大学学报,2013,36(6):741-743.Mamat Nuerman,Turghun Arzigul,Matsidik Ayinuer,et al.Effect of abnormal savda munziq granular on renovascular hypertensive rats tolower blood pressure[J].Journal of Xinjiang Medical University,2013,36(6):741-743.
[8]李春燕,哈木拉提·吾甫尔,阿衣努尔·买提斯迪克,等.维吾尔医学异常黑胆质型支气管哮喘与肝功能、肾功能改变的相关性研究[J].新疆医科大学学报,2013,9(7):12-14.Li Chunyan,Upur Halmurat,Maitisidike Ayinuer,et al.Study onrelationship between abnormal savda asthma,liver function and renalfunction[J].Journal of Xinjiang Medical University,2013,9(7):12-14.
[9]阿不都热依木·玉素甫,李林,哈木拉提·吾甫尔,等.维医异常体液分型及其与氧化-抗氧化系统关系的研究[J].中国中医基础医学杂志,2004,10(8):61-63.Abduriyim Yusup,Li Lin,Upur Halmurat,et al.The relationshipbetween different abnormal hilit in Uygur traditional medicineand oxidation-antioxidation[J].China Journal of Basic Medicine inTraditional Chinese Medicine,2004,10(8):61-63.
[10]哈木拉提·吾甫尔,吾尔古丽·阿卜杜来海提,阿衣努尔·买提斯迪克.基于德尔菲专家咨询法对肿瘤异常黑胆质病证异常体液成熟和清除标准的研究[J].科技导报,2012,30(36):61-65.Upur Hamulati,Abdulahat Hurigul,Matsidik Ayinuer.Matured andremoved syndrome characteristics criteria of abnormal hilit forabnormal savda type tumor with Uighur medicine based on Delphimethod[J].Science&Technology Review,2012,30(36):61-65.
[11]易沙克江·马合穆德,阿不都热依木·卡地尔.中国医学百科全书:维吾尔医学[M].上海:上海科学技术出版社,2005:89-94.Mahmud Ishakjan,Kadir Abdiryim.Traditional Uighur medicine ofChina medical encyclopaedia[M].Shanghai:Shanghai Scientific andTechnical Publishers,2005:89-94.
[12]阿地力江·阿不力米提,哈木拉提·吾甫尔,胡汉华,等.异常黑胆质成熟剂对异常黑胆质载体动物模型支配器官细胞超微结构的影响[J].中国中医基础医学杂志,2008,14(1):32-35.Ablimit Adiljan,Upur Halmurat,Hu Hanhua,et al.The effect ofabnormal savda munziq on abnormal savda syndrome animal in organcell ultrastructure[J].China Journal of Basic Medicine in TraditionalChina Medicine,2008,14(1):32-35.
[13]王延蛟,哈木拉提·吾甫尔,依马木·买买提依明,等.异常黑胆质型肝癌病证模型肝脏形态学研究[J].科技导报,2014,32(14):74-78.Wang Yanjiao,Upur Halmurat,Mamatimin Imam,et al.A rat modelof hepatocarcinoma carrying abnormal savda and its morphologicalstudy[J].Science&Technology Review,2014,32(14):74-78.
[14]张有辉,玉苏甫·吐尔逊,哈木拉提·吾甫尔,等.异常黑胆质性肝癌病证模型肝硬化期免疫、内分泌紊乱状态[J].科技导报,2010,28(11):39-42.Zhang Youhui,Tursun Yusup,Upur Halmurat,et al.Disorderedimmune-endocrin network in hepatocirrhosis phase of hepatocarcinomaof carrying abnormal savda model[J].Science&Technology Review,2010,28(11):39-42.
[15]阿布力孜·阿卜杜扎依尔,哈木拉提·吾甫尔,玉苏甫·吐尔逊,等.异常黑胆质成熟剂对异常黑胆质性癌病证模型肝硬化期的肝脏形态学的影响[J].科技导报,2011,29(28):68-73.Abduzayir Abliz,Upur Halmurat,Tursun Yusup,et al.Effect ofabnormal savda munziq on morphological structure of hepatic tissuein hepatocirrhosis phase of hepatocarcinoma carrying abnormal savdamodel[J].Science&Technology Review,2011,29(28):68-73.
[16]依马木·麦麦提依明,热沙来提·阿不都瓦依特,买热艳木·艾尔肯,等.STAT3基因在异常黑胆质型肝癌病证大鼠模型肝脏中的表达及意义[J].新疆医科大学学报,2014,10(5):540-544.Mamatimin Imam,Abduwayit Risalat,Arkin Maryam,et al.Expression and significance of STAT3 gene in abnormal savda diseasecarring hepatocellular carcinoma rat model of liver[J].Journal ofXinjiang Medical University,2014,10(5):540-544.
[17]国家药典委员会.中华人民共和国药典:一部[M].北京:中国医药科技出版社,2005.Chinese Pharmacopoeia Commission.Pharmacopoeia of People'sRepublic of China:First part[M].Beijing:China Medical Science&Technology Press,2005.
[18]国家药典委员会.中华人民共和国卫生部药品标准·维吾尔药分册[M].乌鲁木齐:新疆科技卫生出版社,1999.Chinese Pharmacopoeia Commission.Drug standard of the ministry ofhealth of People's Republic of China·Uighur medicine fascicule[M].Urumqi:Xinjiang Scientific and Technical Publisher,1999.
[19]哈木拉提·吾甫尔.能够使异常黑胆质型体液成熟和清除的药物及其制备方法:中国,C082130082.8[P].2003.Upur Halmurat.Preparation method of abnormal savda munziq andmishill on the effect of abnormal savda syndrome:China,C082130082.8[P].2003.
[20]Husain K T,Sarwat S.Effect of Aegle marmelos on DEN initiated and2-AAF promoted hepatocarcinogenesis achemopreventive study[J].Toxicology Mechanisms and Methods,2011,21(6):453-462.
[21]Leng T,Liu N,Dai Y,et al.Dissection of DEN-induced plateletproteome changes reveals the progressively dys-regulated pathwaysindicative of hepatocarcinogenesis[J].Journal of Proteome Research,2010,9(12):6207-6219.
[22]Takakazu N,Junichi O,Yuki F,et al.Preventive effect of JTE-522,a selective cyclooxygenase-2 inhibitor,on DEN-inducedhepatocarcinogenesis in rats[J].Medicine Science Entry forBiomedicine&Pharmacotherapy.2010,64(5):319-326.
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