异常黑胆质成熟剂对多因素诱发肝癌大鼠模型中p53和p21基因表达的影响
|
摘要
目的探讨维医异常黑胆质成熟剂对多因素诱发肝癌大鼠模型的抗肝癌作用。方法将120只雄性Wistar大鼠随机分为实验组和对照组。实验组大鼠分为异黑肝癌组及异黑成熟剂高、中、低剂量组。根据维吾尔医学理论体系,实验组采用干寒饲养环境、间断足底电刺激、强迫游泳、夹尾等多因素复合作用21d建立异常黑胆质证载体大鼠模型后,在此基础上用二乙基亚硝胺(DEN)诱导20w建立异常黑胆质型肝癌病证大鼠模型,并用异常黑胆质成熟剂按高、中和低(6.0、3.0和1.5g/kg体质量)剂量全程干预,且持续进行异常黑胆质证多因素复合作用直至实验结束。对照组大鼠分为正常对照组和对照肝癌组,在正常饲养环境下未受任何刺激,21d时给予对照肝癌组饮用二乙基亚硝胺(DEN)诱导20w建立肝癌大鼠模型。20w时用免疫组织化学方法检测各组肝组织中p53和p21基因的表达水平。结果与正常对照组比较,对照肝癌组和异黑肝癌组p53和p21基因表达均明显上调(P<0.05);与对照肝癌组比较,异黑肝癌组2种基因表达也均明显上调(P<0.05);与异黑肝癌组比较,异黑肝癌3个剂量组p53和p21基因表达均明显下调(P<0.05)。结论异常黑胆质成熟剂可能通过阻遏该动物模型肝细胞中p53和p21基因的表达而起抗肝癌作用。
Objective To find the anticancer effects of Abnormal Savda Munziq(ASM)in liver cancer rat models which were induced by multiple factors.Methods 120 Wistar rats were randomly divided into experimental group and control group.The experimental group was divided into liver cancer with abnormal savda syndrome group,ASM high dosage group,ASM middle dosage group and ASM low dosage group.Based on the Uyghur medicine theory,the experimental group was established abnormal savda rat model under multifactors,such as dry-cold feeding environment,intermittent planter point stimulation,doingforced swimming test and clipping tails for 21 days.On that basis,the liver cancer rat model with abnormal savda syndrome was induced by using diethylnitrosamine(DEN)for 20 weeks.The rat models were intervened by high,middle and low dosages(6.0,3.0and 1.5g/kg)of ASM in whole course.At the same time,the multifactors were continued till the end.The control group was divided into normal control group and control liver cancer group.The control group was raised at the normal feeding environment and after 21 days the control liver cancer rat model was established in 20 weeks induced by DEN.At the end,expressions of p53 and p21genes in liver tissue were detected by immunohistochemical staining.Results Compared with the normal control group,the expression of p53 and p21gene in control liver cancer group and liver cancer with abnormal savda syndrome group were obviously up-regulated,the difference was statistically significant(P <0.05).Compared with the control liver cancer group,the expression of these two genes in liver cancer with abnormal savda syndrome group were also obviously up-regulated,the difference was statistically significant(P <0.05).Compared the liver cancer with abnormal savda syndrome group,the expressions of p53 and p21genes were down-regulated all in three dosages groups,and the difference was statistically significant(P <0.05).Conclusion ASM probably play its anticancer role in this model by having repression on the expressions of p53 and p21genes.
Objective To find the anticancer effects of Abnormal Savda Munziq(ASM)in liver cancer rat models which were induced by multiple factors.Methods 120 Wistar rats were randomly divided into experimental group and control group.The experimental group was divided into liver cancer with abnormal savda syndrome group,ASM high dosage group,ASM middle dosage group and ASM low dosage group.Based on the Uyghur medicine theory,the experimental group was established abnormal savda rat model under multifactors,such as dry-cold feeding environment,intermittent planter point stimulation,doingforced swimming test and clipping tails for 21 days.On that basis,the liver cancer rat model with abnormal savda syndrome was induced by using diethylnitrosamine(DEN)for 20 weeks.The rat models were intervened by high,middle and low dosages(6.0,3.0and 1.5g/kg)of ASM in whole course.At the same time,the multifactors were continued till the end.The control group was divided into normal control group and control liver cancer group.The control group was raised at the normal feeding environment and after 21 days the control liver cancer rat model was established in 20 weeks induced by DEN.At the end,expressions of p53 and p21genes in liver tissue were detected by immunohistochemical staining.Results Compared with the normal control group,the expression of p53 and p21gene in control liver cancer group and liver cancer with abnormal savda syndrome group were obviously up-regulated,the difference was statistically significant(P <0.05).Compared with the control liver cancer group,the expression of these two genes in liver cancer with abnormal savda syndrome group were also obviously up-regulated,the difference was statistically significant(P <0.05).Compared the liver cancer with abnormal savda syndrome group,the expressions of p53 and p21genes were down-regulated all in three dosages groups,and the difference was statistically significant(P <0.05).Conclusion ASM probably play its anticancer role in this model by having repression on the expressions of p53 and p21genes.
引文
[1]热斯拉特·艾力木,热沙来提·阿不都瓦衣特,哈木拉提·吾甫尔,等.异常黑胆质型肝癌病证动物模型肝硬化期肝脏组织中p53、p21、STAT3和CyclinD1基因的表达[J].世界华人消化杂志,2014,22(21):3083-3088.
[2]阿尤甫江·阿布都热依木,斯坎德尔·白克力,王延娇,等.HPAA组织结构和功能的变化在异常黑胆质型肝癌病证模型中的作用研究[J].新疆医科大学学报,2015,38(3):273-277.
[3]玉素甫·吐尔逊,斯坎德尔·白克力,哈木拉提·吾甫尔,等.异常黑胆质性肝癌病证模型肝硬化期的肝脏形态学研究[J].科技导报,2010,28(24):82-88.
[4]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.
[5]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.
[6]王延蛟,热沙来提·阿不都瓦衣特,哈木拉提·吾甫尔,等.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[J].科技导报,2015,33(11):84-89.
[7]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,02130082.8[P].2003-04-06.
[8]KIM S,AN SS.Role of p53isoforms and aggregations in cancer[J].Medicine,2016,95(26):e3993.
[9]KASTAN MB.Commentary on participation of p53protein in cellular response to DNA damage[J].Cancer Res,2016,76(13):3663-3665.
[10]张潇荟,姜英,杨军.p53非依赖性信号通路在DNA损伤致细胞凋亡中的研究进展[J].浙江大学学报,2013,42(2):217-223.
[11]王娅杰,孙华,刘耕陶,等.p53在DNA损伤反应中的研究进展[J].药学学报,2011,46(12):1413-1419.
[12]李哲夫,宋敏,王一,等.肝癌组织中HBsAg、PCNA、p53及p21表达的意义[J].中国普通外科杂志,2013,12(3):215-216.
[13]CHENG M,HE B,WAN T,et al.5-Fluorouracil Nanoparticles Inhibit Hepatocellular Carcinoma via Activation of the p53Pathway in the O-rthotopic Transplant Mouse Model[J].PloS One,2012,7(10):e47115.
[14]ABDOU AG,ABD-ELWAHED M,BADR M,et al.The differential Immunoh-istochemical Expression of p53、cJun,c-Myc and p21 Between HCV-re-lated Hepatocellular Carcinoma With and Without Cirrhosis[J].Appl Im-munohistochem Mol Morphol,2016,24(2):75-87.
[15]KARIMIAN A,AHMADI Y,YOUSEFI B.Multiple function of p21in cell cycle,apoptosis and transcriptional regulation after DNA dama-ge[J].DNA Repair,2016(42):63-71.
[16]李向荣,林星余,肖忠秀,等.p21结构功能与研究新进展[J].医学综述,2008,14(14):2094-2097.
[17]HUANG J,YANG G,HUANG Y,et al.1,25(OH)2D3inhibits the progre-ssion of hepatocellular carcinoma via down-regulating HDAC2and up-r-egulating P21(WAFI/CIP1)[J].Mol Med Rep,2016,13(2):1373-1380.
[2]阿尤甫江·阿布都热依木,斯坎德尔·白克力,王延娇,等.HPAA组织结构和功能的变化在异常黑胆质型肝癌病证模型中的作用研究[J].新疆医科大学学报,2015,38(3):273-277.
[3]玉素甫·吐尔逊,斯坎德尔·白克力,哈木拉提·吾甫尔,等.异常黑胆质性肝癌病证模型肝硬化期的肝脏形态学研究[J].科技导报,2010,28(24):82-88.
[4]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.
[5]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.
[6]王延蛟,热沙来提·阿不都瓦衣特,哈木拉提·吾甫尔,等.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[J].科技导报,2015,33(11):84-89.
[7]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,02130082.8[P].2003-04-06.
[8]KIM S,AN SS.Role of p53isoforms and aggregations in cancer[J].Medicine,2016,95(26):e3993.
[9]KASTAN MB.Commentary on participation of p53protein in cellular response to DNA damage[J].Cancer Res,2016,76(13):3663-3665.
[10]张潇荟,姜英,杨军.p53非依赖性信号通路在DNA损伤致细胞凋亡中的研究进展[J].浙江大学学报,2013,42(2):217-223.
[11]王娅杰,孙华,刘耕陶,等.p53在DNA损伤反应中的研究进展[J].药学学报,2011,46(12):1413-1419.
[12]李哲夫,宋敏,王一,等.肝癌组织中HBsAg、PCNA、p53及p21表达的意义[J].中国普通外科杂志,2013,12(3):215-216.
[13]CHENG M,HE B,WAN T,et al.5-Fluorouracil Nanoparticles Inhibit Hepatocellular Carcinoma via Activation of the p53Pathway in the O-rthotopic Transplant Mouse Model[J].PloS One,2012,7(10):e47115.
[14]ABDOU AG,ABD-ELWAHED M,BADR M,et al.The differential Immunoh-istochemical Expression of p53、cJun,c-Myc and p21 Between HCV-re-lated Hepatocellular Carcinoma With and Without Cirrhosis[J].Appl Im-munohistochem Mol Morphol,2016,24(2):75-87.
[15]KARIMIAN A,AHMADI Y,YOUSEFI B.Multiple function of p21in cell cycle,apoptosis and transcriptional regulation after DNA dama-ge[J].DNA Repair,2016(42):63-71.
[16]李向荣,林星余,肖忠秀,等.p21结构功能与研究新进展[J].医学综述,2008,14(14):2094-2097.
[17]HUANG J,YANG G,HUANG Y,et al.1,25(OH)2D3inhibits the progre-ssion of hepatocellular carcinoma via down-regulating HDAC2and up-r-egulating P21(WAFI/CIP1)[J].Mol Med Rep,2016,13(2):1373-1380.