[1]边 倩,曹 妮,刘 航,等.益脾养肝方对大鼠肝癌癌前病变miR-221表达的影响*[J].陕西中医,2020,(11):1515-1519.[doi:DOI:10.3969/j.issn.1000-7369.2020.11.001]
 BIAN Qian,CAO Ni,LIU Hang,et al.Effect of Yipi Yanggan decoction on miR-221 expression in rats with hepatic precancerous lesions[J].,2020,(11):1515-1519.[doi:DOI:10.3969/j.issn.1000-7369.2020.11.001]
点击复制

益脾养肝方对大鼠肝癌癌前病变miR-221表达的影响*
分享到:

《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2020年11期
页码:
1515-1519
栏目:
基础研究
出版日期:
2020-11-05

文章信息/Info

Title:
Effect of Yipi Yanggan decoction on miR-221 expression in rats with hepatic precancerous lesions
作者:
边 倩1曹 妮2刘 航1 李京涛1 魏海梁1闫曙光1 郭英君3△
1.陕西中医药大学附属医院(咸阳 712021); 2.陕西中医药大学(咸阳 712046); 3.宁夏回族自治区人民医院(银川 750001)
Author(s):
BIAN QianCAO NiLIU Hanget al.
Affiliated Hospital of Shaanxi University of Chinese Medicine(Xianyang 712021)
关键词:
miR-221 益脾养肝方 护肝片 肝细胞凋亡 肝癌癌前病变模型 大鼠
Keywords:
miR-221 Yipi Yanggan recipe Hugan tablet Hepatocyte apoptosis Precancerous lesion model of liver cancer Rats
分类号:
R735.7
DOI:
DOI:10.3969/j.issn.1000-7369.2020.11.001
文献标志码:
A
摘要:
目的:探讨益脾养肝方对二乙基亚硝胺诱导大鼠肝癌癌前病变的疗效和对肝细胞中miR-221表达的影响。方法:取180只大鼠随机分为空白组、模型组、护肝片组及益脾养肝方低、中、高剂量组,每组30只。除空白组外,其余各组大鼠构建肝癌癌前病变模型,建模成功后,护肝片组行1 g/ml剂量灌胃治疗,益脾养肝方低、中、高剂量组分别行不同剂量(0.3、0.6、1.2 g/ml)灌胃治疗,空白组和模型组灌胃同等体积生理盐水。采用苏木精-伊红(HE)染色法观察各组肝组织形态变化,免疫荧光染色法检测肝细胞凋亡情况,qRT-PCR法检测肝组织miR-221表达水平。结果:与空白组大鼠比较,其余建模各组大鼠毛色晦暗,动作反应迟缓,益脾养肝方高剂量组和护肝片组上述症状有所改善,模型组和益脾养肝方低剂量组大鼠各死亡1只。HE染色结果显示,与空白组比较,其余建模各组肝组织结构均受到破坏,异型性增生细胞紧密排列,肝细胞胞质水肿。六组肝细胞凋亡阳性细胞数比较,差异具有统计学意义(P<0.05); 与护肝片组比较,益脾养肝方低、中剂量组均升高(P<0.05); 益脾养肝方各剂量组之间比较,益脾养肝方高剂量组均低于低、中剂量组(P<0.05),且益脾养肝方中剂量组低于低剂量组(P<0.05)。六组肝组织miR-221相对表达量比较,差异具有统计学意义(P<0.05); 与护肝片组比较,益脾养肝方低、中、高剂量组均升高(P<0.05); 益脾养肝方各剂量组之间比较,益脾养肝方高剂量组均低于低、中剂量组(P<0.05),且益脾养肝方中剂量组低于低剂量组(P<0.05)。结论:益脾养肝方能够改善肝脏功能,延缓肝癌癌前病变进展,其治疗机制可能与抑制miR-221表达作用有关。
Abstract:
Objective:To investigate the therapeutic effect of Yipi Yanggan decoction on precancerous lesion of liver cancer induced by diethylnitrosamine and the expression of miR-221 in liver cells.Methods:The total of 180 rats were randomly divided into blank group,model group,Hugan tablet group and Yipi Yanggan decoction low,medium and high dose groups,30 rats in each group.In addition to the blank group,the rats in other groups were established with precancerous lesion model of liver cancer.After successful modeling,Hugan tablet group was treated with 1 g/ml dose by gavage,the low,medium,and high dose Yipi Yanggan decoction groups were given different doses(0.3,0.6,1.2 g/ml)respectively,and the blank group and model group were given the same volume of normal saline.The morphological changes of liver tissue were observed by Hematoxylin-Eosin(HE)staining,hepatocyte apoptosis was detected by immunofluorescence staining,and miR-221 expression was detected by qRT-PCR.Results:Compared with the blank group,rats in other modeling groups had dark hair color and slow action response.The above symptoms were improved in high dose Yipi Yanggan decoction group and Hugan tablet group.One rat died in the model group and the low dose Yipi Yanggan decoction group.The results of HE staining showed that compared with the blank group,the structure of liver tissue in other modeling groups was damaged,the dysplastic cells were closely arranged,and the cytoplasmic edema of hepatocytes was observed.Compared with the model group,the number of hepatocyte apoptosis positive cells in Hugan tablet group and Yipi Yanggan decoction middle and high dose groups were decreased(P<0.05); compared with Hugan tablet group,the low and medium dose Yipi Yanggan decoction groups were increased(P<0.05); the Yipi Yanggan decoction groups were significantly higher than those of each dose group.Compared with the low and medium dose groups,the Yipi Yanggan decoction high dose group was lower than the low dose and medium dose groups(P<0.05),and the Yipi Yanggan decoction middle dose group was lower than the low-dose group(P<0.05).Compared with the blank group,the relative expression of miR-221 in the liver tissue of the six groups was significantly different(P<0.05); and compared with Hugan tablet group,the Yipi Yanggan decoction low,medium and high dose groups were increased(P<0.05); Yipi Yanggan decoction group were increased(P<0.05).Compared with the low and medium dose groups,the Yipi Yanggan decoction high-dose group was lower than the low-dose and medium-dose groups(P<0.05),and the Yipi Yanggan decoction middle dose group was lower than the low-dose group(P<0.05).Conclusion:Yipi Yanggan decoction can improve liver function and delay the progression of precancerous lesions of liver cancer.Its therapeutic mechanism may be related to the inhibition of miR-221 expression.

参考文献/References:

1] 中国抗癌协会肝癌专业委员会,中华医学会肝病学分会肝癌学组,中国抗癌协会病理专业委员会,等.原发性肝癌规范化病理诊断指南(2015年版)[J].中华肝胆外科杂志,2015,21(3):145-151.
[2] Wang RH,He LY,Zhou SH.The role of gene sculptor microRNAs in human precancerous lesions[J].Onco Targets Ther,2018,11(9):5667-5675.
[3] 张海雄,彭 亮,冯伟清.原发性肝细胞癌组织miR-221表达变化及其对肿瘤侵袭和转移的影响[J].山东医药,2019,59(19):14-17,34.
[4] 李京涛,郭 师,席 奇,等.益脾养肝方联合肝动脉化疗栓塞术治疗原发性肝癌的疗效观察[J].陕西中医,2017,38(8):944-945.
[5] 何玲玲,赵亚林,杜林林,等.肝结节性病变的病理和影像学表现[J].临床肝胆病杂志,2018,31(9):1547-1550.
[6] 周 燕.原发性肝癌中医证型与血清肿瘤标志物关系分析[J].光明中医,2019,34(8):1145-1147.
[7] 刘亚珠,李京涛,魏海梁,等.益脾养肝方对大鼠肝癌癌前病变组织PCNA、GGT蛋白表达的影响[J].陕西中医,2017,38(2):264-266.
[8] 李福广,徐 军.姜黄素对原发性肝癌组织中肝星状细胞活性影响的实验研究[J].陕西医学杂志,2016,45(6):649-651,712.
[9] Brian K,Cheow P,Lim T,et al.Circulating microRNAs as potential diagnostic and prognostic biomarkers in hepatocellular carcinoma[J].Scientific Reports,2019,9(1):45-48.
[10] Pineau P,Volinia S,McJunkin K,et al.MiR-221 overexpression contributes to liver tumorigenesis[J].Proc Natl Acad Sci USA,2018,107(11):264-269.
[11] Liu Z,Wang C,Jiao X,et al.MiR-221 promotes growth and invasion of hepatocellular carcinoma cells by constitutive activation of NF-κB[J].Am J Transl Res,2018,8(11):4764-4777.
[12] Bae H,Kim H,Park S,et al.MicroRNA-221 governs tumor suppressor HDAC6 to potentiate malignant progression of liver cancer[J].Journal of Hepatology,2018,63(2):408-419.
[13] 李京涛,闫曙光,魏海梁,等.益脾养肝方对大鼠肝癌癌前病变NF-κB、STAT3蛋白表达的影响[J].辽宁中医杂志,2018,45(1):196-198,231.
[14] Li T,Li M,Hu S,et al.MiR-221 mediates the epithelial-mesenchymal transition of hepatocellular carcinoma by targeting AdipoR1[J].International Journal of Biological Macromolecules,2017,41(81):30-33.
[15] Fu Y,Liu M,Li F,et al.MiR-221 promotes hepatocellular carcinoma cells migration via targeting PHF2[J].Biomed Res Int,2019,43(71):405.

备注/Memo

备注/Memo:
*国家自然科学基金资助项目(81603612);陕西省科技厅科研基金资助项目(2016SF-234,2018KJXX-093);宁夏回族自治区自然科学基金资助项目(NZ17278);陕西中医药大学学科创新团队建设项目(2019-YL05)
更新日期/Last Update: 2020-11-09