大黄蛰虫丸联合TACE术对原发性肝癌患者(瘀血阻络型)VEGF,MMP-2,TGF-β1及免疫功能的影响Effect of Dahuang Zhechong Pills combined with TACE on VEGF, MMP-2, TGF-β1 and immune function of patients with primary liver cancer (blood stasis and collaterals blocking type)
戴朝明;靳松;张济周;
DAI Chao-ming;JIN Song;ZHANG Ji-zhou;Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University;
摘要(Abstract):
探讨大黄蛰虫丸联合肝动脉化疗栓塞术(hepatic artery chemoembolization,TACE术)治疗对原发性肝癌患者(瘀血阻络型)肿瘤指标及免疫功能的影响,观察其在此类患者治疗中的应用价值,旨在为该病提供有效的治疗手段。将2019年6月至2019年12月因原发性肝癌患者(瘀血阻络型)于温州市中医院就诊的79例纳入研究,纳入研究前均用随机数字表法对患者进行分组。对照组40例患者单纯采用TACE术,观察组39例患者联合大黄蛰虫丸口服治疗,治疗4周后比较疗效。结果治疗后观察组血清CD4~+细胞、CD4~+/CD8~+、CD3~+细胞等免疫功能指标均大于对照组,差异有统计学意义(P<0.05);观察组血清甲胎蛋白(alpha-fetoprotein,AFP)、糖类抗原199(carbohydrate antigen 199,CA199)等肿瘤指标,谷丙转氨酶(glutamic-pyruvic transaminase,ALT)、总胆红素(total bilirubin,TBiL)水平低于对照组,差异有统计学意义(P<0.05);观察组血浆血管内皮生长因子(vascular endothelial growth factor,VEGF)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)、基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)水平低于对照组,差异有统计学意义(P<0.05);观察组总有效率87.18%,获益率94.87%,对照组总有效率67.50%,获益率85.00%,观察组总有效率高于对照组(P<0.05);观察组骨髓抑制、胃肠道反应、发热、肾功能损伤、周围神经损伤等不良反应总发生率48.72%,低于对照组的82.50%,差异有统计学意义(P<0.05)。结果表明,对于原发性肝癌患者(瘀血阻络型),采用大黄蛰虫丸联合TACE术治疗有重要意义,有助于提高免疫力,保护肝功能,降低转移风险,降低化疗不良反应发生,值得推广。
To investigate the effects of Dahuang Zhechong Pills combined with hepatic arterial chemoembolization(TACE) on tumor index and immune function of patients with primary liver cancer(blood stasis and collaterals blocking type), observe its application values in treatment of such patients, and provide effective treatment means for this disease. From June 2019 to December 2019, 79 patients with confirmed primary liver cancer(blood stasis and collaterals blocking type) treated in Wenzhou Hospital of Traditional Chinese Medicine were included in this study, all of which were grouped with random number table method before inclusion in this study. 40 patients in the control group were treated with TACE, while 39 patients in the observation group were treated with Dahuang Zhechong Pills combined with TACE. The efficacy was compared between two groups after 4 weeks of treatment. The immune function indexes of serum CD4~+ cells, CD4~+/CD8~+, CD3~+ cells of the observation group were higher than those in control group after treatment(P<0.05), and tumor indexes such as serum alpha-fetoprotein(AFP), carbohydrate antigen 199(CA199) and glutamic-pyruvic transaminase(ALT), total bilirubin(TBiL) levels were lower than those in the control group, with statistically significant differences(P<0.05). Plasma vascular endothelial growth factor(VEGF), transforming growth factor-β1(TGF-β1), and matrix metalloprotei-nase-2(MMP-2) levels in the observation group were lower than those in the control group after treatment, with statistically significant differences(P<0.05). The total effective rate of the observation group was 87.18%, higher than 67.50% in the control group, and the benefit rate was 94.87% in the observation group, higher than 85.00% in the control group(P<0.05). The total incidence of adverse reactions such as bone marrow suppression, gastrointestinal reaction, fever, renal function injury and peripheral nerve injury in the observation group was 48.72%, lower than 82.50% in the control group, with statistically significant difference(P<0.05). In summary, the combination of Dahuang Zhechong Pills with TACE could improve immunity, protect liver function, and reduce the risk of metastasis and the incidence of adverse reactions from chemotherapy, so it is worth popularizing for patients with primary liver cancer(blood stasis and collaterals blocking type).
关键词(KeyWords):
大黄蛰虫丸;肝动脉化疗栓塞术;原发性肝癌;瘀血阻络型;MMP-9;VEGF;TGF-β1;免疫功能
Dahuang Zhechong Pills;hepatic artery chemoembolization;primary liver cancer;blood stasis and collaterals blocking type;MMP-9;VEGF;TGF-β1;immune function
基金项目(Foundation): 温州市科技局基础性医疗卫生科技项目(2019Y0979)
作者(Author):
戴朝明;靳松;张济周;
DAI Chao-ming;JIN Song;ZHANG Ji-zhou;Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University;
Email:
DOI: 10.19540/j.cnki.cjcmm.20200716.501
参考文献(References):
- [1] 曹学冬,孙明瑜,张海阳,等.原发性肝癌的分子发病机制研究进展[J].肝胆外科杂志,2019,27(2):153.
- [2] 张爽,王锋,孟庆玲,等.原发性肝癌患者流行病学与乙型肝炎病毒感染调查[J].中国疫苗和免疫,2018,24(2):133.
- [3] 钱程.MicroRNA-126在肝细胞肝癌发生发展及新生血管生成中的作用机制[J].山东医学高等专科学校学报,2019,41(6):445.
- [4] 代想成,周园红,周晓琳,等.肝动脉化疗栓塞术联合复方斑蝥治疗中晚期原发性肝癌疗效和安全性的Meta分析[J].海南医学,2017,28(21):3576.
- [5] 周文超,蔡祥胜,熊小敏,等.CD4+CD25+CD127low调节性T细胞在原发性肝癌患者外周血的表达及临床意义[J].国际检验医学杂志,2020,41(4):403.
- [6] 廖桂雅.原发性肝癌病因与中医证型分析探讨[D].广州:广州中医药大学,2008.
- [7] 原发性肝癌诊疗规范(2019年版)[J].中国实用外科杂志,2020,40(2):121.
- [8] 郑筱萸.中药新药临床指导原则[M].北京:中国医药科技出版社,2002:162.
- [9] 谭炜,朱锦德,郭敬强,等.经动脉化疗栓塞联合高强度聚焦超声治疗高龄原发性肝癌的临床研究[J].中西医结合肝病杂志,2017,27(6):346.
- [10] 张维晴,肖祖林,吴驻林,等.中药外敷联合三阶梯止痛法治疗原发性肝癌疼痛的系统评价[J].中国中药杂志,2019,44(9):1938.
- [11] CHEN Q W,CHENG C S,CHEN H,et al.Effectiveness and complications of ultrasound guided fine needle aspiration for primary liver cancer in a Chinese population with serum α-fetoprotein levels≤200 ng/mL--a study based on 4 312 patients[J].PLoS ONE,2014,9(8):101.
- [12] 周彬,陆惠波,侯凯哲.血清甲胎蛋白、甲胎蛋白异质体与肝癌患者的近期疗效和预后的关系及其诊断价值分析[J].国际消化病杂志,2020,40(1):63.
- [13] 李国华.血清AFP,CA125,CA153,CA199联合检测对肝癌的诊断价值分析[J].临床检验杂志(电子版),2020,9(1):23.
- [14] 杨丽.化学发光免疫法检测肿瘤标志物CA199及AFP对原发性肝癌的诊断价值[J].承德医学院学报,2019,36(5):425.
- [15] 沈学文,刘爱,邬艳,等.联合检测外周血VEGF和EMMPRIN mRNA在肝癌转移监测中的意义[J].实验与检验医学,2019,37(6):1019.
- [16] 琚安栋,赵宏峰,岳爱民,等.微波消融治疗兔VX2肝癌外周血白介素-2的变化[J].临床医药文献电子杂志,2017,4(19):3568.
- [17] 张景洲,冯相伟,孟繁平.扶正解毒通络方对人肝癌HepG2细胞MMP-2,MMP-9表达及细胞侵袭作用的影响[J].中国免疫学杂志,2017,33(4):542.
- [18] 李威威.外周血MMP-2和MMP-7水平与原发性肝癌患者预后的相关性[J].中国卫生工程学,2019,18(6):894.
- [19] 张淑群,张莹,杨鑫,等.EZH2,MMP-2及MMP-9在肝癌侵袭转移中的作用及关系[J].西安交通大学学报(医学版),2019,40(6):947.
- [20] 吕美娴,廖智红,周欢,等.裂果薯皂苷单体Ⅰ通过TGF-β1调控上皮间质转化对人肝癌细胞SMMC-7721侵袭和转移的影响[J].中国药理学通报,2020,7(3):408.
- [21] 连文萍,李砺锋,别良玉,等.血清TGFβ1,sIL-2R,GP73,AFP及CEA在肝癌放射治疗前后的变化及意义[J].中国现代普通外科进展,2019,22(9):732.
- [22] 金向宇,李晖.老年肝癌患者血清TGF-β1,Smad4水平及临床意义[J].中国老年学杂志,2019,39(11):2655.
- [23] SEKI T,TAMAI T,NAKAGAWA T,et al.Combination therapy with transcatheter arterial chemoembolization and percutaneous microwave coagulation therapy for hepatocellular carcinoma[J].Cancer,2015,89(6):1245.
- [24] 丁梦梦,高沿航.免疫治疗在肝细胞癌辅助治疗中的应用[J].肝脏,2019,24 (12):1377.
- [25] 赵士冲,谢长远,姚平刚.复方斑蝥胶囊对原发性肝癌介入治疗后细胞免疫功能的效果及机制[J].中华中医药学刊,2019,37(11):2785.
- [26] 张容容,邵明义,符宇,等.槐耳颗粒辅助治疗原发性肝癌的系统评价[J].中国中药杂志,2021,46(2):478.
- [27] 童洪亮.大黄蛰虫丸联合化疗治疗晚期胃癌临床观察[J].河南医学研究,2016,25 (7):1289.
- [28] 孙鹏.大黄蛰虫丸配合化疗治疗胰腺癌血瘀证的临床研究[J].现代诊断与治疗,2014,25(21):4872.
- [29] 张希琼.大黄蛰虫丸抗肝癌活性成分筛选及其药动学研究[D].南京:南京中医药大学,2019.
- [30] 张云.大黄蛰虫丸的抑瘤作用及对荷瘤小鼠外周血TNF-α、IL-4含量的影响[D].沈阳:辽宁中医药大学,2012.
- [31] 曹慧慧.大黄蛰虫丸对Lewis肺癌荷瘤小鼠免疫状态干预作用的实验研究[D].太原:山西中医学院,2015.
- [32] 张宇,陈华国,赵超,等.中药有效成分抗肝癌作用机制研究进展[J].中国中药杂志,2020,45(14):3395
- [33] 徐菲,曾杨丽,李娟,等.中药复方防治肝癌作用机制研究进展[J].中国实验方剂学杂志,2019,25(24):196.
- 大黄蛰虫丸
- 肝动脉化疗栓塞术
- 原发性肝癌
- 瘀血阻络型
- MMP-9
- VEGF
- TGF-β1
- 免疫功能
Dahuang Zhechong Pills - hepatic artery chemoembolization
- primary liver cancer
- blood stasis and collaterals blocking type
- MMP-9
- VEGF
- TGF-β1
- immune function
- 戴朝明
- 靳松
- 张济周
DAI Chao-ming- JIN Song
- ZHANG Ji-zhou
- Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University
- 戴朝明
- 靳松
- 张济周
DAI Chao-ming- JIN Song
- ZHANG Ji-zhou
- Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University