葛根芩连汤治疗湿热瘀毒型肝细胞癌TACE术后栓塞综合征的临床观察

周玟; 申书华; 程晔; 李伟兵; 余雅素; 陈妍

doi:10.14148/j.issn.1672-0482.2022.0397

葛根芩连汤治疗湿热瘀毒型肝细胞癌TACE术后栓塞综合征的临床观察

doi: 10.14148/j.issn.1672-0482.2022.0397

周玟^{1, 2,},
申书华¹,
程晔¹,
李伟兵¹,
余雅素¹,
陈妍^1, ,

1.
江苏省肿瘤医院中西医结合科, 江苏南京 210009
2.
南京中医药大学中医学院 · 中西医结合学院, 江苏南京 210023

基金项目:

国家自然科学基金面上项目 81874452

江苏省肿瘤医院院内课题面上项目 ZM201810

详细信息

作者简介:
周玟, 女, 主治中医师, E-mail: av99175@163.com

通讯作者:
陈妍, 女, 主任中医师, 主要从事中西医结合防治恶性肿瘤及其并发症的研究, E-mail: amandacy@163.com

中图分类号: R273
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- 被引次数: 0
出版历程
- 收稿日期: 2022-02-13
- 发布日期: 2022-05-10

Clinical Observation of Gegen Qinlian Decoction for Post-TACE Embolization Syndrome in Hepatocellular Carcinoma Patients with the Syndrome of Damp-Heat and Stasis-Toxin

ZHOU Min^{1, 2
,},
SHEN Shu-hua¹,
CHENG Ye¹,
LI Wei-bing¹,
YU Ya-su¹,
CHEN Yan^{1
, ,}

1.
Department of Integrated Traditional and Western Medicine, Jiangsu Cancer Hospital, Nanjing 210009, China
2.
School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China

摘要

摘要: 目的观察葛根芩连汤对湿热瘀毒型肝细胞癌(Hepatocellular carcinoma, HCC)患者经导管肝动脉栓塞化疗(Transcatheter hepatic arterial chemoembolization, TACE)术后栓塞综合征的疗效。方法选取2019年1月至2021年12月江苏省肿瘤医院100例湿热瘀毒型HCC门诊及住院患者, 随机分为对照组50例、治疗组50例(脱落3例), 2组均接受TACE治疗, 术后对照组予常规西药对症治疗, 治疗组在对照组治疗基础上予葛根芩连汤颗粒剂口服治疗, 2组疗程均为2周。记录2组患者治疗期间出现TACE术后栓塞综合征主要症状的分级情况及持续时间, 评估2组患者治疗前后中医证候积分变化情况, 检测2组患者治疗前后肝功能指标[丙氨酸氨基转移酶(Alanine aminotransferase, ALT)、天门冬氨酸氨基转移酶(Aspartate aminotransferase, AST)、总胆红素(Total bilirubin, TB)、γ-谷氨酰转肽酶(Gamma-glutamyl transpeptidase, GGT)]、脂质代谢相关指标[总胆固醇(Total cholesterol, TC)、甘油三酯(Triglyceride, TG)、低密度脂蛋白胆固醇(Low density lipoprotein cholesterol, LDL-C)、高密度脂蛋白胆固醇(High density lipoprotein cholesterol, HDL-C)]及免疫指标(CD4⁺、CD8⁺、调节性T细胞相对比例及CD4⁺/CD8⁺)表达水平, 并进行发病因素相关分析。结果治疗期间, 治疗组患者的发热和恶心呕吐严重程度较对照组减轻(P < 0.05), 主要症状持续时间较对照组缩短(P < 0.05)。治疗后, 2组患者中医证候均显著改善(P < 0.01), 治疗组发热、恶心呕吐、纳差、总积分改善情况优于对照组(P < 0.05, P < 0.01), 治疗组中医证候疗效优于对照组(P < 0.05);2组患者肝功能、脂质代谢及免疫相关指标均较治疗前改善(P < 0.05, P < 0.01), 治疗组血清ALT、TB、TC、TG、LDL-C水平改善优于对照组(P < 0.05, P < 0.01), 治疗组外周血CD4⁺、调节性T细胞相对比例及CD4⁺/CD8⁺低于对照组(P < 0.05, P < 0.01)。TG、LDL-C、TB、ALT水平、调节性T细胞比例均是发生Ⅲ~Ⅳ级栓塞综合征主要症状的危险因素(P < 0.05, P < 0.01)。结论葛根芩连汤对湿热瘀毒型HCC患者TACE术后栓塞综合征有一定的疗效。
- 葛根芩连汤 /
- 湿热瘀毒型 /
- 肝细胞癌 /
- 栓塞综合征
Abstract: OBJECTIVE To observe the efficacy of Gegen Qinlian Decoction on embolization syndrome after transcatheter hepatic arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with the syndrome of damp-heat and stasis-toxin. METHODS From January 2019 to December 2021, a total of 100 HCC patients with the syndrome of damp-heat and stasis-toxin in Jiangsu Cancer Hospital were selected and randomly divided into 50 cases in the control group and 50 cases in the treatment group (with 3 cases dropped out). Both groups received TACE treatment, and the control group was treated with conventional western medicine after surgery, while the treatment group was given with Gegen Qinlian Decoction granules based on the treatment in the control group. The course of treatment in both groups was two weeks. The gradation and duration of the main symptoms of post-TACE embolism syndrome were recorded during the treatment period. In addition, the changes in the traditional Chinese medicine (TCM) syndrome score were assessed before and after the treatment. Besides, we measured the liver function indicators [Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Total bilirubin (TB), Gamma-glutamyl transpeptidase (GGT)], lipid metabolism related indexes [Total cholesterol (TC), Triglyceride (TG), Low density lipoprotein cholesterol (LDL-C), High density lipoprotein cholesterol (HDL-C)], as well as the expression levels of immune indexes (relative ratio of CD4⁺, CD8⁺, regulatory T cells and CD4⁺/CD8⁺), and also performed the morbidity factor correlation analysis. RESULTS Within two weeks of treatment, patients in the treatment group had less severe fever, nausea, and vomiting than those in the control group (P < 0.05), and the duration of major symptoms was shorter than that in the control group (P < 0.05). After treatment, the TCM syndromes in both groups alleviated significantly (P < 0.01), but the treatment group had better improvement in fever, nausea, vomiting, poor appetite, and total score than the control group (P < 0.05, P < 0.01). Thus, the efficacy of TCM syndromes was better in the treatment group than in the control group (P < 0.05). On top of that, the liver function, lipid metabolism, and immune-related indexes showed better results in both groups than before treatment (P < 0.05, P < 0.01), while the results relevant to serum ALT, TB, TC, TG and LDL-C were better in the treatment group than in the control group (P < 0.05, P < 0.01). Moreover, the expression levels of peripheral blood CD4⁺, regulatory T cells, as well as CD4⁺/CD8⁺ in the treatment group were lower than those in the control group (P < 0.05, P < 0.01). It is worth noting that TG, LDL-C, TB, ALT levels, and regulatory T-cell ratio were risk factors for the development of major symptoms of III-Ⅳ embolic syndrome (P < 0.05, P < 0.01). CONCLUSION Gegen Qinlian Decoction is effective in post-TACE embolization syndrome in HCC patients with the syndrome of damp-heat and stasis-toxin.
- Gegen Qinlian Decoction /
- syndrome of damp-heat and stasis-toxin /
- hepatocellular carcinoma /
- embolization syndrome

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表 1 2组患者治疗期间栓塞综合征主要症状严重程度分级情况比较

Table 1. Comparison of the grading of the primary symptoms of embolism syndrome in the two groups during the period of treatment

组别	例数	发热					恶心呕吐					疼痛
组别	例数	0	Ⅰ	Ⅱ	Ⅲ	Ⅳ	0	Ⅰ	Ⅱ	Ⅲ	Ⅳ	0	Ⅰ	Ⅱ	Ⅲ	Ⅳ
治疗组	47	3	25	15	2	2	2	11	11	14	9	1	12	16	13	5
对照组	50	2	10	23	12	3	0	5	14	18	13	2	4	20	18	6
注: 组间比较, Z_发热=-3.562, P < 0.05;Z_恶心呕吐=-2.182, P < 0.05;Z_疼痛=-1.362, P>0.05。

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表 2 2组患者治疗期间栓塞综合征主要症状持续时间比较(x±s, d)

Table 2. Comparison of duration of main symptoms of embolism syndrome in the two groups (x±s, d)

组别	例数	发热	恶心呕吐	疼痛	腹胀
治疗组	47	1.98±0.97^#	3.23±1.55^#	3.23±1.20^#	4.51±1.93^#
对照组	50	3.20±1.78	5.26±2.21	4.54±2.45	6.72±1.99
注: 组间比较, ^#P < 0.05。

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表 3 2组患者治疗前后中医证候积分比较(x±s)

Table 3. Comparison of TCM symptom scores before and after treatment between the 2 groups (x±s)

组别	时间	例数	发热	恶心呕吐	胁肋疼痛	腹胀	纳差	乏力	总积分
治疗组	治疗前	47	2.77±1.36	3.70±1.56	3.66±1.34	3.32±0.96	4.51±1.14	3.49±1.14	21.28±3.67
	治疗后	47	0.26±0.68^**##	0.55±0.90^**##	1.66±0.88^**	1.28±1.14^**	1.87±1.47^**#	1.96±1.22^**	7.57±3.17^**##
对照组	治疗前	50	2.68±1.32	4.12±1.37	3.92±1.21	2.84±1.41	4.00±1.81	3.52±1.43	21.96±5.26
	治疗后	50	1.56±1.01^**	2.20±1.30^**	2.00±1.07^**	0.96±1.01^**	2.44±1.23^**	2.28±1.51^**	11.44±4.45^**
注: 组内比较, ^{* *}P < 0.01;组间比较, ^#P < 0.05, ^##P < 0.01。

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表 4 2组患者中医证候积分临床疗效比较

Table 4. Comparison of efficacy for TCM syndrome in the two groups

组别	例数	显著改善	部分改善	无改善	总改善率/%
治疗组	47	12	29	6	87.20^#
对照组	50	8	26	16	68.00
注: 组间比较, χ²=5.11, ^#P < 0.05。

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表 5 2组患者治疗前后肝功能指标比较(x±s)

Table 5. Comparison of liver function indicators between the two groups before and after treatment (x±s)

组别	时间	例数	ALT/(U·L^-1)	AST/(U·L^-1)	TB/(μmol·L^-1)	GGT/(U·L^-1)
治疗组	治疗前	47	86.30±17.30	93.38±40.33	33.97±7.89	220.09±132.81
	治疗后	47	47.28±18.45^**##	54.55±27.41^**	16.53±4.95^**##	165.60±93.91^*
对照组	治疗前	50	87.02±16.78	92.28±36.68	33.79±7.32	226.16±130.11
	治疗后	50	57.94±15.38^**	61.12±23.33^**	20.35±4.86^**	178.42±102.22^*
注: 组内比较, ^P < 0.05, ^{ *}P < 0.01;组间比较, ^##P < 0.01。

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表 6 2组患者治疗前后脂质代谢指标比较(x±s, mmol · L^-1)

Table 6. Comparison of lipid metabolism related indicators between the two groups before and after treatment (x±s, mmol · L^-1)

组别	时间	例数	TC	TG	HDL-C	LDL-C
治疗组	治疗前	47	4.38±1.06	1.68±0.80	1.20±0.41	2.78±1.08
	治疗后	47	3.54±0.56^**##	1.10±0.55^**#	1.49±0.41^**	2.18±0.77^**##
对照组	治疗前	50	4.41±1.07	1.70±0.89	1.19±0.42	3.02±0.79
	治疗后	50	3.99±0.84^*	1.42±0.74^*	1.48±0.40^**	2.62±0.69^**
注: 组内比较, ^P < 0.05, ^{ *}P < 0.01;组间比较, ^#P < 0.05, ^##P < 0.01。

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表 7 2组患者治疗前后免疫功能指标比较(x±s)

Table 7. Comparison of immune related indicators between the two groups before and after treatment (x±s)

组别	时间	例数	CD4⁺/%	CD8⁺/%	CD4⁺/CD8⁺比值	调节性T细胞/%
治疗组	治疗前	47	44.21±10.54	19.29±5.96	2.65±1.38	9.89±1.90
	治疗后	47	37.58±7.58^**#	26.78±4.27^**#	1.45±0.41^**##	8.01±1.93^**#
对照组	治疗前	50	44.41±9.99	19.11±6.51	2.70±1.36	9.98±1.89
	治疗后	50	41.36±8.43^**	24.07±6.00^**	1.85±0.65^**	8.88±1.62^**
注: 组内比较, ^{* *}P < 0.01;组间比较, ^#P < 0.05, ^##P < 0.01。

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表 8 发生Ⅲ~Ⅳ级栓塞综合征主要症状相关因素的二分类多元Logistic回归分析

Table 8. Binary multiple Logistic regression analysis of factors related to major symptoms of grade Ⅲ to Ⅳ embolism syndrome

影响因素	系数B	P值	Exp(B)	95%CI
影响因素	系数B	P值	Exp(B)	下限	上限
TG	0.700	0.010	2.013	1.180	3.435
LDL-C	0.585	0.004	1.795	1.202	2.680
调节性T细胞	0.410	0.005	1.506	1.131	2.006
TB	0.101	0.008	1.106	1.027	1.191
ALT	0.041	0.031	1.042	1.004	1.082

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