Advances in Clinical Medicine
Vol.06 No.01(2016), Article ID:16835,7 pages
10.12677/ACM.2016.61001

Clinical Observation of Traditional Chinese Medicine Preparation-Ganbao Particulate Adjuvant Treatment of Young and Middle-Aged Men with Non-Alcoholic Fatty Liver

Hongzan Ji*, Lin Wu#, Xiaowei Wu, Haibin Li, Jianmin Rong, Hui Shi, Lian’e Xu, Jiong Liu, Fangyu Wang

Department of Gastroenterology, Nanjing General Hospital of Nanjing Military Command, PLA, Nanjing Jiangsu

Received: Jan. 5th, 2016; accepted: Jan. 25th, 2016; published: Jan. 28th, 2016

Copyright © 2016 by authors and Hans Publishers Inc.

This work is licensed under the Creative Commons Attribution International License (CC BY).

http://creativecommons.org/licenses/by/4.0/

ABSTRACT

Objective: To compare and observe the clinical effect of the traditional Chinese medicine Ganbao particles combined with Essentiale (polyene phosphatidyl choline) with the clinical effect of single agent Essentiale to treat the non-alcoholic fatty liver. Method: Clinical cases of 152 cases of liver function damage were collected. All of them were in accordance with the diagnostic criteria of non-alcoholic fatty liver disease, and were randomly divided into two groups. The observation group was treated with Ganbao granule and Essentiale capsules. The control group was treated with a single oral Essentiale capsules. Age: the age range of the observation group was 19 to 52 years old (31.61 + 8.52). The age range of the control group was 17 to 51 years old (30.53 + 10.15). Patients in the two groups were all informed about the treatment plan and signed a consent form. Experimental detection indicators of the two groups included TBIL, DBIL, ALT, AST, endotoxin, blood lipids, glycosylated hemoglobin and islet beta cell function (FINS/FBG) and other clinical indicators. Results: In the observation group, the total effective rate was 97.37% (144/152), which was significantly higher than that in the control group (120/152), which was statistically significant (P < 0.01). The therapeutic effect of observation group was 47.37% (72/152), which was significantly higher than that of control group whose treatment effect was 23.68% (36/152) (P > 0.05). The protective improvement of islet beta cell function in the observation group was higher than that in the control group (P < 0.01). Conclusion: The treatment of the combination of Ganbao particles and the polyene phosphatidylcholine not only has a positive effect on the NFLD but also can improve the function of the pancreatic β cell.

Keywords:The Particles of Ganbao, Polyene Phosphatidylcholine, Non-Alcoholic Fatty Liver

肝宝颗粒辅助易善复治疗非酒精性脂肪肝临床疗效观察

季洪赞*,吴琳#,吴晓尉,李海兵,戎建明,施慧,许莲娥,刘炯,汪芳裕

南京军区南京总医院消化内科,江苏 南京

收稿日期:2016年1月5日;录用日期:2016年1月25日;发布日期:2016年1月28日

摘 要

目的:对比观察中药制剂肝宝颗粒联合易善复(多烯磷脂酰胆碱)与单剂易善复治疗非酒精性脂肪肝的临床效果。方法:选取肝功能异常的符合非酒精性脂肪肝诊断的患者152例,随机分成每组152例,观察治疗组和对照治疗组各38例,观察组使用肝宝颗粒与易善复,对照组单剂使用易善复,年龄:观察治疗组与对照治疗组,分别为19岁~52岁(31.61 ± 8.52)和17岁~51岁(30.53 ± 10.15),两组患者均符合2010年非酒精性脂肪性肝病诊疗指南诊断标准, 且对治疗方案知情同意。观察两组患者的肝功能(TBIL、DBIL、ALT、AST)和内毒素、血脂、糖化血红蛋白、胰岛β细胞功能(FINS/FBG)等指标的变化。结果:观察组肝功能总有效率为97.37%(144/152)高于对照组的78.95%(120/152),具有统计学意义(p < 0.01),观察组的显效率为47.37%(72/152),好于对照组的肝功能显效率23.68%(36/152) (p > 0.05),治疗组的胰岛β细胞功能提高好于对照组(p < 0.01)。结论:肝宝颗粒联合多烯磷脂酰胆碱对脂肪肝的治疗既有较好的疗效,又对胰岛β细胞功能产生较好的作用。

关键词 :肝宝颗粒,多烯磷脂酰胆碱,非酒精性脂肪肝

1. 引言

非酒精性脂肪肝(nonalcoholic fatty liver disease, NAFLD)是较为常见的现代疾病,脂肪代谢异常成为多种疾病发生和演变的病理因素 [1] ,临床症状表现为疲劳、恶心、呕吐和不同程度的黄疸,本研究自2010年06月至2012年6月,运用中药制剂肝宝颗粒(Ganbao, GB)联合多烯磷脂酰胆碱(Polyene phosphatidy choline capsul, PPCC)治疗非酒精性脂肪肝,疗效满意,现介绍如下:

2. 临床资料

2.1. 诊断标准

符合2010年修订版非酒精性脂肪性肝病诊疗指南临床诊断标准 [2] :1)肝脏影像学表现符合弥漫性脂肪肝的诊断标准且无其他原因可供解释;和(或)2)有代谢综合征相关组分的患者出现不明原因的血清ALT和(或)AST、GGT持续增高半年以上。减肥和改善胰岛素抵抗(IR)后,异常酶谱和影像学脂肪肝改善甚至恢复正常者可明确NAFLD的诊断,临床指标:a) 有不同程度的乏力,食欲不振,肝区胀闷或隐痛,或无症状,或肝、脾大。b) B超检查显示:脂肪肝,肝内血管显示不清晰或纤细,肝后缘回声衰减。或CT检查示:肝密度普遍降低。c) 总胆固醇(TC) ≥ 6.18 mmol /L,甘油三酯(TG) ≥ 2.3 mmol/L。d) 肝功能异常:丙氨酸氨基转移酶(ALT)、γ-谷氨酰转肽酶(γ-GT)升高,患者知情同意,能积极配合治疗方案。排除标准:营养不良、妊娠所致脂肪肝;不愿配合,饮食控制和治疗依从性差;出现药物不良反应未能坚持全疗程。

2.2. 观察指标

随机选择我院消化科门诊自2012年6月至2015年11月收集符合非酒精性脂肪性肝病诊断的152例病例,且所有人选者对治疗方案知情同意,分为观察治疗组与对照治疗组各38例,其中观察组男32例,女6例,对照组男33例,女5例(p > 0.05),两组年龄分别为17~49岁(31.61 ± 8.52)、19~52岁(30.52 ± 10.16) (p > 0.05),病程分别为11.95 ± 2.9(月)和12.63 ± 5.60(月)(p > 0.05),显示两组年龄、性别、病程的可比性,观察两组治疗前后体重指数(BMI)、总胆红素(TBIL)、直接胆红素(DBIL)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、内毒素(Endotoxin,EN)、C肽(C-P),C肽、空腹胰岛素(FINS)、空腹血糖(FBG)、糖化血红蛋白(HbA 1c )、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG),采用美国BECKMANCOULTER公司LX20生化仪检查生化指标,HbA 1c 采用免疫凝集抑制法(DCA2000仪,Bayer公司),C-P采用放射免疫测定法,TC、TG、HDL-C采用脂酶法,FBG以葡萄糖氧化酶法测定、FINS以RIA法测定、β细胞功能按FINS、FBG比值计算、血脂代谢用TC/HDL-C表示 [3] 。

2.3. 治疗方法

2.3.1. 基本治疗

所有患者均接受基本治疗,包括1) 改变饮食习惯,控制总热量,摄入丰富的维生素及矿物质和膳食纤维,减少脂肪和胆固醇的摄入;2) 加强运动,树立健康生活的理念,控制体重,纠正不良行为。

2.3.2. 分组治疗

入组152例,按序数分为观察组与对照组,每组均为76例,观察组即肝宝颗粒联合多烯磷脂酰胆碱胶囊,19~52岁,平均(30.52 ± 10.16)岁,GB(由柴胡、丹参、枸杞子、虎杖、黄芩瓜蒌、升麻、蒲公英等药物组成,南京军区南京总医院生产),每次10 g/袋,1日3次,同时给予口服PPCC(易善复胶囊,赛诺菲-安万特(北京)制药有限公司),456 mg口服,每日3次,联合应用3个月;共服用3个月。对照组即单用PPCC组,17~49岁,平均(31.61 ± 8.52)岁,PICC,456 mg口服,每日3次,连用3个月。

2.4. 疗效判定

1) 显效:疗程结束临床症状完全消失或明显改善,肝内脂肪减少,TBIL、DBIL、ALT、AST明显降低至正常水平;2) 有效:疗程结束临床症状有所改善,TBIL、DBIL、ALT、AST 较治疗前下降50%;3) 无效:症状体征无改善,TBIL、DBIL、ALT、AST较治疗前降低不明显或病情加重 [4] 。

2.5. 生活指导

保持良好的精神状态和心理状态,消除恐惧心理,保持乐观情绪,提高治疗的依从性,配合治疗,坚持适度体育活动,纠正不良饮食习惯。

2.6. 统计学处理

所得数据用百分率及 表示,计量资料和计数资料差异比较分别t检验及方差分析,显著性水平为P < 0.05。

3. 结果

3.1. 中青年男性脂肪肝患者152例均进入结果分析

1) 疗效:两组治疗中青年男性NAFLD总有效率(显效及有效率)达94.74% (144/152)。观察组与对照组总有效率分别为97.37% (4/76)、92.11% (70/76) (P > 0.05)。2) 不良反应:出现轻度头昏、疲乏、恶心、腹部不适等不良反应,观察组与对照组分别为13.16% (10/76)、10.53% (8/76) (P > 0.05)。

3.2. 临床疗效

观察组显效36例(47.37%;36/76),有效38例(50%;38/76),无效4例(2.63%;2/76),对照组显效18例(23.68%;18/76),有效52例(68.42%;52/76),无效6例(2.63%;6/76),观察组总有效率高于对照组[97.37% (74/76);92.11% (70/76),(p < 0.01)]。在治疗过程中均未发现严重不良反应而停药或换药,复查肾功能、血电解质、血常规、尿常规、心电图均无明显变化,详见表3

3.3. 临床一般指标变化

两组患者的BMI及TBIL、DBIL、ALT、AST,和EN、C-P、FINS/FBG、HbA 1c 、TC、HDL-C、TG等结果具有明显改善,治疗组的FINS/FBG好于对照组(p < 0.01),详表1~3。

Table 1. General situation of the basic information of the two groups

表1. 两组基本信息情况()

注:与治疗前比较,*P < 0.05。

Table 2. Changes of liver function before and after treatment in two groups

表2. 两组治疗前后肝功能变化()

注:与治疗前比较,*P < 0.05。

Table 3. The changes of general clinical test index of two groups before and after treatment

表3. 两组一般指标治疗前后变化()

注:与治疗前比较,*P < 0.05。

4. 讨论

非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)已经成为临床上青壮年肝功能酶学异常和慢性肝病最常见的原因,NAFLD正成为人们健康的严重威胁之一 [5] - [7] 。近年来研究显示NAFLD与胰岛素抵抗、脂肪代谢紊乱、内毒素血症等密切相关,非酒精性单纯性脂肪肝(NAFLD)进展演变缓慢,具有肝细胞内脂肪堆积过多的病理特点,过多脂肪积蓄于肝脏,影响肝脏血液和养分供应及自身代谢,肝细胞会逐渐发生肿胀、炎症浸润、变性坏死,损伤肝功能,导致脂肪性肝炎 [8] [9] 。血中脂肪成分和酶类升高预示肝脏的代谢活力受到严重损伤,肝细胞线粒体结构有一定程度破坏,这种情况若长期发展,就会造成肝纤维化、肝硬化,极大增加患肝癌的危险 [10] 。有资料显示,约30%的酒精性脂肪肝可发展为肝硬化;约1.5%至8.0%的非酒精性脂肪肝可进展为肝硬化 [11] 。

多烯磷脂酰胆碱是治疗脂肪肝的基础用药,由大豆中提取的磷脂精制而成,其主要活性成分是1,2-二亚油酰磷脂酰胆碱(DLPC,人体不含),约占52%。DLPC可将人体内源性磷脂替换,结合并进入靶细胞膜成分中。这种取代的重要意义之一是增加靶细胞膜的流动性,同时还可以维持或促进不同器官及组织的许多活性细胞膜功能,包括可调节靶细胞膜结合酶系统的活性,能抑制细胞色素P4502E1(CYP2E1)的含量及活性,减少自由基,可增强过氧化氢酶活性、超氧化物歧化酶SOD活性和谷胱甘肽还原酶活性 [12] - [16] 。

脂肪肝属中医学积聚、胁痛等范畴,以肝经郁热、气滞血阻、痰瘀互结、瘀血内结为主要病机。调脂化瘀汤方中柴胡疏肝解郁,调和肝脏,行气止痛;茯苓利水渗湿,清利肝胆湿热;泽泻清热除湿,祛湿运脾;山楂消食健胃,活血化瘀;鸡内金健胃消食;丹参活血化瘀,清热凉血;姜黄破血行气,通经止痛;三七活血定痛;何首乌补肝肾、益精血;大黄荡涤胃肠湿热积滞,凉血止血,活血祛瘀,清泄湿热;虎杖行血消瘀,清解血分热毒,又可清利肝胆而除气分湿热;决明子疏肝理气,诸药合用,共奏行气滞、化痰瘀、清湿热之功。

中西医结合治疗脂肪肝一直是中外学者所关注的治疗方法 [17] - [21] ,GB与PICC合用,在功能上优势互补。PPCC体内分解后与内源性磷脂一样,进入肝细胞,并以完整的分子与肝细胞膜及细胞器膜相结合,直接影响膜结构使受损的肝功能和酶活力恢复正常,调节肝脏的能量平衡,促进肝组织再生,肝宝颗粒由柴胡、丹参、枸杞子、虎杖、黄芩瓜蒌、升麻、蒲公英等药物组成,具有疏肝健脾,祛湿化痰,理气和中,滋肾养肝、活血化淤、清热化痰等良好功效 [22] [23] 。GB中成分配伍合理,柴胡,减轻免疫功能破坏减轻肝细胞膜坏死和炎症反应,丹参,有活血化瘀,改善肝脏局灶受损组织血液循环作用,虎杖减轻肝脏局灶组织淤血作用,能够促进血小板生成,抵消脾功能亢进可能对血小板的破坏作用,改善血小板脆性度,瓜蒌使门脉的血流量减少,使门脉压力下降,使肝脏双循环系统达到稳态平衡,本临床观察显示GB联合PPCC对NAFLD治疗较单剂应用PPCC效果明显,前者总有效率(97.37%)高于对照组(92.11%),两者统计学处理差异显著(P > 0.05),观察组对恢复胰岛功能与降低血脂等方面,观察组明显优于对照组(p < 0.05),显示中药制剂GB具有良好调节胰岛细胞功能降低血脂作用,更能适合中青年脂肪肝血脂高、胰岛素抵抗、高体重指数的特点,GB安全性好,口服后很少对胃肠道产生刺激,对胃肠外器官,尤其是心血管系统无影响,无胃肠道副作用,费用适当,给药次数简单,患者的顺应性好,值得注意的是,对照组肠源性内毒素(Endotoxin, EN)的降低不如观察组,显示GB尚具有解毒功能,有研究表明,在老鼠NAFLD模型中小肠出现细菌过度生长,门静脉血清内毒素水平随之升高,肠道细菌过度生长是引起门静脉内毒素血症的重要原因之一,肠源性内毒素血症可能是脂肪肝的重要的发病机制之一,高血清内毒素加速脂肪肝的肝脏病理改变 [24] - [27] 肝宝颗粒的降低肠源性内毒素血症作用,有助于预防NAFLD的发生和发展。

文章引用

季洪赞,吴 琳,吴晓尉,李海兵,戎建明,施 慧,许莲娥,刘 炯,汪芳裕. 肝宝颗粒辅助易善复治疗非酒精性脂肪肝临床疗效观察
Clinical Observation of Traditional Chinese Medicine Preparation-Ganbao Particulate Adjuvant Treatment of Young and Middle-Aged Men with Non-Alcoholic Fatty Liver[J]. 临床医学进展, 2016, 06(01): 1-7. http://dx.doi.org/10.12677/ACM.2016.61001

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*第一作者。

#通讯作者。

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