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医药导报
医药导报, 2019, 38(5): 603-606
doi: 10.3870/j.issn.1004-0781.2019.05.016
益生菌制剂辅助治疗中重度脂肪肝患者肠功能紊乱的临床疗效*
Clinical Effect of Probiotics on Intestinal Dysfunction in Patients with Non-alcoholic Fatty Liver Disease
任习芳1,, 张丽静2,
1.武汉大学基础医学院生物化学系,武汉 430071
2.三峡大学人民医院消化内科,宜昌 443000
REN Xifang1,, ZHANG Lijing2,
1.Department of Biochemistry, Basic Medical College, Wuhan University, Wuhan 430071, China
2.Department of Gastroenterology, the People’s Hospital of China Three Geoges University, Yichang 443000,China;
通信作者 张丽静(1984-),女,河北宁晋人,主治医师,博士,研究方向:非酒精性脂肪肝的危险因素及临床诊疗工作。电话:0717-6287502,E-mail:zhanglijingtougao@163.com。

作者简介 任习芳(1973-),女,土家族,湖北宜昌人,副主任医师,硕士,研究方向:非酒精性脂肪肝的危险因素及临床诊治。ORCID:0000-0002-7990-3274。电话:0717-6287502,E-mail:rxfcc@163.com。
基金资助: 2013年宜昌市科学研究与开发项目医疗卫生课题(A13301-29)
中图分类号: R975;R575.5     文献标识码: B     文章编号: 1004-0781(2019)05-0603-04
摘要:

目的 观察益生菌制剂辅助治疗非酒精性脂肪性肝病(NAFLD)患者肠功能紊乱的疗效,探讨NAFLD与肠道内环境之间的关系和相互作用。方法 中重度NAFLD肠功能紊乱患者122例,随机分为A组34例,B组48例,C组40例,在基础治疗(控制饮食+运动)的同时,A组给予多烯磷脂酰胆碱胶囊456 mg;B组给予多烯磷脂酰胆碱胶囊456 mg +胰酶肠溶胶囊0.3 g;C组给予多烯磷脂酰胆碱胶囊456 mg +胰酶肠溶胶囊0.3 g +双歧杆菌三联活菌胶囊420 mg,均为每天3次口服,疗程均为1个月。监测血生化指标及肠功能紊乱症状。结果 B组、C组治疗后肠功能紊乱症状明显好转;B组和C组腹泻有效率分别为50.0%,65.0%,里急后重有效率分别为20.8%,30.0%,肛门排气有效率分别为22.9%,37.5%(均P<0.05)。结论 多烯磷脂酰胆碱胶囊+胰酶肠溶胶囊+双歧杆菌三联活菌胶囊联合治疗对NAFLD患者肠功能紊乱具有良好的疗效;肠道内环境与肝脏关系密切,肠菌群失调在NAFLD的发生发展中起着重要的作用。
关键词: 益生菌制剂 ; 脂肪肝 ; 非酒精性 ; 肠功能紊乱

Abstract:

Objective To observe the therapeutic efficacy of probiotics in the treatment of intestinal dysfunction in patients with non-alcoholic fatty liver disease (NAFLD), and to explore the relationship and interaction between NAFLD and intestinal environment. Methods A total of 122 patients with modest to severe NAFLD complicated by intestinal dysfunction were randomly divided into group A (n=34), group B (n=48), group C (n=40). All patients received a basic treatment of calorie control diet and exercise. Moreover, group A was given polyene phosphatidylcholine (PP) capsule 456 mg; group B was given PP capsule 456 mg + pancreatin enteric-coated (PC) capsule 0.3 g; and group C was given PP capsules 456 mg + PC capsules 0.3 g + bifidobacterium, lactobacillus and enterococcus (BLE) capsule 420 mg. All medications were taken orally 3 times a day, and the course of treatment was 1 month. The routine blood test and symptoms of intestinal dysfunction were evaluated and monitored. Results Comparing to group A, the symptoms of intestinal dysfunction were significantly improved in group B and group C. The effective rate of diarrhea in group B and group C was 50.0% and 65.0%, respectively (P<0.05). The efficiency of tenesmus in group B and group C was 20.8% and 30.0% (P<0.05); and the anal exhaust efficiency in group B and group C was 22.9% and 37.5% (P<0.05). Conclusion The PP capsule + PC capsules + BLE capsule combination therapy has good curative effect on intestinal dysfunction in patients with NAFLD. The intestinal environment is closely related to liver, thus intestinal flora imbalance in NAFLD may play an important role in the disease development.
Key words: Probiotic preparation ; Non-alcoholic fatty liver disease ; Intestinal dysfunction

非酒精性脂肪性肝病(non-alcoholic fatty liver disease ,NAFLD)是指除外酒精和其他明确的损肝因素所致的肝细胞内脂肪过度沉积为主要特征的临床病理综合征,与胰岛素抵抗和遗传易感性密切相关的获得性代谢应激性肝损伤[1]。不同于其他常见慢性肝脏疾病,NAFLD被视为全身性系统性慢性炎症状态[2]。其除与2型糖尿病、慢性肾脏疾病、心脑血管事件的发生密切关联外,尚与结直肠肿瘤、甲状腺功能减退、骨质疏松等众多肝外并发症有关[3,4]。肠道与肝脏在功能上也存在广泛的联系,肠道黏膜屏障功能受损可促进NAFLD的发生和发展[5]。研究肠道对于NAFLD影响,可能找到从肠道入手治疗NAFLD的途径和策略。目前,使用益生菌制剂治疗NAFLD较少见。2015年3月—2017年3月,笔者使用益生菌制剂对 NAFLD患者肠功能紊乱进行干预,观察益生菌对NAFLD肠道功能的影响,探讨脂肪肝与肠道内环境之间密切关系及相互作用。

1 资料与方法
1.1 临床资料

选取三峡大学人民医院体检中心及门诊确诊的NAFLD 患者122例,其中中度NAFLD 78例,重度NAFLD 44例,均合并超重或肥胖。NAFLD入选患者具备下列第1~5项:①无饮酒史或饮酒折合乙醇量男性每周<140 g,女性每周<70 g;②除外病毒性肝炎、药物性肝病、全胃肠外营养、肝豆状核变性等可导致脂肪肝的特定疾病;③可有体质量超重和(或)内脏性肥胖、空腹血糖增高、血脂紊乱、高血压等代谢综合征(metabolic syndrome,MS)相关组分;④血清转氨酶和γ-谷氨酞转移酶(GGT)水平可有轻至中度增高(小于5倍正常值上限);⑤肝脏影像学表现符合弥漫性脂肪肝的影像学诊断标准。 所有患者均为初次来我院就诊,治疗前均行结肠镜检查,排除器质性病变,如结直肠肿瘤、息肉、炎症性肠病、肠结核、缺血性肠病等,大便培养排除肠道感染性疾病,查大便常规+潜血阴性。122例 NAFLD 患者在超重或肥胖的基础上还合并MS其他组分(如糖代谢异常、血压升高、血脂异常),其中仅合并超重或肥胖28例;合并2个 MS组分者41例;合并3个 MS 组分者38 例;合并4个MS 组分者15例。122例NAFLD患者分层随机分为A组34例,B组48例,C组40例。本次研究相关检查均得到所有研究对象的知情同意。

3组患者临床资料进行两组间比较,如性别、年龄、身高、收缩压(SBP)、体质量指数(BMI)、腰围等均差异无统计学意义(均P>0.05),见表1。

表1 3组患者基线指标比较
Tab.1 Comparison of baseline data among three groups of patients x¯±s
组别 例数 性别 年龄/
岁		 收缩压/
mmHg		 体质量指数/
[kg·(m2)-1]		 腰围/
cm
男 女
A组 34 25 9 39.46±8.02 124.22±9.60 27.67±2.01 91.64±4.56
B组 48 40 8 40.79±11.62 123.28±10.96 28.54±2.45 92.87±7.01
C组 40 36 4 40.06±7.12 123.16±9.52 27.19±1.25 91.82±3.23

表1 3组患者基线指标比较

Tab.1 Comparison of baseline data among three groups of patients x¯±s

1.2 治疗方法

3组均行基础治疗(控制饮食+运动),A组(对照组)同时口服多烯磷脂酰胆碱胶囊;B组口服多烯磷脂酰胆碱胶囊+胰酶肠溶胶囊;C组口服多烯磷脂酰胆碱胶囊+胰酶肠溶胶囊+双歧杆菌三联活菌胶囊。用法:多烯磷脂酰胆碱胶囊(商品名为易善复,赛诺菲北京制药有限公司,批准文号:国药准字H20059010 )456 mg(2粒),每天3次,随餐服用;胰酶肠溶胶囊(商品名为得每通,AbbottLaboratories GmbH,批准文号:国药准字H20160180),0.3 g(2粒),每天3次,随餐服用;双歧杆菌三联活菌胶囊(商品名为培菲康,上海信谊药厂有限公司 ,批准文号:国药准字S10970105) 420 mg(2粒),每天3次,餐后0.5 h服用。3组疗程均为1个月。

1.3 观察指标

采用日立 7600 全自动生化分析仪及其配套试剂检测血生化指标。全部研究对象行生化指标、代谢指标检测,采血前应禁食8~10 h,次晨于我院体检中心采集血清检测:①肝脏生化指标,天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、γ-GGT。②代谢指标,总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、尿酸(UA)、空腹血糖(FBG)。

1.4 统计学方法

采用SPSS 17.0版软件包对所收集的数据进行统计分析和比较。计数资料采用卡方检验,计量资料用均数±标准差( x ¯ ±s)表示,两组比较用 LSD-t检验或秩和检验(非正态分布),以 P<0.05 为差异有统计学意义。

2 结果
2.1 3组治疗前后肝功能、血脂水平、血尿酸、空腹血糖的变化情况

见表2。A、B、C组治疗前后血尿酸、TG、总胆固醇、转氨酶、空腹血糖检测指标差异有统计学意义(P<0.05)。但B组、C组与A组治疗后各项指标比较差异无统计学意义(P>0.05);C组与B组各项指标治疗后比较差异无统计学意义(P>0.05)。

表2 3组治疗前后肝功能、血脂水平、血尿酸、空腹血糖指标比较
Tab.2 Comparison of the indexes of liver function, blood lipid, blood uric acid and fasting blood glucose among three groups of patients before and after the treatment x¯±s
组别与时间 例数 ALT AST TC TG
( U·L-1) (mmol·L-1)
A组 34
治疗前 62.65±38.30 53.17±30.47 5.65±1.07 2.85±1.23
治疗后 41.43±36.65 39.76±25.44 4.78±1.45 1.79±0.36
B组 48
治疗前 63.56±40.31 53.91±26.45 5.67±1.35 2.96±0.68
治疗后 62.23±42.31*1 40.36±24.28*1 4.62±1.18*1 1.45±0.66*1
C组 40
治疗前 62.36±30.10 50.25±27.17 5.39±1.52 2.91±1.23
治疗后 41.83±33.26*1*2 39.76±22.41*1*2 4.28±1.45*1*2 1.86±0.45*1*2
组别与时间 HDL LDL UA/
(μmol·L-1)		 FBG/
(mmol·L-1)
(mmol·L-1)
A组
治疗前 1.35±0.66 2.96±0.54 380.42±80.32 5.63±0.50
治疗后 1.12±0.47 2.32±0.78 311.91±68.58 4.69±0.54
B组
治疗前 1.28±0.18 3.25±0.62 379.58±70.51 5.56±0.76
治疗后 1.16±0.56*1 2.56±0.45*1 316.52±69.32*1 4.56±0.38*1
C组
治疗前 1.55±0.26 3.16±0.55 385.43±79.26 5.03±0.50
治疗后 1.02±0.42*1*2 2.22±0.18*1*2 291.91±53.50 *1*2 3.90±0.44*1*2

与A组治疗后比较,*1P<0.05;与B组治疗后比较,*2P<0.05

Compared with group A after treatment,*1P<0.05;Compared with group B after treatment,*2P<0.05

表2 3组治疗前后肝功能、血脂水平、血尿酸、空腹血糖指标比较

Tab.2 Comparison of the indexes of liver function, blood lipid, blood uric acid and fasting blood glucose among three groups of patients before and after the treatment x¯±s

2.2 3组治疗前后肠功能症状的改善情况比较结果

见表3。A、B、C组腹泻有效率分别为5.9%,50.0%,65.0%;里急后重有效率分别为2.9%,20.8%,30.0%;肛门排气有效率分别为2.9%,22.9%,37.5%。 A、B、C组治疗后腹痛、腹泻、腹胀、肠鸣、大便黏液、里急后重及肛门排气等有效率比较有统计学意义(P<0.05)。C组腹泻、里急后重、肛门排气等与B组治疗后有效率差异有统计学意义(P<0.05)。

表3 3组治疗前后肠功能紊乱症状的改善情况比较
Tab.3 Comparison of the improvement of intestinal dsyfuction among three groups of patients before and after the treatment %
组别与时间 例数 腹痛 腹泻 腹胀 肠鸣 大便黏液 里急后重 肛门排气
例 % 例 % 例 % 例 % 例 % 例 % 例 %
A组 34
治疗前 13 38.2 32 94.1 31 91.2 30 88.2 20 58.8 14 41.2 16 47.1
治疗后 8 23.5 30 88.2 30 88.2 29 85.3 29 85.3 13 38.2 15 44.1
B组 48
治疗前 18 37.5 43 89.6 40 83.3 44 91.7 27 56.2 19 39.6 23 47.9
治疗后 11 22.9*1 19 39.6*1 12 25.0*1 19 39.6*1 11 22.9*1 9 18.8*1 12 25.0*1
C组 40
治疗前 17 42.5 36 90.0 35 87.5 38 95.0 22 55.0 16 40.0 22 55.0
治疗后 7 17.5*1 10 25.0*1*2 12 30.0*1 13 32.5*1 6 15.0*1 4 10.0*1*2 7 17.5*1*2

与A组治疗后比较,*1P<0.05;与B组治疗后比较,*2P<0.05

Compared with group A after treatment,*1P<0.05;Compared with group B after treatment,*2P<0.05

表3 3组治疗前后肠功能紊乱症状的改善情况比较

Tab.3 Comparison of the improvement of intestinal dsyfuction among three groups of patients before and after the treatment %

3 讨论

人体肠道是一个巨大的细菌库,包括有益菌及有害菌,各种细菌相互制约,相互依存,维持人体肠道菌群的平衡状态。随着“肠-肝”轴 [6]的提出,再次证明 NAFLD 存在肠黏膜屏障的损伤及肠道菌群失调。肠道微生态失调可影响宿主营养吸收及能量储存,增加肠黏膜的通透性,破坏肠道免疫功能,导致大量肠道有害物质经门静脉入肝[7]。小肠细菌过度性生长的现象在NAFLD患者中很常见[8],通过引入益生菌改善肠道内微生物菌群环境,可抑制致病性细菌的过度生长,从而在NAFLD的治疗中发挥积极影响。

在NAFLD治疗中,多烯磷脂酰胆碱胶囊主要修复受损的肝细胞膜,减少脂质过氧化损伤,降低血中的三酰甘油及胆固醇含量[9,10],治疗1个月后,3组肝功能、尿酸、血糖、血脂指标均明显改善。胰酶肠溶胶囊中含有活性酶含量较高的脂肪酶,能促进脂肪的消化及吸收,有效减少肠道内未消化食物的蓄积,降低肠道菌群产物(尤其是气体),进而对排便和排气情况有显著的改善作用[11]。B组、C组与A组治疗后腹痛、腹泻、腹胀、腹鸣、大便黏液、肛门排气等均得到明显缓解。在腹泻、里急后重、肛门排气方面C组有效率明显高于B组(P<0.05)。双歧杆菌三联活菌胶囊属于益生菌制剂,是由粪肠球菌、嗜酸乳杆菌、双歧杆菌联合组成的活菌制剂,主要在小肠内吸收,抑制小肠细菌的过度生长,纠正肠道菌群失调,促进有益菌的生长,抑制尿素酶细菌、腐败菌等的生长,进一步缓解肠道功能紊乱,特别是在腹泻、里急后重、肛门排气等方面。也能够酸化肠道,从而降低血清内毒素,减轻肝脏炎症反应,改善肝功能,并使患者临床症状得到改善。微生态制剂能调整肝病患者的肠道菌群失调,减少肠源性内毒素的产生,减少对肝脏的损伤,预防或者改善腹泻[12]。

结合国内外相关研究[13,14,15],NAFLD发生肠功能紊乱原因为:①肠道菌群失调;②肠道屏障损伤;③消化吸收不良;④植物神经功能紊乱,肠道蠕动加快,出现腹痛、腹胀、腹鸣,大便性状改变。其中,肠道菌群失调在 NAFLD 的发生发展中起到不可忽视的作用。通过多烯磷脂酰胆碱胶囊、双歧杆菌三联活菌胶囊和胰酶肠溶胶囊联合治疗,不仅患者血生化指标明显好转,肠道功能紊乱也得到有效控制。肠道益生菌调节肠道功能的作用机制可能为:①益生菌在肠道内仍保持活性,通过利用其代谢及生长作用,保持肠道内菌群的正常,抑制肠内腐败物质的产生;②益生菌保持肠道菌群最佳的稳定性及优势组合;③免疫调理作用,通过维持肠道功能的完整性,减轻脂肪肝细胞的免疫应激及肝损伤。因此对NAFLD患者给予益生菌调节肠道菌群治疗,可恢复肠道微生态平衡,减轻肠源性内毒素血症,减少对肝细胞形成“二次打击”,对延缓乃至阻止 NAFLD进展为肝纤维化、肝硬化可能有重要作用。

The authors have declared that no competing interests exist.
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[4] ARMETRONG M J,ADAMS LA,CANBAY A,et al.Extrahepatic complications of no nalcoholic fatty liver disease[J].Hepatology,2014,59(10):1174-1197.
Nonalcoholic fatty liver disease (NAFLD) is an important cause of liver disease that is often associated with the metabolic syndrome. There is a growing awareness that extrahepatic complications occur in individuals with NAFLD, especially an increased risk of cardiovascular disease. Development of diabetes mellitus, chronic kidney disease, colorectal cancer, and endocrinopathies has been linked to NAFLD. This article reviews the extrahepatic complications affecting individuals with NAFLD and the pathogenesis underlying their development.
DOI:10.1002/hep.26717      PMID:24002776      URL    
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[5] 刘涛,徐秋玲,赵岩.非酒精性脂肪肝大鼠肠道黏膜屏障功能的实验研究[J].医学研究生学报,2015,11(28):1124-1127.
目的：肠道黏膜屏障功能紊乱与非酒精性脂肪肝（ non-alcohol fatty liver disease ，NAFLD）的发生关系密切，文中旨在通过动物模型的方法探讨NAFLD大鼠肠道黏膜屏障功能。方法 SD大鼠16只按随机数字表法分为正常组和NAFLD组，每组8只。正常组由普通饲料喂养，每100克普通饲料提供326 kCal热量。 NAFLD组大鼠由高脂饲料喂养，每100克高脂饲料提供453 kCal热量建立NAFLD模型。采用HE染色检测肝病理， Elisa法和鲎试剂法分别检测肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-1（Interleukin-1，IL-1）、内毒素，实时定量PCR法检测小肠闭锁小带蛋白ZO-1和连接蛋白Occluding的表达。结果 NAFLD组大鼠肝呈现典型的脂质沉积，血浆内毒素和血清TNF-α、IL-1较正常组显著增高，小肠ZO-1和Occluding表达较正常组显著降低（P＜0．05）。结论 NAFLD大鼠存在肠道黏膜屏障功能下降。
DOI:10.16571/j.cnki.1008-8199.2015.11.002      URL    
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[6] 孙之梅,袁瑜,何祥.肠道微生态变化与非酒精性脂肪性肝病研究[J].实用肝脏病杂志,2013,16(3):275-278.
由定植于肠道的大量固有菌群、肠道上皮细胞及肠道局部粘膜免疫系统组成了肠道微生态系统.“肝-肠轴”概念的提出为从肠道微生态角度寻找非酒精性脂肪性肝病(NAFLD)的诊疗措施提供了依据.肠道微生态失衡所致的肠道菌群过度生长、肠黏膜通透性改变、免疫功能紊乱、肠源性内毒素血症、效应细胞激活及炎症因子生成等在NAFLD发生发展中发挥了不容忽视的作用.深入研究肠道菌群与NAFLD之间的关系将为NAFLD的预防和治疗提供新靶点.
DOI:10.3969/j.issn.1672-5069.2013.03.030      URL    
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[7] 倪曼曼,曾欣,陈岳祥.肠道微生态与非酒精性脂肪性肝病关系的研究进展[J].国际消化病杂志,2016,35(2):40-42.
非酒精性脂肪性肝病（NAFLD）是一种与胰岛素抵抗和遗传易感性密切相关，以肝实质细胞脂肪变性和脂质沉积为特征的临床病理综合征。近年来研究发现，肠道微生态失衡通过干扰宿主物质代谢、促进胰岛素抵抗、破坏肠道免疫功能，在 NAFLD 的发生发展中起重要作用。采用微生态制剂调节和重建肠道微生态也成为 NAFLD 防治的热点。此文就肠道微生态与 NAFLD 关系的研究进展作一综述。
DOI:10.3969/j.issn.1673-534X.2016.01.009      URL    
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[8] 牛海艳,李海,丁玉平.非酒精性脂肪肝的治疗研究进展[J].临床肝胆病杂志,2018,34(2):436-437.
随着人们生活水平的不断提高,脂肪肝的发病率也逐年提高。人们日益意识到脂肪肝给生命健康带来的重大影响。近年来医学界为有效的治疗非酒精性脂肪肝不懈努力,取得了一定的疗效与成果,目前西医多从生活方式的改变来纠正脂肪肝,辅助对症处理,药物治疗。中医多从整体观念出发,以人为本,辨证论治。文章主要就中、西医常见治疗方法和药物做一综述。
DOI:10.13699/j.cnki.1001-6821.2018.20.017      URL    
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[9] WU C X,CHEN Y H,ZHOU X L,et al.Effect of polyene phosphatidyl choline combined with lipd-lowering drugs in treatment of nonalcoholic fatty liver disease[J]. Chin J Liver Dis(Electr Version),2012,4(2):17-20.
Objective To investigate the effect and safety of polyene phosphatidyl choline combined with lipid-lowering drugs in treatment of nonalcoholic fatty liver disease.Methods Total of 103 patients with nonalcoholic fatty liver disease were selected and divided randomly into two groups.In therapeutic group,the patients received polyene phosphatidyl choline combined with simvastatin(n = 55) for 12 weeks.While in control group,the patients received simvastatin,Vitamin C and inosine(n = 48) for 12 weeks.The levels of serum transaminase,clinical symptom,blood grease and image changes of B ultrasonic before and after treatment were compared,respectively.Results The levels of serum transaminase,clinical symptom,blood grease and image changes of B ultrasonic improved obviously after treatment,with the efficiency as 87.3% and 52.1% in therapeutic group and control group,respectively.There were significant difference between the two groups on the improvement of clinical symptome,liver function and blood fat(P 0.05).Conclusions Treatment of nonalcoholic fatty liver disease with simvastatin combined with polyene phosphatidyl choline is safe and effective.
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[10] 刘义荣,梁珊,聂巍,等.多烯磷脂酰胆碱对非酒精性脂肪肝患者IL-6、TNF-α的影响[J].山东医药,2014,54(29):47-48.
目的：观察多烯磷脂酰胆碱（ PPC）对非酒精性脂肪肝（ NAFLD）患者血清IL-6、TNF-α水平的影响。方法将60例NAFLD患者随机分为A、B组各30例。 A组口服PPC治疗，B组口服水飞蓟宾甲葡胺治疗，疗程均为3个月。检测两组治疗前、治疗3个月及停药后2周的血脂及肝功能，血清IL-6、TNF-α、 空腹胰岛素（Fins）及胰岛素抵抗指数（ HOMA-IR）等指标；并与10例查体健康者（对照组）进行比较。结果与B组比较，A组治疗3个月及停药后2周的血脂、肝功能、IL-6、TNF-α均 明显降低（P均＜0．05），IL-6、TNF-α水平与对照组接近；A组治疗3个月及停药2周后Fins、HOMA-IR均较B组明显好转（P均 ＜0．05）。结论 PPC可明显改善NAFLD患者的肝功能，降低其血清TNF-α、IL-6水平，改善预后。
DOI:10.3969/j.issn.1002-266X.2014.29.019      URL    
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[11] SABEL,NIKOVA E A.Clinical aspects of intestinal dysbacteriosis[J].Eksp Klin Gastroenterol,2011,(3):111-116.
The article presents data of domestic and foreign literature on intestinal dysbacteriosis. It is evident that intestinal dysbiosis always secondary and its correction should take into account the reasons that caused the violation of the microbial composition of the intestinal flora and the clinical manifestations of this syndrome. The characteristic of the normal intestinal microflora and its significance for the human body. It was emphasized that the resident microflora influences the development of the immune response of the intestinal mucosa, epithelial differentiation and proliferation, motility, is actively involved in the digestion and absorption, and synthesis of vitamins and bioactive substances. It was described factors leading to violation of the microbial composition of intestine, as well as methods of diagnosis and treatment of dysbiosis. Therapeutic measures for dysbiosis conducted according to the nature and severity of underlying disease and were in compliance with dietary recommendations and the use of drugs, normalizing the intestinal microflora. In order to remove from the intestinal lumen conditionally pathogenic microorganisms and toxins using different chelators. One of the members of this group of drugs is Laktofiltrum. Laktofiltrum drug effective in treating patients with bowel diseases, accompanied by dysbiosis, as a monotherapy and in combination with other drugs.
PMID:21698814     
[本文引用:1]
[12] 中国预防医学会微生态学分会.中国消化道微生态调节剂临床应用共识[J].中国微生态杂志,2016,28(6):621-631.
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[13] QIN Q F,LI H F.The progress of researches on chronic liver disease and intestinal flora[J].Chin J Microecol,2012,24(5):476-477.
The liver was closely related to gut microflora.Chronic liver disease patients had alteration of intestinal flora,which was associated with increasing endotoxin blood,hepatic encephalopathy,and the occurrence of superinfection.Imbalanced intestinal flora promoted the occurrence and progression of complications of chronic liver disease,increased mortality,and was proportional to the degree of liver dysfunction.Probiotics could restore intestinal flora balance,maintain the integrity of the intestinal barrier,inhibit the amount of G-,reduce the production of intestinal ammonia,and aid in the treatment of chronic liver disease.
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[14] 曹力,韩四海,高红丽,等.乳酸杆菌调节肠道黏膜屏障功能的研究进展[J].中国免疫学杂志,2016,32(3):419-423.
正益生菌是指摄入足够的数量,对宿主健康能够产生有益作用的活的微生物。益生菌可通过影响肠道微生物区系发挥对宿主的健康起促进作用。许多研究表明,益生菌对人的健康作用包括:缓解乳糖不耐受症、免疫调节、降低粪便中的酶活及突变的发生、降低胆固醇及肠道疾病的发生。乳酸杆菌作为益生菌通常用于治疗和预防肠道
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[15] YANG L H,CAI J,LIU G D,et al.Relationship of disturbance of intestinal flora,intestinal permeability and serum endotoxin in patients with NASH[J].Chin J Microecol ,2012,24(9):801-804.
Objective To investigate the relationship of disturbance of intestinal flora,intestinal permeability and plasma endotoxin in patients with nonalcoholic steatohepatitis(NASH).Methods Representative bacteria in intestinal flora were cultivated and counted routinely.The subjects were divided into 2 groups: healthy control group(group A,n=30) and NASH group(group B,n=30).Their intestinal flora,serum endotoxin,diamine oxidase,D-lactate and TNF alpha levels were detected respectively.Results Compared with group A,bacillus bifidus,bacillus lactis and bacteroides decreased(P0.01 or P0.05),enterobacteria and enterococcus increased(P0.01 or P0.05),and serum endotoxin,diamine oxidase,D-lactate and TNF alpha levels increased remarkably(P0.01) in group B.The enterobacteria correlated with serum endotoxin,dia-mine oxidase and D-lactate(r=0.644,P0.001;r=0.415,P=0.023;r=0.383,P=0.037);serum endotoxin correlated with diamine oxidase,D-lactate and TNF alpha(r=0.485,P=0.007;r=0.477,P=0.008;r=0.490,P=0.006);TNF alpha correlated with diamine oxidase and D-lactate(r=0.426,P=0.019;r=0.440,P=0.015).Conclusion Alteration of intestinal flora,increasing of intestinal permeability and intestinal endotoxemia existed in patients with NASH and the overgrowth of enterobacteria correlated with intestinal permeability and serum endotoxin positively.
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关键词（key words）
益生菌制剂
脂肪肝
非酒精性
肠功能紊乱
Probiotic preparation
Non-alcoholic fatty liver...
Intestinal dysfunction
作者
任习芳
张丽静
REN Xifang
ZHANG Lijing