酪酸梭菌活菌片联合多烯磷脂酰胆碱对酒精性肝病患者肠道菌群及炎症因子的影响
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摘要
目的探讨酪酸梭菌活菌片联合多烯磷脂酰胆碱对酒精性肝病(ALD)患者肠道菌群及炎症因子的影响。方法选取2015年1月至2018年1月进行治疗的ALD患者80例,随机分为观察组和对照组。两组患者均予以严格戒酒、高蛋白高热量低脂饮食、维生素及门冬氨酸钾镁等常规治疗。观察组患者在此基础上加用酪酸梭菌活菌片(0.7g/次,3次/d,口服)和多烯磷脂酰胆碱胶囊(456mg/次,3次/d,口服)联合治疗8周。对照组患者在常规治疗基础上单纯加用多烯磷脂酰胆碱片治疗,其剂量、用法及疗程与观察组相同。观察并比较治疗前后患者肝功能指标、肠道菌群数量及炎症因子的变化。结果治疗8周后,两组患者血清ALT、AST和TBiL水平均较治疗前显著下降(P<0.05),且观察组下降幅度较对照组更大(P<0.05)。两组患者肠道双歧杆菌和乳杆菌数量较治疗前明显上升,大肠埃希菌数量较治疗前明显下降(P<0.05),且观察组变化幅度较对照组更大(P<0.05)。两组患者血清IL-6和TNF-α水平较治疗前明显下降(P<0.05),且观察组下降幅度较对照组更大(P<0.05)。结论酪酸梭菌活菌片联合多烯磷脂酰胆碱能有效改善ALD患者肝功能指标,促进肝功能恢复,其作用机制可能与其能纠正肠道菌群失调,促进有益菌的繁殖,同时下调血清炎症因子水平,抑制肝内炎症反应密切相关。
Objective To discuss the effects of Clostridium Butyricum Tablets combined with polyene phosphatidyl choline on intestinal flora and inflammatory factors of patients with alcoholic liver disease(ALD).Methods 80 patients with ALD in our hospital from January 2015 to January 2018 were randomly divided into observation group or control group.Both groups were given routine medical treatment.The observation group was additionally given Clostridium Butyricum Tablets(0.7g tid orally)and Polyene Phosphatidyl Choline Capsules(456mg tidorally)for 8weeks,while the control group was given Polyene Phosphatidyl Choline Capsules alone with the same dose,method and course of treatment.The changes of liver function indexes,quantities of intestinal flora and inflammatory factors before and after treatment were observed and compared between groups.Results After 8weeks of treatment,the levels of serum ALT,AST and TBiL in both groups obviously declined(Ps<0.05),and the declining rates in observation group were much higher than those in control group(Ps<0.05).The quantities of Bifidobacteriaand Lactobacilli obviously increased,while that of Escherichia coli obviously declined(P<0.05),and the declining rate in observation group was much higher than that in control group(P<0.05).The levels of serum IL-6and TNF-αin both groups obviously declined(Ps<0.05),and the declining rates in observation group were much higher than those in control group(Ps<0.05)respectively.Conclusion Clostridium Butyricum Tablets combined with Polyene Phosphatidyl Choline can effectively improve the liver function indexes and speed the recovery of liver function,the mechanism of action of which may have close relation with its effects of not only adjusting the disorder of intestinal flora and speeding the reproduction of probiotics but also down-regulating the levels of serum inflammatory factors and inhibiting inflammatory reactions.
Objective To discuss the effects of Clostridium Butyricum Tablets combined with polyene phosphatidyl choline on intestinal flora and inflammatory factors of patients with alcoholic liver disease(ALD).Methods 80 patients with ALD in our hospital from January 2015 to January 2018 were randomly divided into observation group or control group.Both groups were given routine medical treatment.The observation group was additionally given Clostridium Butyricum Tablets(0.7g tid orally)and Polyene Phosphatidyl Choline Capsules(456mg tidorally)for 8weeks,while the control group was given Polyene Phosphatidyl Choline Capsules alone with the same dose,method and course of treatment.The changes of liver function indexes,quantities of intestinal flora and inflammatory factors before and after treatment were observed and compared between groups.Results After 8weeks of treatment,the levels of serum ALT,AST and TBiL in both groups obviously declined(Ps<0.05),and the declining rates in observation group were much higher than those in control group(Ps<0.05).The quantities of Bifidobacteriaand Lactobacilli obviously increased,while that of Escherichia coli obviously declined(P<0.05),and the declining rate in observation group was much higher than that in control group(P<0.05).The levels of serum IL-6and TNF-αin both groups obviously declined(Ps<0.05),and the declining rates in observation group were much higher than those in control group(Ps<0.05)respectively.Conclusion Clostridium Butyricum Tablets combined with Polyene Phosphatidyl Choline can effectively improve the liver function indexes and speed the recovery of liver function,the mechanism of action of which may have close relation with its effects of not only adjusting the disorder of intestinal flora and speeding the reproduction of probiotics but also down-regulating the levels of serum inflammatory factors and inhibiting inflammatory reactions.
引文
[1] Gao B,Bataller R.Alcoholic liver disease:Pathogenesis and new therapeutic targets[J]. Gastroenterology,2011,141(5):1572-1585.
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[3] Chen P,Torralba M,Tan J,et al.Supplementation of saturated long-chain fatty acids maintains intestinal eubiosis and reduces ethanol-induced liver injury in mice[J].Gastroenterology,2015,148(1):203-214
[4] HU Guoping,LIU Kai,ZHAO Liansan.Systematic evaluation of polyene phosphatidyl choline(essentiale)on alcoholic liver disease and fatty liver[J].Liver,2005,10(1):5-7.(in Chinese)胡国平,刘凯,赵连三.多烯磷脂酰胆碱(易善复)治疗酒精性肝病和脂肪肝的系统评价[J].肝脏,2005,10(1):5-7.
[5] LIANG Hui,LV Rui,FU Yong,et al.Research on protection effect and mechanism of probiotics on alcoholic liver damages of rats[J].Chin Pharmacol Bull,2016,32(7):991-997.(in Chinese)梁惠,吕锐,傅泳,等.益生菌对大鼠酒精性肝损伤的保护作用及机制研究[J].中国药理学通报,2016,32(7):991-997.
[6] Lv L,Hu X,Qian G,et al.Administration of Lactobacillus salivarius LI01or Pediococcus pentosaceus LI05improves acute liver injury induced by D-galactosamine-inrats[J].Appl Microbiol&Bitechnol,2014,98(12):5619-5632.
[7]中华医学会肝病学分会脂肪肝和酒精性肝病学组.酒精性肝病诊疗指南[J].临床肝胆病杂志,2010,26(3):229-232
[8] Matsushita N,Osaka T,Haruta I,et al.Effect of lipopolysaccharide on the progression of non-alcoholic fatty liver disease in high caloric diet-fed mice[J].Scand J Immunol,2016,83(2):109-118.
[9] Wang T,Liu Y,Kirpich I,et al.Lactobacillus rhamnosus GG reduces hepatic TNF production and inflammation in chronic alcoholinduced liver injury[J].J Nutrit Biochem,2013,24(9):1609-1615.
[10] Bull-Otterson L,Feng W,Kirpich I,et al.Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment[J].PloS One,2013,8(1):e53028
[11] Han SH,Suk KT,Kim DJ,et al.Effects of probiotics(culture Lactobacillus subtilis Streptococcus faecium)in the treatment of alcoholic hepatitis:Randomized-controlled multicenter study[J].Eur J Gastroenterol Hepatol,2015,27(11):1300-1306.
[12] Szabo G.Gut-liver axis in alcoholic liver disease[J].Gastroenterology,2015,148(1):30-36.
[13] Koga H,Tamiya Y,Mitsuyama K,et al.Probiotics promote rapid-turnover protein production by restoring gut flora in patients with alcoholic liver cirrhosis[J].Hepatol Int,2013,7(2):767-774.
[14] ZHANG Bo,LU Xiaolan,SONG Yahua,et al.Primary effect of intestinal environment on alcoholic fatty liver disease and curative effect of probiotics[J].Chin J Hepatol,2012,20(11):848-852.(in Chinese)张波,鲁晓岚,宋亚华,等.肠道内环境在酒精性脂肪肝发病中的初始作用及益生菌的治疗效果[J].中华肝脏病杂志,2012,20(11):848-852.
[15]谢凯元,吕小萍.口服酪酸梭菌活菌片对肝硬化患者肠道通透性的影响[J].中国药物与临床,2011,11(11):1314-1315.
[2] Kirpich IA,Solovieva NV,Leikhter SN,et al.Probiotics restore bowel flora and improve liver enzymes in human alcohol-induced liver injury:A pilot study[J].Alcohol,2008,42(8):675-682.
[3] Chen P,Torralba M,Tan J,et al.Supplementation of saturated long-chain fatty acids maintains intestinal eubiosis and reduces ethanol-induced liver injury in mice[J].Gastroenterology,2015,148(1):203-214
[4] HU Guoping,LIU Kai,ZHAO Liansan.Systematic evaluation of polyene phosphatidyl choline(essentiale)on alcoholic liver disease and fatty liver[J].Liver,2005,10(1):5-7.(in Chinese)胡国平,刘凯,赵连三.多烯磷脂酰胆碱(易善复)治疗酒精性肝病和脂肪肝的系统评价[J].肝脏,2005,10(1):5-7.
[5] LIANG Hui,LV Rui,FU Yong,et al.Research on protection effect and mechanism of probiotics on alcoholic liver damages of rats[J].Chin Pharmacol Bull,2016,32(7):991-997.(in Chinese)梁惠,吕锐,傅泳,等.益生菌对大鼠酒精性肝损伤的保护作用及机制研究[J].中国药理学通报,2016,32(7):991-997.
[6] Lv L,Hu X,Qian G,et al.Administration of Lactobacillus salivarius LI01or Pediococcus pentosaceus LI05improves acute liver injury induced by D-galactosamine-inrats[J].Appl Microbiol&Bitechnol,2014,98(12):5619-5632.
[7]中华医学会肝病学分会脂肪肝和酒精性肝病学组.酒精性肝病诊疗指南[J].临床肝胆病杂志,2010,26(3):229-232
[8] Matsushita N,Osaka T,Haruta I,et al.Effect of lipopolysaccharide on the progression of non-alcoholic fatty liver disease in high caloric diet-fed mice[J].Scand J Immunol,2016,83(2):109-118.
[9] Wang T,Liu Y,Kirpich I,et al.Lactobacillus rhamnosus GG reduces hepatic TNF production and inflammation in chronic alcoholinduced liver injury[J].J Nutrit Biochem,2013,24(9):1609-1615.
[10] Bull-Otterson L,Feng W,Kirpich I,et al.Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment[J].PloS One,2013,8(1):e53028
[11] Han SH,Suk KT,Kim DJ,et al.Effects of probiotics(culture Lactobacillus subtilis Streptococcus faecium)in the treatment of alcoholic hepatitis:Randomized-controlled multicenter study[J].Eur J Gastroenterol Hepatol,2015,27(11):1300-1306.
[12] Szabo G.Gut-liver axis in alcoholic liver disease[J].Gastroenterology,2015,148(1):30-36.
[13] Koga H,Tamiya Y,Mitsuyama K,et al.Probiotics promote rapid-turnover protein production by restoring gut flora in patients with alcoholic liver cirrhosis[J].Hepatol Int,2013,7(2):767-774.
[14] ZHANG Bo,LU Xiaolan,SONG Yahua,et al.Primary effect of intestinal environment on alcoholic fatty liver disease and curative effect of probiotics[J].Chin J Hepatol,2012,20(11):848-852.(in Chinese)张波,鲁晓岚,宋亚华,等.肠道内环境在酒精性脂肪肝发病中的初始作用及益生菌的治疗效果[J].中华肝脏病杂志,2012,20(11):848-852.
[15]谢凯元,吕小萍.口服酪酸梭菌活菌片对肝硬化患者肠道通透性的影响[J].中国药物与临床,2011,11(11):1314-1315.