肠道益生菌辅助治疗非酒精性脂肪性肝病的临床研究

Efficacy of probiotics on the treatment of non-alcoholic fatty liver disease

目的 探讨益生菌辅助治疗非酒精性脂肪性肝病（NAFLD）的疗效.方法 2010年12月—2015年12月北京医院确诊的200例NAFLD患者采用随机数字表法分为对照组和联合治疗A组、B组和C组,每组各50例.药物治疗方案：对照组为常规药物治疗组,给予口服多烯磷脂酰胆碱胶囊;联合治疗A组、B组和C组在常规药物治疗基础上分别联用＂双歧三联活菌＂＂枯草杆菌肠球菌二联活菌＂和＂双歧三联活菌＋枯草杆菌肠球菌二联活菌＂;疗程为1个月.所有患者均于治疗前、治疗后第30天检测血脂、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、空腹血糖（FPG）、血清高分子量脂联素（HMW-APN）及肿瘤坏死因子α（TNFα）水平;并采集粪便标本,进行常规检测和细菌培养;同时行肝脏B超,评估脂肪肝情况.结果 （1）在血糖、血脂方面,各组治疗1个月后均较治疗前有所改善,除高密度脂蛋白胆固醇（HDL-C）外差异均有统计学意义.（2）在肝功能方面,治疗后各组的血清ALT、AST均低于治疗前（P值均〈0.01）;治疗后联合治疗C组的血清ALT、AST水平低于对照组[（33.7±7.6）U/L比（45.0±8.5）U/L;（22.0±1.6）U/L比（29.4±3.7）U/L;P〈0.05].（3）治疗后,各组的血清TNFα水平均下降;联合治疗C组的TNFα水平明显低于对照组[（0.51±0.27）μg/L比（0.82±0.28）μg/L,P〈0.05].（4）治疗后,各组血清HMW-APN均升高;联合治疗C组的HMW-APN水平高于对照组[（9.28±3.72）μg/L比（7.87±3.96）μg/L,P〈0.05].（5）治疗后,对照组和各联合治疗组的肝脏B超检查结果显示脂肪肝较治疗前均有改善,但各联合治疗组与对照组的差异均无统计学意义.（6）与治疗前相比,联合治疗各组治疗后的粪便菌群积分均有所降低（P值均〈0.01）,而对照组治疗前后差异无统计学意义.结论 益生菌可通过改善NAFLD患者肠道微生态失衡,辅助降低血TNFα,提升血脂联素水平,从而改善血糖、血脂代谢,并改善NAFLD的肝脏损伤.

Objective To study the clinical effect of probiotics in the treatment of non-alcoholic fatty liver disease （NAFLD）. Methods A total of 200 patients with NAFLD were randomly divided into 4 groups： control group （routine treatment group） and combined treatment group A, B and C. Each group had equal patients. The control group received orally polyene phosphatidylcholine capsules; whereas combined group A, B and C were given orally the live＂combined Bifidobacterium Lactobacillus and Enterococcus powder＂,＂two live combined Bacillus subtilis and Enterococcus＂, and the both probiotics respectively. The duration of treatment was 1 month. Laboratory parameters were evaluated before treatment and thirtieth day after treatment, including cholesterol （TC）, triglyceride （TG）, high density lipoprotein cholesterol （HDL-C）, low density lipoprotein cholesterol（LDL-C）, alanine aminotransferase（ALT）, aspartate aminotransferase （AST）, fasting blood glucose （FPG）, serum high molecular weight adiponectin （HMW-APN） and serum TNFα. Meanwhile the faece sample was collected for routine test and bacterial culture. Liver ultrasound scan was done in all patients. Results In terms of blood lipids and blood glucose, each group improved after treatment with significant differences（P〈0.05）except for HDL-C. As for liver function, serum ALT and AST decreased after treatment in each group; especially in combined group C which were lower than those of control group [（33.7±7.6） U/L vs. （45.0±8.5） U/L; （22.0±1.6） U/L vs. （29.4±3.7） U/L; P〈0.05]. TNFα levels decreased after treatment in each group, in addition the values in combined group C was significantly lower than that of control group[（0.51 ± 0.27） μg/L vs. （0.82 ± 0.28） μg/L, P〈0.05]. Serum HMW-APN increased after treatment in each group, and the HMW-APN in combined C group was significantly higher than that of control group[（9.28 ± 3.72） μg/L vs. （7.87 ± 3.96）μg/L, P〈0.05].（5）After treatment, all groups showed improvement of fatty liver by ultrasound, but the difference between groups was not statistically significant.（6）Compared with before treatment, fecal flora in combined groups was all reduced （P〈0.01）, but it was comparable before and after treatment in control group. Conclusions Probiotics improve intestinal microecological system in NAFLD patients via inhibiting TNFα and enhancing adiponectin, possibly resulting in regulating blood glucose, lipid metabolism, and protecting liver injury from NAFLD.