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目的建立大鼠肝性脑病及FMT细菌模型,确定粪便细菌移植对肝性脑病大鼠肝功能及血氨的影响,初步了解粪便细菌移植(fecal microbiota transplantation,FMT)的临床意义。方法选择32只SD大鼠,采用CCL4+酒精的方法建立大鼠肝性脑病模型及肠道埋管,分为4组(A组:正常对照组;B组:肝性脑病模型组;C组:益生菌组;D组:FMT组),对C组进行益生菌移植,200μL/d(200μL益生菌溶液中含益生菌2.7×10~9),持续2周;对D组进行FMT移植,200μL/d(200μL粪便细菌溶液中含粪便细菌2.7×10~9),持续2周。记录大鼠一般生存情况及大便情况,对移植前后体重进行比较,测定移植前、后肝功能(ALT、AST、ALB、TB及DB)和门静脉及尾静脉血氨。结果所有实验大鼠均未出现死亡;粪便细菌移植后肝性脑病大鼠体重移植前明显增加[D组移植前(225.18±14.81)g,移植后2周(266.83±33.40)g,P<0.05];移植后大鼠肝功能较前明显好转[移植后2周ALT:D组与B组分别为(610.49±4.98)U/L和(990.07±4.80)U/L,P<0.05;AST:D组与B组分别为(72.46±4.42)U/L和(101.58±2.19)U/L,P<0.05;ALB:D组与B组比较ALB明显上升,分别为(24.48±0.12)g/L和(17.53±0.53)g/L,P<0.05;TB:D组为(13.45±0.77)μmol/L,B组为(27.20±0.77)μmol/L,P<0.05;DB:D组为(10.04±0.09)μmol/L,B组为(16.04±0.51)μmol/L,P<0.05];门静脉及尾静脉血氨较移植前明显降低[D组门静脉及尾静脉血氨分别为(26.26±0.30)μmol/L和(23.10±0.35)μmol/L,B组分别为(36.28±1.32)μmol/L和(32.90±0.35)μmol/L,P<0.05]。结论对大鼠进行人体粪便细菌移植是可行的;粪便细菌移植可改善肝性脑病大鼠的肝功能,降低血氨。
Objective To establish rat model of hepatic encephalopathy and FMT and determine the effect of stool bacterial transplantation on liver function and blood ammonia in rats with hepatic encephalopathy and to understand the clinical significance of fecal microbiota transplantation (FMT). Methods 32 SD rats were selected. CCL4 + alcohol was used to establish model of hepatic encephalopathy in rats and intestinal tubes were divided into 4 groups (group A: normal control group, group B: hepatic encephalopathy model group, group C: Probiotics group; group D: FMT group), probiotics transplantation group C, 200μL / d (200μL probiotic solution containing probiotics 2.7 × 10 ~ 9) for 2 weeks; group D FMT transplantation, 200μL / d (200μL faecal bacteria solution containing stool bacteria 2.7 × 10 ~ 9) for 2 weeks. The general survival condition and stool condition of rats were recorded. The body weight before and after transplantation was compared. The liver function (ALT, AST, ALB, TB and DB) and blood ammonia in the portal vein and tail vein were measured before and after transplantation. Results All rats died of hepatic encephalopathy after transplanted with bacterial stool. The weight of rats with hepatic encephalopathy after transplanted with stool bacterial significantly increased (225.18 ± 14.81 g, D 2, 266.83 ± 33.40 g, P <0.05 (P <0.05). The liver function of rats after transplanted was significantly improved compared with that before transplantation. The levels of ALT in the two weeks after transplantation were (610.49 ± 4.98) U / L and (990.07 ± 4.80) U / The ALB in group D and group B were (72.46 ± 4.42) U / L and (101.58 ± 2.19) U / L respectively, P <0.05; ALB in group D was significantly higher than that in group B (24.48 ± 0.12) g / L and (17.53 ± 0.53) g / L respectively, P <0.05; while the level of TB in group D was (13.45 ± 0.77) μmol / L in group B and (27.20 ± 0.77) μmol / L in group B (10.04 ± 0.09) μmol / L in group B and (16.04 ± 0.51) μmol / L in group B, P <0.05]. The blood ammonia in portal vein and caudal vein was significantly lower than that before transplantation ± 0.30) μmol / L and (23.10 ± 0.35) μmol / L in group B, and (36.28 ± 1.32) μmol / L and (32.90 ± 0.35) μmol / L in group B, respectively. Conclusion Bacterial transplantation of human feces in rats is feasible. Stool bacterial transplantation can improve hepatic function and blood ammonia in rats with hepatic encephalopathy.