急性肝衰竭大鼠肠道菌群和内毒素的动态研究

Dynamic variability of intestinal flora and endotoxin in rat with fulminate hepatic failure

目的 研究急性肝衰竭大鼠肠道菌群及内毒素的动态变化。 方法 腹腔注射半乳糖胺建立急性肝衰竭大鼠模型。40只SD大鼠随机分为A组(对照组)10只;B组12只,C组18只(均为肝衰竭大鼠)。实验开始时(A组)、造模后24 h(B组)和48 h(C组)分别处死各组大鼠并检测肝功能,定性、定量分析空肠、回肠及结肠菌群,定量测定门静脉、右心室血,回肠及结肠内毒素。 结果 肝功能检测显示:B组大鼠的肝脏损伤最为严重;与B组相比,C组大鼠的肝功能开始好转。肠道菌群分析显示:B组大鼠肠道内肠杆菌科细菌显著增加(空肠、回肠间,P<0.01;结肠间,P<0.05)、乳酸杆菌下降(P<0.01);与B组相比,C组空肠和结肠内的肠杆菌科细菌出现下降(P<0.05)、乳酸杆菌增加,以空肠为显著(P<0.05)。内毒素测定表明B组回肠内毒素增加(P<0.05);C组空肠和回肠内毒素继续增高与对照组差异有显著性(P<0.01);门静脉内内毒素在B组最高,与A、C两组比较差异有显著性(P<0.01)。 结论 急性肝衰竭大鼠肠道存在菌群失调、肠杆菌科细菌过度生长,菌群失调程度与肝损伤程度有关;肠道菌群失调伴有回肠和结肠内内毒素升高;

Objective To investigate the dynamic variability of intestinal flora and endotoxins in rats with fulminate hepatic failure. Methods Establishing the fulminate hepatic failure models by intraperitoneal injection of Galactosamine. Forty Sprague-Dawley rats were divided into three groups: group A (n = 10) were killed at the beginning of the experiment as control; while Group B (n = 12) and C (n = 18), the fulminate hepatic failure models, were killed 24 and 48 hours respectively after successful induction. Then, the contents of the jejunum, ileum and colon descendents were collected and a quantitative analysis was made about intestinal flora. Meanwhile, the concentrations of endotoxin in portal vein and right ventricle were determined and so were those in contents of ileums and colons. Results Our experiments showed that the livers of rats in group B were injured most seriously among three groups, and a minor recovery of hepatic function was observed in group C with the decrease of total bile acids (P < 0.05). Analysis on intestinal flora show: the intestiral enterobacteriacea increase and the lactobacillus decrease in group B (P < 0.01 in jejunum and ileum and P < 0.05 in colon). The comparisons between group C and B showed that the enterobacteriacea in the former decreased in both jejunum and colon (P < 0.05) while the number of lactobacillus recovered in the jejunum of group C (P < 0.05). Quantitative analysis on endotoxins showed that the ileum endotoxin increased in group B (P < 0.05) and in group C, endotoxins in ileam and colons also increased (vs. control, P < 0.01); portal endotoxin in group B showed higher level . than that in group A and C (P < 0.01). Conclusions The alteration of intestinal flora was observed in fulminate hepatic failure rats. Abnormal intestinal flora might lead to incline of endotoxin in ileum, colon and portal vein, while the recovery of normal intestinal flora would decrease the level of portal endotoxin.