不同治疗方案对慢性乙型重型肝炎肠道菌群和血浆内毒素的影响

Effects of different treatments on microflora and plasma endotoxin in patients with chronic severe hepatitis B

目的研究不同治疗方案对慢性乙型重型肝炎患者肠道菌群和血浆内毒素的影响。方法纳入慢性乙型重型肝炎患者127例,分为A、B、C三组。A组(63例)患者口服双歧杆菌乳杆菌三联活菌片,B组(32例)患者口服双歧杆菌乳杆菌三联活菌片+乳果糖,C组(32例)患者口服双歧杆菌乳杆菌三联活菌片+乳果糖灌肠。治疗前及治疗第5、10、15、20天,分别检测三组患者大便肠球菌、酵母菌、双歧杆菌数量以及血浆内毒素水平。结果①治疗10天时三组患者双歧杆菌数量较治疗前均显著升高(均P<0.001);20天时的双歧杆菌数量与治疗10天时比较,A组无明显变化(P=0.318),B组和C组均明显减少(均P<0.001)。②治疗20天时,A、B组肠球菌数量与治疗前比较无明显变化(P=0.674和P=0.452),C组患者肠球菌明显升高(P<0.001);A组酵母菌与治疗前比较无明显变化(P=0.636),B、C组患者酵母菌均升高(P=0.036和P<0.001)。③A组患者在治疗第15天,B、C组患者在治疗第10天血浆内毒素下降至最低值,分别为(184.48±69.56)、(152.71±32.44)和(122.71±32.61)EU/L,三组患者血浆内毒素较治疗前均有显著降低(P=0.017、P<0.001和P<0.001),并且C组患者血浆内毒素明显低于A、B组(P<0.001);在治疗的第20天,B、C组患者血浆内毒素又明显升高(均P<0.001),而A组无明显变化(P=0.484)。结论单纯口服双歧杆菌乳杆菌三联活菌片可以调节肠道菌群,降低血浆内毒素,但作用轻微。口服双歧杆菌乳杆菌三联活菌片联合乳果糖口服或灌肠可显著降低血浆内毒素水平,但容易出现新的菌群失调,进而加重内毒素血症。乳果糖灌肠方式使药物作用更直接,但肠道黏膜损伤更大,对肠道菌群及内毒素水平影响更明显、迅速。

Objective To investigate the effects of different treatments on mieroflora and plasma endotoxin in patients with chronic severe hepatitis patients B. Methods One hundred and twenty-seven patients with chronic severe hepatitis B were randomly divided into A, B and C groups. The group A （n = 63 ） was orally given intestinal probiotics. The group B （n = 32 ） was administrated with intestinal probioties plus oral lactulose while the group C （ n = 32） with intestinal probiotics plus laetulose enema. The number of entero- coccus ,yeast,bifidobaeteria and plasma endotoxin was determined before and on 5th, 10th, 15th and 20th day of treatments. Results （1）On the 10th day of treatments, the number of bifidobaeteria was significantly increased in all the three groups when compared to treat- ment before（ all P 〈 0. 001 ）. However,the bacterial was significantly decreased in the group B and C on the 20th clay when compared to that on the 10th day （P 〈 0. 001 ） although there was no significant difference in the group A （P = 0. 318 ）. （2）On the 20th day of treat- ment, no significant difference in the number of enterococeus was found in the groups A and B （ P = 0. 674 and P = 0. 452,respective- ly） while it was significantly elevated in the group C （P 〈 0. 001 ） when compared to treatment before. At the same time, the number of yeast had no significant changes in the group A （P = 0. 636 ） while it was significantly increased in the groups B and C （P = 0. 036 and 〈 0. 001 ,respectively）. （3）The plasma endotoxin reached the lowest value on the 15th day in the group A（ 184. 48±69. 56 EU/L） and on the 10th clay in the groups B（ 152. 71± 32. 44 EU/L） and C（ 122. 71± 32. 61 EU/L）. Compared to that of treatment before the changes were statistically different（ P = 0. 017, 〈 0. 001 and 〈 0. 001, respectively）. On the 20th day of treatment, no significant chan- ges was found in the group A （P = 0. 484 ） but increased again in the group B and C （P 〈 0. 001 ）. Conclusion Single intestinal pro- biotics can slightly regulate the intestinal flora and reduce the plasma endotoxin. Intestinal probiotics combined with oral or enema lactu- lose can further reduce the level of plasma endotoxin. However,it may induce new bacterium maladjustment and result in aggravation of endotoxemia. Moreover, lactulose enema was more direct but mueosal injury of intestinal was bigger, although effect on mieroflora and endotoxin was more obvious and quick.