微量量热法体外表征拉米夫定对肠道特征菌群的影响

Effects of lamivudine on growth of intestinal characteristic bacteria by microcalorimetry in vitro

采用微量量热法研究拉米夫定对3种肠道特征细菌青春双歧杆菌、痢疾志贺菌及大肠埃希菌生长代谢的影响。在不同给药剂量下,以表达功率时间曲线(热谱曲线)的特征参数生长速率常数(k)、热功率(p)、达峰时间(t)、发热量(Q)为指标,对拉米夫定影响肠道特征细菌生长代谢程度进行客观地量化评价。结果显示,拉米夫定对青春双歧杆菌的半数抑制率(IC50)为200μg·mL-1,对痢疾志贺菌的IC50大于3 000μg·mL-1,对大肠埃希菌的IC50大于6 000μg·mL-1。结果显示,拉米夫定对3种肠道特征菌群抑制效果呈现明显差异,其"敏感"程度依次为青春双歧杆菌>痢疾志贺菌>大肠埃希菌;研究提示长期口服拉夫米定可能破坏菌道菌群平衡,存在导致内毒素等增加、引发炎症、加速肝病病情恶化的潜在风险。

The study is aimed to investigate the effect of lamivudine on growth and metabolism of three intestinal characteristic bacteria （namely, Bifidobacterium adolescentis, Escherichia coli and Shigella dysenteriae）. The growth condition of the three bacteria was quantitatively evaluated by microcalorimetry with four characteristic parameters of the thermal power-time curves, including the growth rate constant （k）, thermal power （p）, time to peak （t） and calorific value （Q）. The results showed that the IC50 value of lamivudine on B. adolescentis was 200 μg·mL-1, and the IC50 values of lamivudine on S. dysenteriae and E. coli were higher than 3 000 μg·mL-1 and 6 000 μg·mL-1, respectively. Therefore, lamivudine made different inhibitory effects on the three bacteria, in which the B. adolescentis was most susceptible to lamivudine. This work showed that taking lamivudine chronically is likely to affect the balance of good flora in the intestinal tract, and might increase endotoxin release, leading to inflammation and disease progression in hepatopathy.