Aouad K, Calmus Y, Nordlinger B, Myara A, Weill B, Poupon R
INSERM U 181, Hôpital Saint-Antoine, Paris, France.
Eur J Clin Invest. 1996 Jan;26(1):45-8. doi: 10.1046/j.1365-2362.1996.95240.x.
Cell-mediated immunity is impaired during cholestasis. The aim of this study was to evaluate in vivo the effects on this immune defect of high serum levels of endotoxin and bile acids. Heterotopic cardiac allotransplantations were performed in the DA/Lewis rat combination. Cholestasis, induced by ligation/section of the common bile duct, was responsible for a significant delay in the rejection time (16 +/- 0.5 vs. 7.1 +/- 0.4 days in controls, P < 0.01). Elimination of Gram-negative intestinal bacteria from cholestatic rats by a vancocin/colimycin/tobramycin (VCT) mixture induced a significant reduction in endotoxin levels and a reduction in rejection times (9.5 +/- 1.0 days, P < 0.01) that remained, however, significantly longer than those of controls (P < 0.05). Oral administration of chenodeoxycholic acid in non-cholestatic rats significantly enhanced the serum concentration of total bile acids (60.6 +/- 15.3 mumol L(-1) vs. 17.4 +/- 1.9 mol L(-1) in controls, P < 0.01) and postponed allograft rejection (10.7 +/- 0.6 days, P < 0.01 vs. controls). These data suggest that increased endotoxin level and serum bile acid concentration may play a role in the immunosuppressive effect of cholestasis.
胆汁淤积期间细胞介导的免疫功能受损。本研究的目的是在体内评估高血清水平的内毒素和胆汁酸对这种免疫缺陷的影响。在DA/刘易斯大鼠组合中进行异位心脏同种异体移植。通过结扎/切断胆总管诱导的胆汁淤积导致排斥反应时间显著延迟（对照组为7.1±0.4天，胆汁淤积组为16±0.5天，P<0.01）。用万古霉素/黏菌素/妥布霉素（VCT）混合物清除胆汁淤积大鼠的革兰氏阴性肠道细菌可导致内毒素水平显著降低，排斥反应时间缩短（9.5±1.0天，P<0.01），但仍显著长于对照组（P<0.05）。在非胆汁淤积大鼠中口服鹅去氧胆酸可显著提高总胆汁酸的血清浓度（对照组为17.4±1.9μmol L-1，给药组为60.6±15.3μmol L-1，P<0.01），并延迟同种异体移植排斥反应（10.7±0.6天，与对照组相比P<0.01）。这些数据表明，内毒素水平升高和血清胆汁酸浓度可能在胆汁淤积的免疫抑制作用中起作用。
