Sagawa H, Tazuma S, Kajiyama G
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Am J Physiol. 1993 May;264(5 Pt 1):G835-9. doi: 10.1152/ajpgi.1993.264.5.G835.
Under physiological circumstances, cell membrane damage is not evident in biliary systems, despite the fact that hydrophobic bile salts are known to induce such damage by their detergent effects. The aim of this study was to determine the cytoprotective effects of liposomes and hydrophilic bile salts against hydrophobic bile salt-induced cell membrane damage, with the use of hemolysis of erythrocytes as a model of cytotoxicity. Washed human erythrocytes were incubated for 10, 30, 60, 90, and 120 min in buffered media (pH 7.45) containing increasing concentrations of different bile salts (1, 2.5, 5, 25, 50 mM). The cytotoxicity of the bile salts was found to be dose and time dependent and was correlated to the degree of the hydrophobicity of the bile salts as determined by the retention factor in reversed-phase high-performance liquid chromatography. Hydrophobic bile salt-induced hemolysis was reduced by liposomes and hydrophilic bile salts. Cytoprotection by liposomes was related to the degree of saturation of the fatty acyl chains, and cytoprotection by hydrophilic bile salts was related to their hydrophilicity. These in vitro findings indicate that vesicles may play a role in protection against cell membrane damage by hydrophobic bile salts in biliary systems and that such damage may be caused by an imbalance between hydrophobic and hydrophilic bile salts.
在生理情况下,尽管已知疏水性胆盐可通过其去污剂作用诱导细胞膜损伤,但在胆道系统中细胞膜损伤并不明显。本研究的目的是利用红细胞溶血作为细胞毒性模型,确定脂质体和亲水性胆盐对疏水性胆盐诱导的细胞膜损伤的细胞保护作用。将洗涤后的人红细胞在含有不同胆盐浓度逐渐增加(1、2.5、5、25、50 mM)的缓冲介质(pH 7.45)中孵育10、30、60、90和120分钟。发现胆盐的细胞毒性具有剂量和时间依赖性,并且与通过反相高效液相色谱中的保留因子确定的胆盐疏水性程度相关。脂质体和亲水性胆盐可减少疏水性胆盐诱导的溶血。脂质体的细胞保护作用与脂肪酰链的饱和度有关,亲水性胆盐的细胞保护作用与其亲水性有关。这些体外研究结果表明,囊泡可能在保护胆道系统免受疏水性胆盐引起的细胞膜损伤中发挥作用,并且这种损伤可能是由疏水性和亲水性胆盐之间的失衡引起的。