University Medical School of Bari, 70124 Bari, Italy.
Eur J Clin Invest. 2009 Nov;39(11):986-92. doi: 10.1111/j.1365-2362.2009.02187.x. Epub 2009 Jul 28.
Proteins might act as pronucleating agents of cholesterol crystallization in bile. However, little is known about the redox status of biliary proteins in humans and their interaction with crystallization of biliary cholesterol.
Gallbladder biles were obtained at cholecystectomy from 86 symptomatic patients with either cholesterol gallstones (32 multiple and 32 solitary stones) or pigment stones (n = 22), and studied for protein redox status [carbonyl and sulfhydryl (PSH) concentrations], total lipid and protein levels and cholesterol saturation index (CSI). First appearance of cholesterol crystals in ultrafiltered bile (crystal observation time, COT) was studied with polarizing light microscopy during 21 days.
Patients with cholesterol stones had significantly shorter COT (3 days vs. >21 days, P < 0.05), higher CSI (149 +/- 10% vs. 97 +/- 7%, P < 0.05) and higher total biliary proteins (1.96 +/- 0.1 mg mL(-1) vs. 0.55 +/- 0.1 mg mL(-1), P < 0.05) than patients with pigment stones. Patients with cholesterol stones had significantly lower (P < 0.05) level of protein sulfhydryl concentrations (18 +/- 4 nmol mg(-1) protein vs. 49 +/- 16 nmol mg(-1) protein), while total lipid and carbonyl proteins concentrations were similar between cholesterol and pigment stone patients. Crystallization probability was influenced by the number/type of gallstones (multiple > solitary > pigment stones, P = 0.009) and total protein concentration (high > low levels, P = 0.004). COT was negatively correlated with total protein content (r = -0.45, P = 0.03).
Biles with cholesterol stones show high CSI and total protein concentration, and rapid COT, which is even faster in patients with multiple stones and high protein concentration. Low PSH levels in cholesterol stone patients point to a biochemical shift, potentially able to affect cholesterol crystallization.
蛋白质可能在胆汁胆固醇结晶中充当核前体。然而,人们对人类胆汁蛋白的氧化还原状态及其与胆汁胆固醇结晶的相互作用知之甚少。
在胆囊切除术时,从 86 例有症状的患者中获得胆囊胆汁,这些患者要么患有胆固醇胆结石(32 例多发结石和 32 例单发结石),要么患有色素结石(n=22),并研究其蛋白氧化还原状态[羰基和巯基(PSH)浓度]、总脂质和蛋白水平以及胆固醇饱和度指数(CSI)。在 21 天的时间内,通过偏光显微镜研究超滤液中胆固醇晶体的首次出现(晶体观察时间,COT)。
胆固醇结石患者的 COT 明显更短(3 天 vs. >21 天,P<0.05),CSI 更高(149±10% vs. 97±7%,P<0.05),总胆汁蛋白水平更高(1.96±0.1mg/mL vs. 0.55±0.1mg/mL,P<0.05),明显高于色素结石患者。胆固醇结石患者的蛋白巯基浓度明显较低(18±4nmol/mg 蛋白 vs. 49±16nmol/mg 蛋白,P<0.05),而胆固醇和色素结石患者的总脂质和羰基蛋白浓度相似。结晶概率受胆结石数量/类型(多发结石>单发结石>色素结石,P=0.009)和总蛋白浓度(高水平>低水平,P=0.004)的影响。COT 与总蛋白含量呈负相关(r=-0.45,P=0.03)。
胆固醇结石胆汁显示出高 CSI 和总蛋白浓度,以及快速的 COT,而多发结石和高蛋白浓度的患者 COT 更快。胆固醇结石患者的 PSH 水平较低,提示生化变化,可能影响胆固醇结晶。