Jüngst C, Sreejayan N, Eder M I, von Stillfried N, Zündt B, Spelsberg F W, Kullak-Ublick G A, Jüngst D, von Ritter C
University Hospital, Zurich, Switzerland.
Eur J Clin Invest. 2007 Sep;37(9):731-6. doi: 10.1111/j.1365-2362.2007.01853.x.
Chronic inflammation of the gallbladder wall and mucin hypersecretion are considered to be important factors in the pathogenesis of cholesterol gallstone disease. The aim of the study was to compare mucin concentration and mucin secretagogue activity with lipid peroxidation in gallbladder bile of patients with cholesterol or pigment stones.
We studied mucin concentration and, as a marker of lipid peroxidation, malondialdehyde concentration in 11 rapid (1 to 3 days) and eight non-nucleating (> 21 days) gallbladder biles of patients with cholesterol or pigment stones. Furthermore, the mucin secretagogue activity of rapid and non-nucleating gallbladder biles, as well as 1-5 micromol L(-1) malondialdehyde on cultured gallbladder epithelial cells, was determined.
Our data show an increased malondialdehyde (7.2 +/- 1.8 vs. 3.8 +/- 0.5 micromol L(-1), P = 0.01) and mucin concentration (0.9 +/- 0.09 vs. 0.41 +/- 0.03 mg mL(-1), P = 0.01) and an increased mucin secretagogue activity (2.0 +/- 0.5 vs. 1.1 +/- 0.3 mucin secretion/control, P = 0.04) and cholesterol saturation index (1.2 +/- 0.1 vs. 08 +/- 0.1, P = 0.04) in rapid as compared to non-nucleating gallbladder biles. Malondialdehyde stimulated mucin secretion of cultured gallbladder epithelial cells in a concentration dependent manner.
Our results support a promoting effect of gallbladder mucin hypersecretion by lipid peroxidation leading to rapid formation of cholesterol crystals in gallbladder bile. These findings suggest that besides hypersecretion of cholesterol in bile, chronic inflammation of the gallbladder wall is implicated in the pathogenesis of cholesterol gallstone disease.
胆囊壁的慢性炎症和粘蛋白分泌过多被认为是胆固醇结石病发病机制中的重要因素。本研究的目的是比较胆固醇结石或色素结石患者胆囊胆汁中粘蛋白浓度、粘蛋白促分泌活性与脂质过氧化情况。
我们研究了11例胆固醇结石或色素结石患者快速(1至3天)胆囊胆汁和8例非成核(>21天)胆囊胆汁中的粘蛋白浓度,以及作为脂质过氧化标志物的丙二醛浓度。此外,还测定了快速和非成核胆囊胆汁以及1-5微摩尔/升丙二醛对培养的胆囊上皮细胞的粘蛋白促分泌活性。
我们的数据显示,与非成核胆囊胆汁相比,快速胆囊胆汁中的丙二醛浓度升高(7.2±1.8对3.8±0.5微摩尔/升,P = 0.01)、粘蛋白浓度升高(0.9±0.09对0.41±0.03毫克/毫升,P = 0.01)、粘蛋白促分泌活性升高(2.0±0.5对1.1±0.3粘蛋白分泌/对照,P = 0.04)以及胆固醇饱和指数升高(1.2±0.1对0.8±0.1,P = 0.04)。丙二醛以浓度依赖的方式刺激培养的胆囊上皮细胞分泌粘蛋白。
我们的结果支持脂质过氧化对胆囊粘蛋白分泌过多具有促进作用,从而导致胆囊胆汁中胆固醇晶体快速形成。这些发现表明,除了胆汁中胆固醇分泌过多外,胆囊壁的慢性炎症也与胆固醇结石病的发病机制有关。