Impaired cytoprotective function of muscle in human gallbladders with cholesterol stones.
Impaired cytoprotective function of muscle in human gallbladders with cholesterol stones.
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DOI：
10.1152/ajpgi.00261.2004
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发表时间：
2005-03
期刊：
影响因子：
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通讯作者：
Zuoliang Xiao;J. Amaral;P. Biancani;J. Behar
中科院分区：
文献类型：
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作者：
Zuoliang Xiao;J. Amaral;P. Biancani;J. Behar
急性胆囊炎发生于胆汁胆固醇过高的胆囊（GB）。细胞膜Ch含量的增加会影响细胞膜功能，并可能影响参与抗急性炎症细胞保护的PGE(2)受体。本研究旨在确定含有Ch的产石胆汁是否会影响PGE(2)的细胞保护反应。酶消化法获得了患有胆固醇结石（ChS）或色素结石（PS）的人GB的肌肉细胞。采用放射免疫法测定PGE(2)水平，分光光度法测定超氧化物歧化酶（SOD）和过氧化氢酶活性。PS肌肉细胞对H(2)O(2)的响应收缩率为14 +/- 0.3%，与正常对照无显著差异，富Ch脂质体培养后收缩率降低（P < 0.05），使质膜中Ch含量增加。H(2)O(2)诱导的肌细胞收缩率仅为9.2 +/- 1.3%，经无Ch脂质体处理去除质膜中的Ch后，H(2)O(2)诱导的收缩率为14 +/- 0.2% （P < 0.01）。H(2)O(2)可使患有ChS和PS的gb肌肉细胞的脂质过氧化水平和PGE(2)含量相似地升高，但与PS相比，患有ChS的gb肌肉细胞的SOD和过氧化氢酶活性显著降低，PGE(2)受体的结合能力也显著低于患有PS的gb肌肉细胞。尽管细胞中PGE水平正常升高，但患有ChS的GBs肌肉细胞对活性氧的细胞保护反应降低(2)。这种受损的细胞保护反应可能是由于PGE(2)受体功能障碍，结合能力下降，导致质膜中过量的Ch水平。
Acute cholecystitis develops in gallbladders (GB) with excessive bile cholesterol (Ch). Increased membrane Ch content affects membrane function and may affect PGE(2) receptors involved in the cytoprotection against acute inflammation. This study was aimed at determining whether the cytoprotective response to PGE(2) is affected by lithogenic bile with Ch. Muscle cells from human GB with cholesterol stones (ChS) or pigment stones (PS) were obtained by enzymatic digestion. PGE(2) levels were measured by radioimmunoassay, and activities of superoxide dismutase (SOD) and catalase were assayed by spectrophotometry. The contraction in response to H(2)O(2) in muscle cells from PS was 14 +/- 0.3%, not different from normal controls, and decreased after the cells were incubated with Ch-rich liposomes (P < 0.05), which increase the Ch content in the plasma membranes. In muscle cells from GB with ChS, H(2)O(2)-induced contraction was only 9.2 +/- 1.3% and increased to 14 +/- 0.2% after Ch-free liposome treatment to remove Ch from the plasma membranes (P < 0.01). H(2)O(2) caused a similar increase in the levels of lipid peroxidation and PGE(2) content in muscle cells from GBs with ChS and PS. However, the activities of SOD and catalase were significantly lower in muscle cells from GBs with ChS compared with those with PS. The binding capacity of PGE(2) receptors was also significantly lower in muscle cells from GBs with ChS compared with those with PS. In conclusion, the cytoprotective response to reactive oxygen species is reduced in muscle cells from GBs with ChS despite a normal increase in the cellular levels of PGE(2). This impaired cytoprotective response may be due to a dysfunction of PGE(2) receptors with decreased binding capacity resulting from excessive Ch levels in the plasma membrane.