Sheen-Chen Shyr-Ming, Eng Hock-Liew, Hung Kuo-Sheng
Department of Surgery, College of Medicine, Chang Gung University, Chang Gung Memorial Hospital, Kaohsiung, 123 Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung Hsien, Taiwan.
World J Surg. 2004 Oct;28(10):967-70. doi: 10.1007/s00268-004-7354-z. Epub 2004 Sep 29.
Impaired immune function has long been documented in patients with obstructive jaundice, and those with jaundice due to extrahepatic biliary obstruction still experience a high rate of postoperative complications and death. Transforming growth factor-beta1 (TGFbeta1) appears to be an important regulator of both normal and pathologic conditions in the liver. Monocyte chemoattractant protein-1 (MCP-1) is an important mediator of monocyte recruitment to inflammatory sites. We hypothesize that obstructive jaundice may alter serum TGFbeta1 and MCP-1 expressions in the rat and that oral bile acid or glutamine (or both) can restore the altered serum TGFbeta1 and MCP-1 expression in rats with obstructive jaundice. Male Sprague-Dawley rats weighing 250 to 300 g were randomized to four groups (n = 10 in each group). Group 1 underwent a sham operation with oral normal saline administration. Group 2 underwent common bile duct ligation (CBDL) with oral normal saline administration. Group 3 underwent CBDL with oral bile acid replacement. Group 4 underwent CBDL with oral glutamine administration. Animals were sacrificed after 3 days (n = 5) and 7 days (n = 5), and blood samples were collected. Serum was obtained after centrifugation for measurement of TGFbeta1 and MCP-1 levels by an enzyme-linked immunosorbent assay. The serum TGFbeta1 level was significantly elevated (p = 0.006) 3 days after CBDL. Oral glutamine administration prevented this elevation, but oral bile acid replacement did not. The serum MCP-1 level showed similar changes. After 3 days of obstructive jaundice, the TGFbeta1 and MCP-1 levels were altered in the rat. Oral glutamine administration, not oral bile acid replacement, was able to prevent these alterations.
长期以来,阻塞性黄疸患者的免疫功能受损已被证实,而肝外胆管梗阻所致黄疸患者术后仍有较高的并发症发生率和死亡率。转化生长因子-β1(TGFβ1)似乎是肝脏正常和病理状态的重要调节因子。单核细胞趋化蛋白-1(MCP-1)是单核细胞募集至炎症部位的重要介质。我们推测,阻塞性黄疸可能会改变大鼠血清中TGFβ1和MCP-1的表达,而口服胆汁酸或谷氨酰胺(或两者)可恢复阻塞性黄疸大鼠血清中TGFβ1和MCP-1表达的改变。将体重250至300克的雄性Sprague-Dawley大鼠随机分为四组(每组n = 10)。第1组接受假手术并口服生理盐水。第2组接受胆总管结扎(CBDL)并口服生理盐水。第3组接受CBDL并口服胆汁酸替代物。第4组接受CBDL并口服谷氨酰胺。3天(n = 5)和7天(n = 5)后处死动物并采集血样。离心后获得血清,通过酶联免疫吸附测定法测量TGFβ1和MCP-1水平。CBDL后3天血清TGFβ1水平显著升高(p = 0.006)。口服谷氨酰胺可防止这种升高,但口服胆汁酸替代物则不能。血清MCP-1水平显示出类似变化。阻塞性黄疸3天后,大鼠体内TGFβ1和MCP-1水平发生改变。口服谷氨酰胺而非口服胆汁酸替代物能够预防这些改变。