Sawa Hidehiro, Ueda Takashi, Takeyama Yoshifumi, Yasuda Takeo, Shinzeki Makoto, Nakajima Takahiro, Kuroda Yoshikazu
Department of Gastroenterological Surgery, Kobe University Graduate School of Medical Sciences, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Surg Today. 2007;37(10):867-73. doi: 10.1007/s00595-007-3520-x. Epub 2007 Sep 26.
Multiple organ dysfunction and infection are major contributors to the high mortality associated with severe acute pancreatitis (SAP). Toll-like receptor 4 (TLR4) recognizes the lipopolysaccharide of gram-negative bacilli and is involved in inflammatory response and host defense. We examined the effects of TLR4-deficiency in SAP in mice.
Closed duodenal loop-induced pancreatitis was induced in C3H/HeN (wild-type) and C3H/HeJ (TLR4-deficient) mice. We compared the severity of pancreatitis, liver and kidney dysfunction, and bacterial translocation to the pancreas between the two types of mice 12 h after the induction of SAP.
The severity of pancreatitis was similar in the two types of mice. The TLR4-deficient mice had significantly lower serum levels of aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine; significantly lower serum levels of interleukin-1 and tumor necrosis factor; reduced apoptosis of the liver and kidney; and a significantly higher rate of positive gram-negative bacterial cultures of the pancreas. TLR4 protein expression in the liver, kidney, and small intestine was increased 4 h after the induction of SAP, and decreased 12 h after the induction of SAP.
TLR4 is implicated in the mechanism of organ dysfunction and bacterial translocation in SAP, and TLR4 may trigger the inflammatory response and function defensively against infection.
多器官功能障碍和感染是导致重症急性胰腺炎（SAP）高死亡率的主要因素。Toll样受体4（TLR4）可识别革兰氏阴性杆菌的脂多糖，并参与炎症反应和宿主防御。我们研究了TLR4缺陷对小鼠SAP的影响。
在C3H/HeN（野生型）和C3H/HeJ（TLR4缺陷型）小鼠中诱导闭合十二指肠袢性胰腺炎。我们比较了诱导SAP后12小时两种小鼠之间胰腺炎的严重程度、肝肾功能障碍以及胰腺细菌移位情况。
两种小鼠胰腺炎的严重程度相似。TLR4缺陷型小鼠血清天冬氨酸转氨酶、丙氨酸转氨酶、血尿素氮和肌酐水平显著降低；血清白细胞介素-1和肿瘤坏死因子水平显著降低；肝肾细胞凋亡减少；胰腺革兰氏阴性菌培养阳性率显著升高。诱导SAP后4小时，肝、肾和小肠中TLR4蛋白表达增加，诱导SAP后12小时表达降低。
TLR4参与了SAP中器官功能障碍和细菌移位的机制，并且TLR4可能触发炎症反应并对感染发挥防御作用。
