Miao Hui-Lai, Qiu Zhi-Dong, Hao Fu-Long, Bi Yong-Hui, Li Ming-Yi, Chen Ming, Chen Nian-Ping, Zhou Fei
Hui-Lai Miao, Zhi-Dong Qiu, Ming-Yi Li, Ming Chen, Nian-Ping Chen, Department of Hepatobiliary Surgery, the Affiliated Hospital of Guangdong Medical College, Zhanjing 524001, Guangdong Province, China.
World J Hepatol. 2010 Jun 27;2(6):233-8. doi: 10.4254/wjh.v2.i6.233.
To investigate the expression of myeloid differentiation protein-2 (MD-2), MD-2B (a splicing isoform of MD-2 that can block Toll-like receptor 4 (TLR4)/MD-2 LPS-mediated signal transduction) and TLR4 in the liver of acute cholangitis rats.
Male Sprague-Dawley rats (SPF level) were randomly divided into four groups: (A) sham-operated group; (B) simple common bile duct ligation group; (C) acute cholangitis group; and (D) acute cholangitis anti-TLR4 intervention group (n = 25 per group). Rat liver tissue samples were used to detect TLR4, MD-2 and MD-2B mRNA expression by fluorescence quantitative PCR in parallel with pathological changes.
In acute cholangitis, liver TLR4 and MD-2 mRNA expression levels at 6, 12, 24, 48 and 72 h were gradually up-regulated but MD-2B mRNA expression gradually down-regulated (P < 0.05). After TLR4 antibody treatment, TLR4 and MD-2 mRNA expression were lower compared with the acute cholangitis group (P < 0.05). However, MD-2B mRNA expression was higher than in the acute cholangitis group (P < 0.05). MD-2 and TLR4 mRNA expressions were positively correlated (r = 0.94981, P < 0.05) and MD-2B mRNA expression was negatively correlated with MD-2 and TLR4 mRNA (r = -0.89031, -0.88997, P < 0.05).
In acute cholangitis, MD-2 plays an important role in the process of TLR4- mediated inflammatory response to liver injury while MD-2B plays a negative regulatory role.
研究急性胆管炎大鼠肝脏中髓样分化蛋白2(MD-2)、MD-2B(MD-2的一种剪接异构体,可阻断Toll样受体4(TLR4)/MD-2脂多糖介导的信号转导)及TLR4的表达。
将雄性Sprague-Dawley大鼠(无特定病原体级)随机分为四组:(A)假手术组;(B)单纯胆总管结扎组;(C)急性胆管炎组;(D)急性胆管炎抗TLR4干预组(每组n = 25)。取大鼠肝脏组织样本,采用荧光定量PCR检测TLR4、MD-2和MD-2B mRNA表达,并观察病理变化。
急性胆管炎时,6、12、24、48和72 h肝脏TLR4和MD-2 mRNA表达水平逐渐上调,但MD-2B mRNA表达逐渐下调(P < 0.05)。TLR4抗体处理后,与急性胆管炎组相比,TLR4和MD-2 mRNA表达降低(P < 0.05)。然而,MD-2B mRNA表达高于急性胆管炎组(P < 0.05)。MD-2与TLR4 mRNA表达呈正相关(r = 0.94981,P < 0.05),MD-2B mRNA表达与MD-2和TLR4 mRNA呈负相关(r = -0.89031,-0.88997,P < 0.05)。
在急性胆管炎中,MD-2在TLR4介导的肝脏损伤炎症反应过程中起重要作用,而MD-2B起负性调节作用。