Magnolol Pretreatment Prevents Sepsis-Induced Intestinal Dysmotility by Maintaining Functional Interstitial Cells of Cajal
Magnolol Pretreatment Prevents Sepsis-Induced Intestinal Dysmotility by Maintaining Functional Interstitial Cells of Cajal
复制标题
厚朴酚预处理通过维持 Cajal 间质细胞的功能来预防脓毒症引起的肠动力障碍
DOI：
10.1007/s10753-013-9617-z
复制
发表时间：
2013-08-01
期刊：
影响因子：
5.1
通讯作者：
Wang, Bao-en
中科院分区：
文献类型：
--
作者：
Miao, Bin;Zhang, Shuwen;Wang, Bao-en
本研究旨在探讨厚朴酚预防脂多糖(LPS)诱导的小鼠脓毒症运动障碍的机制。尾静脉注射脂多糖(4 mg/kg体重)诱导大鼠脓毒症。动物被分成三组：厚朴酚治疗败血症组、安慰剂治疗败血症组和对照组。内毒素注射后12h测定肠传输和环状平滑肌收缩，免疫细胞化学方法观察Cajal间质细胞的形态。用Western印迹法检测干细胞因子(SCF)的表达和c-kit的磷酸化，用RT-PCR法检测诱导型一氧化氮合酶(INOS)的mRNA水平。用商品化试剂盒检测一氧化氮(NO)含量、超氧化物歧化酶(SOD)活性和丙二醛(MDA)浓度。内毒素治疗组大鼠的肠道转运和肌肉收缩能力明显低于对照组。免疫细胞化学实验显示，与对照组相比，内毒素处理组ICCs总数、ICC突起总长度和平均长度均显著减少。在内毒素处理的动物中，厚朴酚预处理显著加速肠道传输，增加环行肌收缩，并防止ICC的形态改变。与对照组相比，内毒素处理组大鼠肝组织中c-kit的磷酸化水平和SCF的表达均显著下调。厚朴酚预处理可预防脓毒症引起的内毒素处理动物c-kit磷酸化和SCF表达的降低。厚朴酚预处理可预防脓毒症引起的内毒素诱导的NO浓度、iNOS表达和MDA浓度的升高，以及SOD活性的降低。我们的结果提示，厚朴酚治疗可通过调节SCF/c-kit和NO信号来维持ICCs的功能，从而预防脓毒症引起的肠道运动障碍。
The purpose of this study was to investigate the mechanism by which magnolol treatment prevents lipopolysaccharide (LPS)-induced septic dysmotility in mice. Sepsis was induced by intravenous tail vein injection of LPS (4 mg/kg body weight). Animals were divided into three groups: the magnolol-treated septic group, the placebo-treated septic group, and the control group. Intestinal transit and circular smooth muscle contraction were measured 12 h after LPS injection, and immunocytochemisty was performed to study the morphology of interstitial cells of Cajal (ICCs). Stem cell factor (SCF) expression and c-kit phosphorylation were determined by Western blot analysis, and the mRNA levels of inducible NO synthase (iNOS) were determined by RT-PCR. Nitric oxide (NO) content, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) concentration were detected using commercial kits. Intestinal transit and muscular contractility were significantly lower in the LPS-treated group than in the control group. Immunocytochemical experiments showed that the total number of ICCs, and the total and average lengths of the ICC processes were significantly decreased in the LPS-treated group compared with those in the control group. In LPS-treated animals, magnolol pretreatment significantly accelerated intestinal transit, increased circular muscle contraction, and prevented ICC morphology changes. Phosphorylation of c-kit and expression of SCF were significantly downregulated in LPS-treated animals compared with control animals. Magnolol pretreatment prevented sepsis-induced decreases in c-kit phosphorylation and SCF expression in LPS-treated animals. Magnolol pretreatment prevented the sepsis-induced increase in NO concentration, iNOS expression, and MDA concentration, and decrease in SOD activity in LPS-treated animals. Our results suggest that magnolol treatment prevents sepsis-induced intestinal dysmotility by regulating SCF/c-kit and NO signaling to maintain functional ICCs.