Intensive Care Unit, Zhejiang Provincial People's Hospital, NO. 158, Shangtang Road, Hangzhou 310014, China.
Intensive Care Unit, Yanpu Hospital, Tongji University, NO. 450, Tengyue Road, Shanghai 200090, China.
Biomed Pharmacother. 2017 Feb;86:669-676. doi: 10.1016/j.biopha.2016.12.026. Epub 2016 Dec 27.
Sepsis causes nutritional substrate malabsorption; hence, preventing gut barrier problems and improving the nutritional status in sepsis is a compelling issue.
We tested whether ghrelin administration affects peptide transporter 1 (PepT1) activity in the intestinal epithelium of rats with sepsis.
Sixty male Sprague-Dawley rats were randomly divided into sham-operated, sepsis, and ghrelin-treated groups. The cecum of sham-operated rats was separated after laparotomy without ligation and perforation. Sepsis group rats underwent cecal ligation and puncture (CLP). Mucosal specimens were used for immunohistochemstry, real-time PCR, and western blotting to detect PepT1 distribution, and mRNA and protein expression levels, respectively. TNF-α, IL-1β, and ghrelin levels were estimated in serum and intestinal mucosal tissue by ELISA. High-performance liquid chromatography was used to measure PepT1 uptake by the epithelial cells. Moreover, survival, body weight, and food intake of the rats were recorded during the 7-day treatment period.
All rats in the sham-operated group survived, and 80% of rats in the sepsis group died within 7d of CLP. Treatment with ghrelin attenuated the CLP-induced body weight loss, intestine mucosa damage, and the survival rate was better. In addition, ghrelin attenuated increases in TNF-α and IL-1β production. The expressions of PepT1 mRNA and protein were higher in ghrelin-treated group rats than in sepsis rats. Moreover, the uptake function of PepT1 was better in ghrelin-treated group rats.
Ghrelin treatment can reduce the inflammatory response and greatly upregulate the physiological function of PepT1 in intestinal epithelial cells of rats with sepsis.
脓毒症导致营养底物吸收不良；因此，预防肠道屏障问题并改善脓毒症患者的营养状况是一个紧迫的问题。
我们测试了给予胃饥饿素是否会影响脓毒症大鼠肠上皮细胞中的肽转运蛋白 1（PepT1）活性。
60 只雄性 Sprague-Dawley 大鼠随机分为假手术、脓毒症和胃饥饿素治疗组。假手术大鼠在剖腹手术后分离盲肠而不结扎和穿孔。脓毒症组大鼠进行盲肠结扎和穿孔（CLP）。使用免疫组织化学、实时 PCR 和 Western blot 检测 PepT1 分布以及 mRNA 和蛋白表达水平，分别用于粘膜标本。通过 ELISA 估计血清和肠粘膜组织中的 TNF-α、IL-1β 和胃饥饿素水平。使用高效液相色谱法测量上皮细胞对 PepT1 的摄取。此外，在 7 天治疗期间记录大鼠的存活、体重和食物摄入。
假手术组所有大鼠均存活，CLP 后 7d 内 80%的脓毒症组大鼠死亡。胃饥饿素治疗减轻了 CLP 引起的体重减轻、肠黏膜损伤，并且生存率更好。此外，胃饥饿素减轻了 TNF-α和 IL-1β 的产生增加。胃饥饿素治疗组大鼠 PepT1 mRNA 和蛋白的表达高于脓毒症组大鼠。此外，胃饥饿素治疗组大鼠 PepT1 的摄取功能更好。
胃饥饿素治疗可降低脓毒症大鼠的炎症反应，并极大地上调肠道上皮细胞中 PepT1 的生理功能。
