The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou Province, People's Republic of China.
The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou Province, People's Republic of China.
J Pharmacol Sci. 2020 Jun;143(2):89-96. doi: 10.1016/j.jphs.2020.02.009. Epub 2020 Feb 28.
Tong-fu-li-fei (TFL) prescription has already used to treat sepsis in clinic but its mechanism remains unclear. Here, we aimed to investigate the effect and mechanism of Tong-fu-li-fei (TFL) prescription on sepsis in rats. The Sprague-Dawley rats were divided into the sham group, model group, the TFL 3.6 g/kg and 7.2 g/kg-treated group. The sepsis model was induced by cecal ligation and puncture (CLP). After 7 days, TFL treatment improved the survival rate of CLP rats and alleviated sepsis-induced intestinal mucosal injury. The ELISA assay showed that inflammatory cytokine expressions including TNF-α and IL-1β in serum from TFL-treated rats were lower than that in the model. And TNF-α, IL-1β and IL-6 from intestinal tissues were also decreased and IL-10 was increased in TFL-treated rats. Meanwhile the expression levels of the tight junction molecules occludin, claudin-1, and zonula occludens-1 (ZO-1) mRNA and protein expressions examined by RT-PCR, western blot and immunohistochemistry, were also restored in rats that received TFL treatment. Our data showed that TFL mitigates the inflammatory response and maintains intestinal barrier function in sepsis through upregulating ZO-1/occludin/claudin-1 expression, providing a good experimental basis for its clinical treatment of sepsis.
通腑利水方已用于临床治疗脓毒症，但作用机制尚不清楚。本研究旨在探讨通腑利水方对脓毒症大鼠的作用及机制。将 Sprague-Dawley 大鼠分为假手术组、模型组、通腑利水方 3.6 g/kg 和 7.2 g/kg 治疗组。采用盲肠结扎穿孔（CLP）法建立脓毒症模型。7 天后，通腑利水方治疗可提高 CLP 大鼠的存活率，并减轻脓毒症引起的肠道黏膜损伤。ELISA 检测结果显示，与模型组相比，通腑利水方治疗组大鼠血清中 TNF-α 和 IL-1β 等炎症细胞因子的表达水平降低。通腑利水方治疗组大鼠的肠道组织中 TNF-α、IL-1β 和 IL-6 降低，IL-10 升高。此外，RT-PCR、western blot 和免疫组化检测结果显示，通腑利水方治疗可恢复大鼠肠道组织中紧密连接分子 occludin、claudin-1 和 zonula occludens-1（ZO-1）的 mRNA 和蛋白表达水平。以上结果表明，通腑利水方通过上调 ZO-1/occludin/claudin-1 的表达，减轻脓毒症大鼠的炎症反应，维持肠道屏障功能，为其临床治疗脓毒症提供了良好的实验依据。
