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姜黄素对大鼠肠道炎症相关运动障碍的保护作用。

Protective effects of curcumin against rat intestinal inflammation‑related motility disorders.

机构信息

Department of Basic Medicine, Chongqing Three Gorges Medical College, Chongqing 404120, P.R. China.

出版信息

Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.12030. Epub 2021 Mar 24.

Abstract

Intestinal inflammation frequently occurs alongside dysmotility, which is characterized by altered myosin light chain phosphorylation levels. Curcumin, an active component from the ginger family, is reported to confer anti‑inflammatory effects. However, the effects of curcumin on both diarrhea and constipation associated inflammation remains to be elucidated. The present study was designed to investigate the effects of curcumin on diarrhea and constipation and to determine the related mechanisms. Sprague‑Dawley rats were used to establish diarrhea and constipation models via intracolonic acetic acid (4%) instillation or cold water gavage for 2 weeks, respectively. Blood samples were collected to measure the serum levels of the cytokines TNF‑α and IL‑1β using ELISA kits. Western blotting was performed to measure NF‑κB, RhoA, Rho‑related kinase 2, phosphorylated MLC, phosphorylated myosin phosphorylated target subunit 1, 130k Da‑MLC kinase (MLCK), c‑kit tyrosine kinase protein expression, and reverse transcription‑quantitative PCR was conducted to measure MLCK expression levels. The results indicated that curcumin reversed the elevations in the pro‑inflammatory cytokines IL‑1β and TNF‑α by inhibiting the NF‑κB pathway in rats with diarrhea and constipation. The results also indicated that myosin light chain (MLC) phosphorylation in intestinal smooth muscle was positively and negatively associated with the motility of inflammation‑related diarrhea and constipation in rats, respectively. Curcumin significantly reversed the increased MLC phosphorylation in the jejunum of the rats with diarrhea, significantly enhanced the reductions in inflammatory mediators, including TNF‑α and IL‑1β, of rats with constipation and significantly ameliorated the related hyper‑motility and hypo‑motility in rats with both diarrhea and constipation. In conclusion, the potential roles of the MLC kinase, c‑kit tyrosine and Rho A/Rho‑associated kinase 2 pathways, which are involved in curcumin‑induced amelioration of inflammation‑related diarrhea and constipation, were explored in the present study. Results from the present study suggested that curcumin has potential therapeutic value for treating intestinal inflammation and inflammation‑related motility disorders.

摘要

肠道炎症常伴有运动障碍,其特征为肌球蛋白轻链磷酸化水平改变。姜黄素是姜科的一种活性成分,据报道具有抗炎作用。然而,姜黄素对腹泻和便秘相关炎症的影响仍有待阐明。本研究旨在探讨姜黄素对腹泻和便秘的影响,并确定相关机制。使用 Sprague-Dawley 大鼠通过直肠内乙酸(4%)灌注或冷水灌胃分别建立腹泻和便秘模型 2 周。收集血液样本,通过 ELISA 试剂盒测量血清中细胞因子 TNF-α和 IL-1β的水平。通过 Western blot 测定 NF-κB、RhoA、Rho 相关激酶 2、磷酸化肌球蛋白轻链、磷酸化肌球蛋白磷酸化靶亚单位 1、130kDa-MLC 激酶(MLCK)、c-kit 酪氨酸激酶蛋白表达,通过逆转录-定量 PCR 测定 MLCK 表达水平。结果表明,姜黄素通过抑制腹泻和便秘大鼠的 NF-κB 通路,逆转促炎细胞因子 IL-1β和 TNF-α的升高。结果还表明,肠平滑肌肌球蛋白轻链(MLC)磷酸化与大鼠炎症相关腹泻和便秘的运动性呈正相关和负相关。姜黄素显著逆转了腹泻大鼠空肠 MLC 磷酸化的增加,显著增强了便秘大鼠炎症介质 TNF-α和 IL-1β的减少,并显著改善了腹泻和便秘大鼠的相关高动力和低动力。总之,本研究探讨了参与姜黄素诱导的炎症相关腹泻和便秘改善的 MLC 激酶、c-kit 酪氨酸和 Rho A/Rho 相关激酶 2 通路的潜在作用。本研究结果表明,姜黄素具有治疗肠道炎症和炎症相关运动障碍的潜在治疗价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22a2/8008224/efee97bd48a5/mmr-23-05-12030-g00.jpg

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