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高果糖饮食改变的小肠中 ∆-9 四氢大麻酚的作用:组织病理学研究。

Effects of ∆-9 tetrahydrocannabinol on the small intestine altered by high fructose diet: A Histopathological study.

机构信息

Department of Histology and Embryology, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey.

Department of Medical Biology, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey.

出版信息

Histochem Cell Biol. 2024 Nov;162(5):363-372. doi: 10.1007/s00418-024-02311-y. Epub 2024 Aug 7.

Abstract

The consumption of fructose is increasing day by day. Understanding the impact of increasing fructose consumption on the small intestine is crucial since the small intestine processes fructose into glucose. ∆9-Tetrahydrocannabinol (THC), a key cannabinoid, interacts with CB1 and CB2 receptors in the gastrointestinal tract, potentially mitigating inflammation. Therefore, this study aimed to investigate the effects of the high-fructose diet (HFD) on the jejunum of rats and the role of THC consumption in reversing these effects. Experiments were conducted on Sprague-Dawley rats, with the experimental groups as follows: control (C), HFD, THC, and HFD + THC. The HFD group received a 10% fructose solution in drinking water for 12 weeks. THC groups were administered 1.5 mg/kg/day of THC intraperitoneally for the last four weeks. Following sacrification, the jejunum was evaluated for mucus secretion capacity. IL-6, JNK, CB2 and PCNA expressions were assessed through immunohistochemical analysis and the ultrastructural alterations via transmission electron microscopy. The results showed that fructose consumption did not cause weight gain but triggered inflammation in the jejunum, disrupted the cell proliferation balance, and increased mucus secretion in rats. Conversely, THC treatment displayed suppressed inflammation and improved cell proliferation balance caused by HFD. Ultrastructural examinations showed that the zonula occludens structures deteriorated in the HFD group, along with desmosome shrinkage. Mitochondria were found to be increased due to THC application following HFD. In conclusion, the findings of this research reveal the therapeutic potential of THC in reversing HFD-related alterations and provide valuable insights for clinical application.

摘要

果糖的消耗量日益增加。由于小肠将果糖转化为葡萄糖,因此了解不断增加的果糖消耗对小肠的影响至关重要。∆9-四氢大麻酚(THC)是一种主要的大麻素,与胃肠道中的 CB1 和 CB2 受体相互作用,可能减轻炎症。因此,本研究旨在探讨高果糖饮食(HFD)对大鼠空肠的影响,以及 THC 消耗在逆转这些影响中的作用。实验在 Sprague-Dawley 大鼠上进行,实验分组如下:对照组(C)、HFD 组、THC 组和 HFD+THC 组。HFD 组在饮用水中摄入 10%的果糖溶液,持续 12 周。THC 组在最后四周腹腔内给予 1.5mg/kg/天的 THC。处死大鼠后,评估空肠的粘液分泌能力。通过免疫组化分析评估 IL-6、JNK、CB2 和 PCNA 的表达,并通过透射电子显微镜评估超微结构改变。结果表明,果糖摄入不会导致体重增加,但会引发空肠炎症,破坏细胞增殖平衡,并增加大鼠的粘液分泌。相反,THC 治疗可抑制 HFD 引起的炎症和改善细胞增殖平衡。超微结构检查显示,HFD 组的紧密连接结构恶化,桥粒收缩。在 HFD 后应用 THC,发现线粒体增加。总之,这项研究的结果揭示了 THC 逆转 HFD 相关改变的治疗潜力,并为临床应用提供了有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/024a/11393283/0125d3b1255c/418_2024_2311_Fig1_HTML.jpg

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