Yang Xiaomin, Liu Dan, Zhao Xiangzhong, Han Yafei, Zhang Xiao, Zhou Quan, Lv Qiulan
Laboratory Medicine, the Affiliated Hospital of Qingdao University, Qingdao, 266003, PR China.
Laboratory Medicine, Qingdao Fuwai Cardiovascular Hospital, PR China.
Heliyon. 2024 Aug 9;10(16):e36024. doi: 10.1016/j.heliyon.2024.e36024. eCollection 2024 Aug 30.
Hyperuricemia elevates gut permeability; however, the risk of its influence on the compromised intestinal barrier is poorly understood.
This study was carried out, aiming to elucidate the orchestrators and disruptors of intestinal barrier in hyperuricemia.
A mouse model of hyperuricemia was induced by administering adenine and oteracil potassium to mice. Allopurinol was used to decrease uric acid level, and antibiotics were administered to mice to deplete gut microbiota. Intestinal permeability was assessed using FITC-labeled dextran. Changes in gut microbial community were analyzed through 16S rRNA sequencing. IL-1β and TNF-α levels were quantified using ELISA. The expression of tight junction protein genes, , and , was determined with Q-PCR and Western blotting.
Allopurinol treatment effectively reduced intestinal permeability and serum TNF-α levels. Antibiotic treatment alleviated but not abolished intestinal permeability. Uric acid alone was insufficient to increase Coca2 monolayer permeability. Allopurinol treatment altered microbial composition and suppressed opportunistic infections. Re-establishing hyperuricemia in a germfree mouse model protected mice from intestinal injury. Allopurinol and antibiotic treatments reduced and expressions, increased and expressions but suppressed NF-ĸB p65 signaling. However, removing gut microbiota aggravated lipid metabolic dysfunction.
Gut microbiota is a direct and specific cause for intestinal barrier dysfunction.
高尿酸血症会增加肠道通透性；然而，其对受损肠屏障影响的风险尚不清楚。
开展本研究，旨在阐明高尿酸血症中肠屏障的调控因素和破坏因素。
通过给小鼠喂食腺嘌呤和氧嗪酸钾诱导高尿酸血症小鼠模型。使用别嘌呤醇降低尿酸水平，并给小鼠使用抗生素以消耗肠道微生物群。使用异硫氰酸荧光素标记的葡聚糖评估肠道通透性。通过16S rRNA测序分析肠道微生物群落的变化。使用酶联免疫吸附测定法对白细胞介素-1β和肿瘤坏死因子-α水平进行定量。用实时定量聚合酶链反应和蛋白质免疫印迹法测定紧密连接蛋白基因、、和的表达。
别嘌呤醇治疗有效降低了肠道通透性和血清肿瘤坏死因子-α水平。抗生素治疗减轻但未消除肠道通透性。单独尿酸不足以增加Caco-2单层通透性。别嘌呤醇治疗改变了微生物组成并抑制了机会性感染。在无菌小鼠模型中重建高尿酸血症可保护小鼠免受肠道损伤。别嘌呤醇和抗生素治疗降低了和的表达，增加了和的表达，但抑制了核因子-κB p65信号传导。然而，去除肠道微生物群会加重脂质代谢功能障碍。
肠道微生物群是肠屏障功能障碍的直接和特定原因。
