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一种中药配方(CoTOL)对接种肠道细菌的肥胖高尿酸血症小鼠血清尿酸和肠道菌群的影响

Effect of a Traditional Chinese Medicine Formula (CoTOL) on Serum Uric Acid and Intestinal Flora in Obese Hyperuricemic Mice Inoculated with Intestinal Bacteria.

作者信息

Gao Yan, Sun Jing, Zhang Yi, Shao Tiejuan, Li Haichang, Wang Meijiao, Zhang Li, Bian Hua, Wen Chengping, Xie Zhijun, Lv Huiqing

机构信息

Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

出版信息

Evid Based Complement Alternat Med. 2020 Dec 23;2020:8831937. doi: 10.1155/2020/8831937. eCollection 2020.

Abstract

CoTOL is a traditional Chinese medicine (TCM) formula in clinics for treating gout and hyperuricemia, especially in obese patients with recurrent attacks. However, fewer studies have investigated how CoTOL impacts the intestinal flora in reducing uric acid. In the present, we analyze the bacteria targeted by ingredients of CoTOL and evaluate the effects of CoTOL on uric acid and intestinal flora in a mice model of obese hyperuricemia inoculated with xanthine dehydrogenase- (XOD-) producing bacteria, . Firstly, ingredients of herbs in CoTOL and gene target by these ingredients were retrieved from TCMID 2.0, and these genes were screened by DAVID Bioinformatics Resources 6.8, deciphered to retrieve the bacteria. Then, 3-4-week-old male C57bl/6j mice were randomly divided into 6 groups and fed with high fat diet for 8 weeks up to obesity standard. The mice were inoculated intragastrically with 5 × 10 CFU 3 times at the 5, 6, and 7 week and intragastrically administrated with uricase inhibitor, potassium-oxonate (PO, 250 mg/kg), to induce hyperuricemia at the 8 week, once a day for 7 consecutive days, respectively (IB model). IB model plus CoTOL (0.4 ml/20g) and allopurinol (40 mg/kg) were administrated by gavage at the 5 week, once a day for 4 weeks. The feces and blood in each group were sampled at the 4 and 8 week. With no bacteria inoculation, CoTOL, allopurinol, and blank group were treated with CoTOL and allopurinol or water, respectively. 44 species of bacteria (i.e., etc.) genes were targeted by 6 ingredients of 6 herbs in CoTOL. Inoculation with significantly caused the elevation of uric acid and the change of intestinal flora structure, whereas treatment with CoTOL significantly increased the abundance of and those of and decreased. Furthermore, CoTOL exhibited a unique effect on reducing weight unobserved in allopurinol intervention. The present study, for the first time, demonstrated that CoTOL has beneficial effects on hyperuricemia and overweight, which may be attributed to regulating material metabolism and improving the structure or function of intestinal flora. Thus, CoTOL may be a promising therapy for hyperuricemia and overweight in chronic gout management and can be integrated with conventional treatments.

摘要

痛风定(CoTOL)是临床用于治疗痛风和高尿酸血症的中药方剂,尤其适用于肥胖且痛风反复发作的患者。然而,关于痛风定在降低尿酸过程中如何影响肠道菌群的研究较少。在本研究中,我们分析了痛风定成分所靶向的细菌,并在接种产黄嘌呤脱氢酶(XOD)细菌的肥胖高尿酸血症小鼠模型中评估了痛风定对尿酸和肠道菌群的影响。首先,从中药整合药理学平台(TCMID)2.0中检索痛风定中草本植物的成分及其基因靶点,然后通过DAVID生物信息学资源6.8对这些基因进行筛选,解码以检索相关细菌。将3 - 4周龄的雄性C57bl/6j小鼠随机分为6组,给予高脂饮食8周直至达到肥胖标准。在第5、6、7周,小鼠经胃内接种5×10⁸CFU细菌3次,并在第8周经胃内给予尿酸酶抑制剂氧嗪酸钾(PO,250mg/kg),连续7天,每天1次,以诱导高尿酸血症(IB模型)。在第5周,对IB模型小鼠加用痛风定(0.4ml/20g)和别嘌醇(40mg/kg)进行灌胃给药,每天1次,持续4周。在第4周和第8周采集每组小鼠的粪便和血液样本。对于未接种细菌的痛风定组、别嘌醇组和空白组,分别给予痛风定、别嘌醇或水进行处理。痛风定中6味中药的6种成分靶向44种细菌(如……等)的基因。接种细菌显著导致尿酸升高和肠道菌群结构改变,而痛风定治疗显著增加了……的丰度,……和……的丰度降低。此外,痛风定在减轻体重方面表现出独特的作用,这在别嘌醇干预中未观察到。本研究首次证明痛风定对高尿酸血症和超重具有有益作用,这可能归因于其调节物质代谢以及改善肠道菌群的结构或功能。因此,痛风定可能是慢性痛风管理中治疗高尿酸血症和超重的一种有前景的疗法,并且可以与传统治疗方法相结合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07a8/7775141/cac76232ba8c/ECAM2020-8831937.001.jpg

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