摘要
背景:枸杞多糖作为一种天然活性成分,具有降低血糖以及改善糖尿病相关症状的潜力。然而,从肠道菌群的角度,枸杞多糖对糖脂异常影响的潜在因素尚未完全阐明。目的:探究枸杞多糖在2型糖尿病中的作用及相关机制。方法:从18只8周龄雄性SD大鼠中随机选取6只为空白对照组,其余12只大鼠给予高糖高脂饲料饲养8周+尾静脉单次注射1%链脲佐菌素溶液构建2型糖尿病模型,造模成功后随机分为模型对照组(n=6)和枸杞多糖组(n=6)。枸杞多糖组大鼠按照200 mg/(kg·d)的剂量灌胃枸杞多糖溶液,2 mL/次,1次/d,连续灌胃12周,收集大鼠血清及粪便。通过16S rDNA测序分析肠道菌群,采用α多样性、β多样性及主成分分析等方法表征菌群丰度与结构特征;采用液相色谱-质谱联用法检测短链脂肪酸水平;通过ELISA法检测糖脂代谢、胰岛素抵抗及炎症反应相关指标。结果与结论:①与模型对照组相比,枸杞多糖组高密度脂蛋白胆固醇水平升高,总胆固醇、三酰甘油和低密度脂蛋白胆固醇水平降低,说明枸杞多糖改善了2型糖尿病大鼠的脂质积累,并抑制体质量减轻;②与模型对照组相比,枸杞多糖组白细胞介素6、肿瘤坏死因子α以及血糖水平降低,胰岛素以及胰高血糖素样肽1水平升高,说明枸杞多糖有效抑制了炎症反应和胰岛素抵抗;③枸杞多糖显著改善了肠道菌群的组成,增加了Lachnospiraceae_NK4A136_group、Clostridia_UCG-014_unclassified、Monoglobus、Phascolarctobacterium、Candidatus_Saccharimonas、Desulfovibrionaceae unclassified以及Desulfovibrio丰度,减少了Muribaculaceae_unclassified和Enterorhabdus丰度;④枸杞多糖还显著提高了短链脂肪酸水平,并且Clostridia_UCG-014_unclassified、Candidatus_Saccharimonas和Muribaculaceae_unclassified可能参与调节丁酸的生成,以改善2型糖尿病大鼠的糖脂代谢,Lachnospiraceae_NK4A136_group、Monoglobus和Desulfovibrionaceae unclassified可能参与调节异丁酸的生成,以抑制胰岛素抵抗以及改善脂代谢;⑤枸杞多糖可通过增加Firmicutes_unclassified、Clostridia_UCG-014_unclassified、Intestinimona和Colidextribacter以及抑制Kineothrix的丰度来改善2型糖尿病大鼠的炎症反应。
BACKGROUND:Lycium barbarum polysaccharide is a natural active ingredient with potential to lower blood glucose and improve diabetes-related symptoms.However,from the perspective of gut microbiota,the underlying factors for the effects of Lycium barbarum polysaccharide on glycolipid abnormalities have not been fully elucidated.OBJECTIVE:To investigate the effect of Lycium barbarum polysaccharide on type 2 diabetes mellitus and its related mechanism.METHODS:Six male Sprague-Dawley rats aged 8 weeks were randomly selected from 18 rats to form a blank control group.The remaining 12 rats were fed a high-sugar,high-fat diet for 8 weeks and then received a single tail vein injection of 1%streptozotocin to establish a type 2 diabetes model.After successful modeling,the rat models were then randomly divided into a model control group(n=6)and a Lycium barbarum polysaccharide group(n=6).Rats in the Lycium barbarum polysaccharide group were administered Lycium barbarum polysaccharide solution via gavage at a dose of 200 mg/(kg·d),2 mL per dose,once daily,for 12 consecutive weeks.After the intervention,rat serum and feces were collected.16S rDNA sequencing was used to analyze the gut microbiota,andαdiversity,βdiversity and principal component analysis were used to characterize the abundance and structural characteristics of the microbiota.Liquid chromatography-mass spectrometry was used to detect the level of short-chain fatty acids.The indicators of glucose and lipid metabolism,insulin resistance and inflammatory response were detected by ELISA.RESULTS AND CONCLUSION:(1)Compared with the model control group,Lycium barbarum polysaccharide could increase the level of high-density lipoprotein cholesterol,reduce the levels of total cholesterol,triglyceride and low-density lipoprotein cholesterol,indicating Lycium barbarum polysaccharide improves lipid accumulation and inhibits body mass loss in type 2 diabetic rats.(2)Compared with the model control group,Lycium barbarum polysaccharide reduced the levels of interleukin-6,tumor necrosis factor-αand blood glucose,and increased the levels of insulin and glucagon-like peptide-1,indicating that Lycium barbarum polysaccharide effectively inhibits inflammation and insulin resistance.(3)Lycium barbarum polysaccharide significantly improved the composition of gut microbiota,increased the abundance of Lachnospiraceae_NK4A136_group,Clostridia_UCG-014_unclassified,Monoglobus,Phascolarctobacterium,Candidatus_Saccharimon,Desulfovibrionaceae unclassified,and Desulfovibrio,decreased the abundance of Muribaculaceae_unclassified and Enterorhabdus.(4)Lycium barbarum polysaccharide also significantly increased the level of short-chain fatty acids.Clostridia_UCG-014_unclassified,Candidatus_Saccharimonas and Muribaculaceae_unclassified may be involved in regulating the production of butyrate,thereby improving glucose and lipid metabolism in type 2 diabetic rats,whereas Lachnospiraceae_NK4A136_group,Monoglobus and Desulfovibrionaceae unclassified may be involved in regulating the production of isobutyl acid to inhibit insulin resistance and improve lipid metabolism.(5)Lycium barbarum polysaccharide can improve inflammation in type 2 diabetic rats by increasing the abundance of Firmicutes_unclassified,Clostridia_UCG-014_unclassified,Intestinimona and Colidextribacter,and inhibiting the abundance of Kineothrix.
作者
王京峰
冯硕
曹炫
李晓琳
Wang Jingfeng;Feng Shuo;Cao Xuan;Li Xiaolin(Harbin Sport University,Harbin 150008,Heilongjiang Province,China)
出处
《中国组织工程研究》
2026年第29期7592-7602,共11页
Chinese Journal of Tissue Engineering Research
基金
黑龙江省自然科学基金项目(LH2024G003),项目负责人:李晓琳
哈尔滨体育学院实验室平台专项(LAB2021-06),项目负责人:李晓琳。
关键词
枸杞多糖
肠道菌群
2型糖尿病
短链脂肪酸
糖脂代谢
炎症
Lycium barbarum polysaccharide
gut microbiota
type 2 diabetes mellitus
short-chain fatty acids
glucose and lipid metabolism
inflammation
