目的 针对慢性肾病患者（chronic kidney disease, CKD）,基于肠-肾轴理论,设计一款添加益生菌（干酪乳杆菌）的全营养配方食品,并通过动物模型验证其效果。方法 设计基础配方组（basic formula group, BFG）及含1×10⁸CFU/100 g干酪乳杆菌的益生菌配方组（probiotics containing formula group, PFG）;50只SPF级雄性SD大鼠,10只作为空白对照组（blank control group, BCG）组,其余40只经250 mg/(kg・d)腺嘌呤混悬液灌胃6 w构建CKD模型,将30只造模成功大鼠随机分为3组,分别为CKD组、BFG组、PFG组（各10只）,BCG组、CKD组给予普通饲料,BFG组、PFG组分别给予对应配方饲料,共干预5 w。每天记录进食量,每周检测体重;实验结束后,收集大鼠24h尿液检测24小时尿蛋（24h-UTP）,麻醉大鼠,腹主动脉取血检测肾功能指标（Scr、BUN）、摘取肾脏称重,比较各组之间肾脏系数;HE及Masson染色进行肾脏病理观察;取大鼠粪便进行肠道菌群（16SrRNA高通量测序）检测。结果 与 BCG 组相比,腺嘌呤灌胃造模后大鼠Scr、BUN水平均显著升高（P<0.001）,提示 CKD 大鼠模型构建成功;与CKD组相比,BFG组、PFG组大鼠体重显著上升（P<0.05）,Scr、BUN显著降低（P<0.05）,肾组织病理损伤减轻,PFG组肾脏系数改善更优（P<0.05）,CKD组肠道菌群Chao1指数显著升高（P<0.05）,PFG组双歧杆菌属等有益菌丰度增加（P<0.05）;各组大鼠摄食量无统计学差异（P >0.05）。结论 所设计的全营养基础配方食品可改善CKD大鼠肾功能,而添加干酪乳杆菌可通过调节肠道菌群进一步改善CKD大鼠肾功能,为CKD患者专用特医食品开发提供了实验依据。
Abstract
Objective Based on the gut-kidney axis theory, to design a complete nutritional formula supplemented with Lactobacillus casei for patients with chronic kidney disease (CKD) and verify its renoprotective efficacy in an animal model. Methods A basic formula group (BFG) and a probiotic formula group (PFG) containing 1×108 CFU/100 g Lactobacillus casei were formulated. Fifty SPF-grade male SD rats were used: 10 served as the blank control group (BCG), and the remaining 40 received adenine suspension via gavage at 250 mg/(kg·d) for 6 weeks to induce CKD. Thirty successfully modeled rats were randomly assigned to the CKD, BFG, and PFG groups (n=10 each). The BCG and CKD groups were fed standard chow, while the BFG and PFG groups received their respective formula diets for 5 weeks. Food intake was recorded daily and body weight weekly. At the end of intervention, 24-hour urine was collected for 24-hour urinary total protein (24h-UTP) measurement; blood was drawn from the abdominal aorta for serum creatinine (Scr) and blood urea nitrogen (BUN) assays; kidneys were harvested and weighed to calculate the kidney-to-body weight ratio. Renal histopathology was evaluated by HE and Masson staining, and fecal gut microbiota was analyzed by 16S rRNA high-throughput sequencing. Results Compared with the BCG group, adenine-treated rats showed markedly elevated Scr and BUN (both P < 0.001), confirming successful CKD modeling. Compared with the CKD group, both the BFG and PFG groups exhibited significantly increased body weight (P < 0.05), reduced Scr and BUN (P < 0.05), and attenuated renal pathological damage; the PFG group showed superior improvement in the kidney-to-body weight ratio (P < 0.05). The Chao1 index of gut microbiota was significantly higher in the CKD group (P < 0.05), and the abundance of beneficial bacteria such as Bifidobacterium was increased in the PFG group (P < 0.05). No significant difference in food intake was observed among groups (P>0.05). Conclusion The complete nutritional basic formula improves renal function in CKD rats, and Lactobacillus casei supplementation further enhances this benefit by modulating gut microbiota, providing experimental support for the development of specialized medical foods for CKD patients.
关键词
肠-肾轴 /
慢性肾病 /
全营养配方食品 /
益生菌 /
肠道菌群
Key words
gut-kidney axis /
chronic kidney disease /
total nutrition formula food /
probiotics /
gut microbiota
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基金
黑龙江省自然科学基金（No. LH2022H050）
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