低谷蛋白大米延缓慢性肾脏病小鼠肾功能进展的研究
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1.新沂市人民医院中医科;2.南京医科大学附属逸夫医院肾内科;3.江苏宜盛堂生命科技有限公司

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S

基金项目:

上海市“科技创新行动计划”长三角科技创新共同体领域项目(21002411500)


Study on Low Gluten Rice delaying Renal Function Progression in Mice
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SIR RUN RUN HOSPITAL NANJING MADICAL UNIVERSITY

Fund Project:

Shanghai "science and technology innovation plan " Yangtze River Delta scientific and technological Innovation Community project (No. 21002411500)

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    摘要:

    目的:评价低谷蛋白大米喂养对慢性肾脏病(Chronic Kidney Disease,CKD)小鼠的肾功能影响,为广大CKD患者日常饮食和营养干预提供新的手段和理论依据。方法:1、使用阿霉素诱导的CKD小鼠模型和糖尿病肾病小鼠模型(DKD)进行研究。每个模型小鼠都分别喂养低谷蛋白大米(LG)和正常谷蛋白大米(NG),即分组:LG-CKD vs. NG-CKD;以及LG-DKD vs. NG-DKD;2、各组小鼠连续喂养16周并定期监测食量、体重、24小时尿蛋白定量(24h UPro)以及尿微量白蛋白/尿肌酐比值(mAlb/Cr)、 空腹血糖(fasting blood glucose,FBG)、总胆固醇(total?cholesterol,TC)、甘油三酯(triglyceride,TG)以及血清尿素氮(BUN)、肌酐(sCr)以及胱抑素C ( Cys C)的变化;3、观察不同阶段肾小球病理改变和肾间质纤维化程度。结果:1、16周时,无论是CKD还是DKD 模型中,LG组和NG组小鼠的摄食量、体重变化皆无统计学意义;2、16周时,与NG-CKD相比,LG-CKD组小鼠的BUN, sCr、Cys C皆明显下降,差异有统计学意义(P值分别是0.004,0.03和0.01);8周时,尿量、尿mAlb/Cr和24h尿蛋白定量无明显差异;而在16W时,mAlb/Cr和24h尿蛋白定量明显降低,差异有统计学意义(P值分别是0.002,0.04和0.001);3、16周时,与NG-DKD组相比,LG-DKD小鼠的空腹血糖下降,差异有统计学意义,(P值 0.002);4、肾脏组织学研究提示,无论是CKD还是DKD小鼠,其LG组小鼠肾脏病理损伤程度皆较其相应的NG组小鼠轻(Masson评分对照组、CKD组、DKD组LG组分别是5.5±0.5、5.3±0.5和7.2±0.4分;NG组分别是5.4±0.5、14.2±0.7和11.8±0.6分,差异有统计学意义(P<0.05);5、小鼠肾脏转录组富集分析发现,JAK-STAT通路参与调控CKD和DKD肾损伤的发病机制;结论:低谷蛋白大米可控制DKD小鼠血糖波动、延缓CKD和DKD小鼠肾功能及肾组织纤维化进展。

    Abstract:

    Objective: To evaluate the effects of low-protein rice feeding on renal function in a chronic kidney disease (CKD) mouse model, and to provide a new dietary and nutritional intervention approach for CKD patients. Methods: 1. Doxorubicin-induced CKD and diabetic nephropathy(DKD) mouse models were studied.Mice in each model were fed either low-protein rice (LG) or normal gluten rice (NG), resulting in LG-CKD vs. NG-CKD , LG-DKD vs. NG-DKD groups. 2. The mice in each group were continuously fed for 16 weeks, and parameters including food intake, body weight , 24-hour urinary protein(24h UPro), urinary albumin-to-creatinine ratio (mAlb/Cr), fasting blood glucose (FBG), total cholesterol(TC),triglyceride(TG), blood urea nitrogen (BUN), serum creatinine (sCr), and cystatin C (Cys C) were regularly monitored.3.Renal histopathological changes and degree of renal interstitial fibrosis were examined.Results: 1)No significant differences in V and W between LG and NG groups in both CKD and DKD models. 2) At 16 weeks, BUN, sCr, and Cys C were significantly lower in LG-CKD vs. NG-CKD (p=0.004, 0.03, 0.01); mAlb/Cr and 24-hour urinary protein were significantly decreased in LG-CKD at 16 weeks (p=0.002, 0.04, 0.001). 3) Fasting blood glucose was significantly lower in LG-DKD vs. NG-DKD at 16 weeks (p=0.002). 4) Renal histological study indicated that the kidney pathological injury degree of LG group mice was less than that of NG group mice, whether CKD or DKD mice (Masson score of control group, CKD group, DKD group and LG group were 5.5±0.5, 5.3±0.5 and 7.2±0.4 points, respectively). In NG group, the results were 5.4±0.5, 14.2±0.7 and 11.8±0.6 points, respectively, with statistical significance (P < 0.05). 5) Transcriptome analysis revealed the JAK-STAT pathway was involved in regulating CKD and DKD-related kidney injury.Conclusion: Low-protein rice feeding can control blood glucose fluctuations in DKD and delay the progression of renal dysfunction and fibrosis in CKD and DKD mouse models.

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  • 收稿日期:2024-08-07
  • 最后修改日期:2024-09-23
  • 录用日期:2024-10-22
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