低谷蛋白大米延缓慢性肾脏病小鼠肾功能进展
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1.南京医科大学附属逸夫医院肾内科,江苏 南京 211166 ; 2.新沂市人民医院中医科,江苏 新沂 221400 ; 3.江苏宜盛堂生命科技有限公司,江苏 南京 210000

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S?3

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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)


Low gluten rice delayed renal function progression in mice with chronic kidney disease
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1.Department of Nephrolog,the Affiliated Sir Run Run Hospital of Nanjing Medical University,Nanjing 211166 ; 2.Department of Traditional Chinese Medicine,Xinyi People’s Hospital,Xinyi 221400 ; 3.Jiangsu Yishengtang LifeScience and Technology Co,Ltd,Nanjing 210000 ,China

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    摘要:

    目的:评价低谷蛋白(low-glutelin,LG)大米喂养对慢性肾脏病(chronic kidney disease,CKD)小鼠肾功能的影响,为 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:使用阿霉素诱导的CKD小鼠模型和高脂高糖饮食联合链脲佐菌素诱导的糖尿病肾病(diabetic kidney disease,DKD)小鼠模型,每个模型小鼠都分别喂养LG大米(含谷蛋白2.43 g/100 g、 醇溶蛋白4.47 g/100 g、总蛋白8.15 g/100 g)和正常谷蛋白(normal-glutelin,NG)大米(含谷蛋白4.85 g/100 g、醇溶蛋白1.78 g/100 g、 总蛋白7.79 g/100 g),分为LG-CKD组、NG-CKD组,以及LG-DKD组、NG-DKD组,同时给正常小鼠喂食LG大米或NG大米作为对照;各组小鼠连续喂养16周并定期监测食量、体重、24 h尿蛋白(24-hour urinary protein,24 h UPro)以及尿微量白蛋白/尿肌酐比值(urinary albumin-to-creatinine ratio,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(blood urea nitrogen,BUN)、肌酐(serum creatinine,sCr)以及胱抑素C(cystatin C,Cys C) 的变化;观察肾小球病理改变和肾间质纤维化程度。结果:喂养16周后,无论是LG-CKD组与NG-CKD组比较,还是LG-DKD 组与 NG-DKD 组比较,小鼠的摄食量、体重变化差异皆无统计学意义;喂养 16 周时,与 NG-CKD 组相比,LG-CKD 组小鼠的 BUN、sCr、Cys C水平皆明显下降,差异有统计学意义(P值分别为0.004、0.030和0.010);喂养8周时,LG-CKD组与NG-CKD组比较,尿量、尿mAlb/Cr和24 h UPro差异均无统计学意义;而在16周时,LG-CKD组mAlb/Cr和24 h UPro相比8周时明显降低(P 值分别0.040和0.001),尿量较8周时增多(P=0.043),NG-CKD组尿量较LG-CKD组明显降低(P=0.002);喂养16周时,与NG -DKD组相比,LG-DKD小鼠的FBG下降,差异有统计学意义(P=0.002);肾脏组织学研究提示,无论是CKD还是DKD小鼠,LG 喂养小鼠的肾脏病理损伤程度皆较其相应的NG喂养小鼠轻,差异有统计学意义(P < 0.05);小鼠肾脏转录组富集分析发现, JAK-STAT通路参与调控CKD肾损伤的发病机制。结论:LG大米可控制DKD小鼠血糖波动、延缓CKD和DKD小鼠的肾功能恶化及肾组织纤维化进展。

    Abstract:

    Objective:To evaluate the effects of low-glutelin(LG)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:The CKD mouse model induced by doxorubicin and diabetic nephropathy(DKD)mouse model induced by high fat and high sugar diet combined with streptozotocin were studied. Mice in each model were fed either LG rice(glutelin 2.43 g/100 g,non-absorbed albumin 4.47 g/100 g, total protein 8.15 g/100 g)or normal-glutelin(NG)rice(glutelin 4.85 g/100 g,albumin 1.78 g/100 g,total protein 7.79 g/100 g),and were divided into LG-CKD group,NG-CKD group,LG-DKD group,and NG-DKD group. Normal mice were fed with LG rice or NG rice as controls. The mice in each group were continuously fed for 16 weeks,and parameters including food intake,body weight,24-hour urinary protein(24 h 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. Renal histopathological changes and degree of renal interstitial fibrosis were examined. Results:At week 16,there was no statistically significant difference in food intake and weight changes between LG-CKD and NG-CKD groups,and between LG-DKD and NG-DKD groups. At 16 weeks,the levels of BUN,sCr,and Cys C were significantly lower in LG -CKD than in NG -CKD(P=0.004,0.030 and 0.010,respectively);the quantity of mAlb/Cr and 24 h UPro in LG-CKD group was significantly decreased(P=0.040 and 0.001, respectively),but the urine volume was significantly increased(P=0.043),compared with those indexes at 8 weeks. The urine volume in NG-CKD group was significantly decreased,compared with the LG-CKD group at 16 weeks(P=0.002). FBG was significantly lower in LG-DKD than in NG-DKD at 16 weeks(P=0.002). Renal histological study indicated that the kidney pathological injury degree of LG feeding mice was less than that of NG feeding mice,in both CKD and DKD mice,with statistical significance(P <0.05). The transcriptome analysis revealed the JAK -STAT pathway was involved in regulating CKD related kidney injury. Conclusion:LG rice feeding may control blood glucose fluctuations in DKD,delay the progression of renal dysfunction and fibrosis in CKD and DKD mouse models.

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季明,乔汉连,马梦青,陶新星,王肇炜,曹长春.低谷蛋白大米延缓慢性肾脏病小鼠肾功能进展[J].南京医科大学学报(自然科学版),2024,(11):1491-1498,1509

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  • 收稿日期:2024-08-07
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  • 在线发布日期: 2024-11-15
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