Nicotinamide Riboside Improves Enteric Neuropathy in Streptozocin-Induced Diabetic Rats Through Myenteric Plexus Neuroprotection.
Nicotinamide Riboside Improves Enteric Neuropathy in Streptozocin-Induced Diabetic Rats Through Myenteric Plexus Neuroprotection.
复制标题
烟酰胺核苷通过肌间丛神经保护改善链佐星诱导的糖尿病大鼠的肠神经病变。
DOI：
10.1007/s10620-023-07913-5
复制
发表时间：
2023
影响因子：
3.1
通讯作者：
Willis,DiannaE
中科院分区：
文献类型：
--
作者：
Costa,ChristopherJ;Cohen,MelanieW;Goldberg,DavidC;Mellado,Wilfredo;Willis,DiannaE
背景：糖尿病引起全身氧化应激，部分原因是高血糖和活性氧的产生。高达75%的糖尿病患者表现为影响肠神经系统的自主神经病变。人类的缺陷是慢性运动障碍，要么增加（如便秘），要么减少（如腹泻）胃肠道总传递时间。这些都是在链脲佐菌素诱导的糖尿病大鼠中重现的，这是一种I型糖尿病模型。目的探讨烟酰胺腺苷二核苷酸（NAD）前体烟酰胺核苷（NR）对诱导糖尿病大鼠运动障碍的影响，以及粪便微生物群移植（FMT）是否能产生相同的结果。材料与方法采用为期6周的治疗模式，每48 h腹腔注射NR。采用胭脂红法每周评估总胃肠道传递时间。高血糖诱导后3周，在nr治疗动物和未治疗动物之间进行FMT。显著结果NR的使用改善了糖尿病大鼠的总胃肠道传递时间。16S微生物组测序显示，在接受FMT的动物中，α和β多样性下降，但没有变化。糖尿病动物经NR治疗后，小肠和大肠肌丛神经节密度均有改善。结论snr治疗可改善诱导糖尿病动物的胃肠总传递时间。这与诱导糖尿病大鼠小肠和大肠肌丛的神经保护作用有关。这是显示NR作为糖尿病肠神经病变治疗的益处的重要的第一步。图片摘要：链脲菌素诱导的糖尿病大鼠腹腔注射烟酰胺核苷后，转运时间缩短，肌丛神经节密度增加。
BackgroundDiabetes Mellitus causes a systemic oxidative stress due in part to the hyperglycemia and the reactive oxygen species generated. Up to 75% of diabetic patients present with an autonomic neuropathy affecting the Enteric Nervous System. Deficits in the human population are chronic dysmotilities with either increased (i.e.,constipation) or decreased (i.e.,diarrhea) total gastrointestinal transit times. These are recapitulated in the streptozocin-induced diabetic rat, which is a model of Type I Diabetes Mellitus.AimsExamine the effects that a precursor of nicotinamide adenosine dinucleotide (NAD), nicotinamide riboside (NR), had on the development of dysmotility in induced diabetic rats and if fecal microbiota transplant (FMT) could produce the same results.Materials and MethodsUtilizing a 6-week treatment paradigm, NR was administered intraperitoneally every 48 h. Total gastrointestinal transit time was assessed weekly utilizing the carmine red method. Three weeks following hyperglycemic induction, FMT was performed between NR-treated animals and untreated animals.Significant ResultsThere is improvement in overall gastrointestinal transit time with the use of NR. 16S microbiome sequencing demonstrated decreased alpha and beta diversity in induced diabetic rats without change in animals receiving FMT. Improvements in myenteric plexus ganglia density in small and large intestines in diabetic animals treated with NR were seen.ConclusionsNR treatment led to functional improvement in total gastrointestinal transit time in induced diabetic animals. This was associated with neuroprotection in the myenteric plexuses of both small and large intestines of induced diabetic rats. This represents an important first step in showing NR’s benefit as a treatment for diabetic enteric neuropathy.Graphical AbstractStreptozocin-induced diabetic rats have improved transit times and increased myenteric plexus ganglia density when treated with intraperitoneal nicotinamide riboside.