Rivera L R, Leung C, Pustovit R V, Hunne B L, Andrikopoulos S, Herath C, Testro A, Angus P W, Furness J B
Department of Anatomy & Neuroscience, University of Melbourne, Parkville, Vic., Australia.
Neurogastroenterol Motil. 2014 Aug;26(8):1188-99. doi: 10.1111/nmo.12385. Epub 2014 Jun 23.
Disorders of gastrointestinal functions that are controlled by enteric neurons commonly accompany fatty liver disease. Established fatty liver disease is associated with diabetes, which itself induces enteric neuron damage. Here, we investigate the relationship between fatty liver disease and enteric neuropathy, in animals fed a high-fat, high-cholesterol diet in the absence of diabetes.
Mice were fed a high-fat, high-cholesterol diet (21% fat, 2% cholesterol) or normal chow for 33 weeks. Liver injury was assessed by hematoxylin and eosin, picrosirius red staining, and measurement of plasma alanine aminotransaminase (ALT). Quantitative immunohistochemistry was performed for different types of enteric neurons.
The mice developed steatosis, steatohepatitis, fibrosis, and a 10-fold increase in plasma ALT, indicative of liver disease. Oral glucose tolerance was unchanged. Loss and damage to enteric neurons occurred in the myenteric plexus of ileum, cecum, and colon. Total numbers of neurons were reduced by 15-30% and neurons expressing nitric oxide synthase were reduced by 20-40%. The RNA regulating protein, Hu, became more concentrated in the nuclei of enteric neurons after high-fat feeding, which is an indication of stress on the enteric nervous system. There was also disruption of the neuronal cytoskeletal protein, neurofilament medium.
CONCLUSIONS & INFERENCES: Enteric neuron loss and damage occurs in animals with fatty liver disease in the absence of glucose intolerance. The enteric neuron damage may contribute to the gastrointestinal complications of fatty liver disease.
由肠神经元控制的胃肠功能紊乱通常伴随脂肪肝疾病。已确诊的脂肪肝疾病与糖尿病相关，而糖尿病本身会导致肠神经元损伤。在此，我们研究在未患糖尿病的情况下，高脂、高胆固醇饮食喂养的动物中脂肪肝疾病与肠神经病变之间的关系。
将小鼠用高脂、高胆固醇饮食（21%脂肪，2%胆固醇）或正常食物喂养33周。通过苏木精和伊红染色、天狼星红苦味酸染色以及血浆丙氨酸氨基转移酶（ALT）测定来评估肝损伤。对不同类型的肠神经元进行定量免疫组化分析。
小鼠出现了脂肪变性、脂肪性肝炎、纤维化，血浆ALT升高了10倍，表明存在肝脏疾病。口服葡萄糖耐量未发生变化。在回肠、盲肠和结肠的肌间神经丛中出现了肠神经元的丢失和损伤。神经元总数减少了15% - 30%，表达一氧化氮合酶的神经元减少了20% - 40%。RNA调节蛋白Hu在高脂喂养后在肠神经元细胞核中变得更加集中，这表明肠神经系统受到了应激。神经元细胞骨架蛋白神经丝蛋白也出现了破坏。
在无葡萄糖不耐受的脂肪肝疾病动物中发生了肠神经元丢失和损伤。肠神经元损伤可能导致脂肪肝疾病的胃肠道并发症。
