使用动物模型对肠神经病和肠稳态对中枢神经系统变性的贡献的研究报告了不同的结果。最近,在三甲基锡处理的大鼠中观察到结肠肌间神经丛变性。该动物模型的进一步表征对于确定其研究肠神经系统与中枢神经系统变性之间关系的潜力是必要的。在这项研究中,三甲基锡处理的大鼠(8mg/kg体重,i.p.)用于测量结肠功能,结构,和可能的结肠异常。通过测量粪便颗粒输出和运输时间来评估结肠功能。进行苏木精和伊红染色和免疫组织化学以评估炎症谱和肠上皮细胞稳态。用定量PCR定量编码紧密连接蛋白的mRNA的表达以确定结肠通透性。结肠组织学检查显示粘膜免疫细胞浸润,地穴损坏,三甲基锡处理大鼠粘膜层中iNOS和精氨酸酶-1高表达。同时,三甲基锡诱导高表达iNOS,精氨酸酶-1和GFAP并增加结肠肌间神经丛的细胞死亡。在三甲基锡处理的大鼠中,低细胞增殖和低杯状细胞分布表明肠上皮细胞稳态改变。三甲基锡也上调claudin1的表达。然而,正常的结肠功能得以保留。总之,结果表明,三甲基锡诱导结肠肌间神经丛的结肠炎症和细胞死亡,破坏肠上皮细胞稳态.然而,在三甲基锡处理的大鼠中,抗炎和促炎反应之间的平衡维持正常的结肠功能.
Studies on the contribution of enteric neuropathy and intestinal homeostasis to central nervous system degeneration using animal models have reported varying results. Recently, colonic myenteric plexus degeneration was observed in
trimethyltin-treated rats. Further characterization of this animal model is necessary to determine its potential for investigating the relationship between the enteric nervous system and central nervous system degeneration. In this study,
trimethyltin-treated rats (8 mg/kg body weight, i.p.) were used to measure colonic function, structure, and possible colon abnormalities. The colonic function was assessed by measuring fecal pellet output and transit time. Hematoxylin and eosin staining and immunohistochemistry were performed to evaluate inflammatory profiles and intestinal epithelial cell homeostasis. The expression of mRNA encoding tight junction proteins was quantified with quantitative PCR to determine colon permeability. Histological examination of the colon revealed mucosal immune cell infiltration, crypt damage, and high iNOS and arginase-1 expression in the mucosal layer of trimethyltin-treated rats. At the same time,
trimethyltin induced high expression of iNOS, arginase-1, and GFAP and increased cell death in the colonic myenteric plexus. The low cell proliferation and low goblet cell distribution suggested altered intestinal epithelial cell homeostasis in trimethyltin-treated rats.
Trimethyltin also upregulated claudin 1 expression. However, normal colon function was preserved. In conclusion, the results show that
trimethyltin induces colon inflammation and cell death in the colonic myenteric plexus, and disrupts intestinal epithelial cell homeostasis. However, the balance between anti-inflammatory and pro-inflammatory responses maintains normal colon function in trimethyltin-treated rats.