Dawson P A, Huxley S, Gardiner B, Tran T, McAuley J L, Grimmond S, McGuckin M A, Markovich D
School of Biomedical Sciences, University of Queensland, St Lucia, QLD 4072, Australia.
Gut. 2009 Jul;58(7):910-9. doi: 10.1136/gut.2007.147595. Epub 2009 Feb 6.
Sulfate (SO(4)(2-)) is an abundant component of intestinal mucins and its content is decreased in certain gastrointestinal diseases, including inflammatory bowel disease. In this study, the hyposulfataemic NaS1 sulfate transporter null (Nas1(-/-)) mice were used to investigate the physiological consequences of disturbed sulfate homeostasis on (1) intestinal sulfomucin content and mRNA expression; (2) intestinal permeability and proliferation; (3) dextran sulfate sodium (DSS)-induced colitis; and (4) intestinal barrier function against the bacterial pathogen, Campylobacter jejuni.
Intestinal sulfomucins and sialomucins were detected by high iron diamine staining, permeability was assessed by fluorescein isothiocyanate (FITC)-dextran uptake, and proliferation was assessed by 5-bromodeoxyuridine (BrdU) incorporation. Nas1(-/-) and wild-type (Nas1(+/+)) mice received DSS in drinking water, and intestinal damage was assessed by histological, clinical and haematological measurements. Mice were orally inoculated with C jejuni, and intestinal and systemic infection was assessed. Ileal mRNA expression profiles of Nas1(-/-) and Nas1(+/+) mice were determined by cDNA microarrays and validated by quantitative real-time PCR.
Nas1(-/-) mice exhibited reduced intestinal sulfomucin content, enhanced intestinal permeability and DSS-induced colitis, and developed systemic infections when challenged orally with C jejuni. The transcriptional profile of 41 genes was altered in Nas1(-/-) mice, with the most upregulated gene being pancreatic lipase-related protein 2 and the most downregulated gene being carbonic anhydrase 1 (Car1).
Sulfate homeostasis is essential for maintaining a normal intestinal metabolic state, and hyposulfataemia leads to reduced intestinal sulfomucin content, enhanced susceptibility to toxin-induced colitis and impaired intestinal barrier to bacterial infection.
硫酸盐（SO₄²⁻）是肠道黏蛋白的丰富成分，在包括炎症性肠病在内的某些胃肠道疾病中其含量会降低。在本研究中，使用低硫酸盐血症的NaS1硫酸盐转运蛋白缺失（Nas1⁻/⁻）小鼠来研究硫酸盐稳态紊乱对以下方面的生理影响：（1）肠道硫黏蛋白含量和mRNA表达；（2）肠道通透性和增殖；（3）硫酸葡聚糖钠（DSS）诱导的结肠炎；以及（4）肠道对细菌病原体空肠弯曲菌的屏障功能。
通过高铁二胺染色检测肠道硫黏蛋白和涎黏蛋白，通过异硫氰酸荧光素（FITC）-葡聚糖摄取评估通透性，通过5-溴脱氧尿苷（BrdU）掺入评估增殖。Nas1⁻/⁻和野生型（Nas1⁺/⁺）小鼠饮用含DSS的水，通过组织学、临床和血液学测量评估肠道损伤。小鼠经口接种空肠弯曲菌，评估肠道和全身感染情况。通过cDNA微阵列确定Nas1⁻/⁻和Nas1⁺/⁺小鼠回肠的mRNA表达谱，并通过定量实时PCR进行验证。
Nas1⁻/⁻小鼠表现出肠道硫黏蛋白含量降低、肠道通透性增强以及DSS诱导的结肠炎，经口用空肠弯曲菌攻击时会发生全身感染。Nas1⁻/⁻小鼠中41个基因的转录谱发生改变，上调最明显的基因是胰腺脂肪酶相关蛋白2，下调最明显的基因是碳酸酐酶1（Car1）。
硫酸盐稳态对于维持正常的肠道代谢状态至关重要，低硫酸盐血症会导致肠道硫黏蛋白含量降低、对毒素诱导的结肠炎易感性增加以及肠道对细菌感染的屏障功能受损。
