Støy Ann Cathrine F, Heegaard Peter M H, Skovgaard Kerstin, Bering Stine B, Bjerre Mette, Sangild Per T
National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark.
Neonatology. 2017;111(4):289-296. doi: 10.1159/000452614. Epub 2016 Dec 24.
The risk factors for necrotizing enterocolitis (NEC) are well known, but the factors involved in the different NEC presentations remain unclear.
We hypothesized that digestive dysfunction and intestinal inflammation are mainly affected by severe NEC lesions.
In 48 preterm pigs, the association between the macroscopic NEC score (range 1-6) and the expression of 48 genes related to inflammation, morphological, and digestive parameters in the distal small intestine was investigated.
Only severe NEC cases (score of 5-6) were associated with the upregulation of genes involved in inflammation (CCL2, CCL3, CD14, CD163, CXCL8, HP, IL1B, IL1RN, IL6,IL10, NFKBIA, PTGS2 and TNFAIP3) compared to pigs that appeared healthy (score of 1-2) or showed mild NEC (score of 3-4). Pigs with a score of 5-6 had higher intestinal tissue IL-1β levels and a lower mucosal mass, villus height, and aminopeptidase N activity compared to pigs with a score of 1-4, and lower crypts and activities of lactase, dipeptidylpeptidase IV, and aminopeptidase A than pigs with a score of 1-2.
The expression of a range of inflammation-related genes was increased only in pigs with severe NEC, concomitant with morphological changes and decreased hydrolase activity. A severe inflammatory response and digestive dysfunction are associated mainly with severe NEC. Still, it remains difficult to separate the initial causes of NEC and the later intestinal consequences of NEC in both infants and experimental models.
坏死性小肠结肠炎（NEC）的危险因素已为人熟知，但不同NEC表现所涉及的因素仍不清楚。
我们推测消化功能障碍和肠道炎症主要受严重NEC病变影响。
在48头早产仔猪中，研究了宏观NEC评分（范围为1 - 6）与远端小肠中48个与炎症、形态和消化参数相关基因的表达之间的关联。
与健康仔猪（评分为1 - 2）或轻度NEC仔猪（评分为3 - 4）相比，只有严重NEC病例（评分为5 - 6）与炎症相关基因（CCL2、CCL3、CD14、CD163、CXCL8、HP、IL1B、IL1RN、IL6、IL10、NFKBIA、PTGS2和TNFAIP3）的上调有关。与评分为1 - 4的仔猪相比，评分为5 - 6的仔猪肠道组织IL - 1β水平更高，黏膜质量、绒毛高度和氨肽酶N活性更低；与评分为1 - 2的仔猪相比，其隐窝更低，乳糖酶、二肽基肽酶IV和氨肽酶A的活性更低。
一系列炎症相关基因的表达仅在严重NEC的仔猪中增加，同时伴有形态学变化和水解酶活性降低。严重的炎症反应和消化功能障碍主要与严重NEC相关。然而，在婴儿和实验模型中，仍然难以区分NEC的初始原因和NEC后期的肠道后果。
