短肽型肠内营养制剂对肠黏膜炎大鼠炎症反应和免疫功能的影响

Effects of peptide-based enterai nutrition on inflammatory response and immune function in intestinal mucositis rat

目的探讨短肽型肠内营养制剂（PBEN）对肠黏膜炎大鼠机体炎症反应和免疫功能的影响。方法将48只SD雄性大鼠随机分为6组，每组8只：基础饲料组（BFG）、短肽型肠内营养制剂组（PBENG）、整蛋白型肠内营养制剂组（IPENG）、甲氨蝶呤（MTX）＋基础饲料组（MTX＋BFG）、MTX＋短肽型肠内营养制剂组（MTX＋PBENG）和MTX＋整蛋白型肠内营养制剂组（MTX＋IPENG）。在第0天和第6天，MTX＋BFG、MTX＋PBENG和MTX＋IPENG分别腹腔注射10mg／kgMTX，造成大鼠肠道持续损伤。从第1天开始，BFG和MTX＋BFG饲喂基础饲料，PBENG和MTX＋PBENG饲喂PBEN，IPENG和MTX＋IPENG饲喂整蛋白型肠内营养制剂（IPEN），每组大鼠每天按1．80kJ／g给予膳食。在第11天处死全部大鼠，HE染色观察小肠组织病理学变化，比色法测定小肠组织中髓过氧化物酶（MPO）和诱导性一氧化氮合酶（iNOS）活力以及一氧化氮（NO）含量、胸腺指数和脾腺指数，ELISA方法检测血清免疫球蛋白IgG、IgA、IgM。结果正常大鼠进食基础饲料或不同营养制剂后各指标间差异无统计学意义。MTX造模导致了大鼠肠黏膜严重损伤，MTX＋BFG各项指标与BFG之间差异有统计学意义（均P〈0．05）。给予PBEN后，MTX＋PBENG的小肠损伤评分（Chiu评分，2．3±0．69）以及小肠组织中MPO[（2．30±0．42）U／g组织]、iNOS活力[（0．37±0．06）U／mg蛋白]较MTX＋BFG大鼠[2．96±0．75、（2．98±0．23）U／g组织、（0．44±0．10）U／mg蛋白]显著降低（P=0．003，P=0．040，P=0．030）；MTX＋PBENG血清IgG[（7．45±0．67）g／L]和IgA[（0．46±0．03）g/L]均较MTX＋BFG[（6．57±0．48）g/L与（0．42±0．04）g/L]明显改善（P=0．015，P=0．021）；而NO和IgM含量差异无统计学意义（P=0．597，P=0．160）。MTX＋IPENG与MTX＋BFG各指标间差异均无统计学意义（均P〉0．05）。结论PBEN可以明显减轻肠黏膜炎大鼠的炎症反应。并提高机体免疫功能。

Objective To evaluate the effects of peptide-based enteral nutrition （PBEN） on inflammatory response and immune function in rats with intestinal mucositis. Methods 48 Sprague-Dawley male rats were randomly divided into 6 groups （all n = 8 ） ： basal feed group （BFG） , PBEN group （PBENG） , intact protein enteral nutrition group （ IPENG）, methotrexate （MTX）＋ BFG, MTX＋PBENG, and MTX＋IPENG. The rats in MTX＋BFG, MTX＋PENG, and MTX＋IPENG were intraperitoneal injected with MTX 10 mg/kg on day 0 and day 6 to induce sustained intestinal injury. From day 1, BFG and MTX＋BFG were fed with basal feed, PBENG and MTX＋PBENG with PBEN, IPENG and MTX＋IPENG with IPEN. The daily energy intake of each rat was 1.80 kJ/g body weight. All the rats were sacrificed on day 11. The pathological changes of intestinal tissue were observed with HE staining, the levels of tissue myeloperoxidase （ MPO ） , nitric oxide （NO） , inducible nitric oxide synthase （iNOS）, the thymus index and spleen gland index of intestinal tissue were measured using eolorimetry, and the serum levels of immunoglobulins IgG, IgA, and IgM were determined with enzyme-linked immunosorbent assay. Results There were no significant differences among BFG, PBENG, and IPENG in each index. Serious injury of intestinal mucosa was observed in MTX groups. Significant differences were noted in all indexes between MTX＋BFG and BFG （ all P 〈0. 05）. The mucosal damage score （Chiu score） and the level of MPO and iNOS in MTX＋PBENG were significantly lower than those in MTX＋BFG [ 2. 3 ± 0. 69 vs. 2.96 ±0.75, P=0. 003; （2.30±0.42） U/g tissue vs. （2.98 ±0.23） U/g tissue, P=0.040; （0.37 ± 0. 06） U/mg prot vs. （0.44 ±0. 10） U/rag prot, P =0. 030] ; the serum levels of IgG and IgA were significantly higher than those in MTX＋BFG （P =0. 015, P =0. 021 ） ; however, the levels of NO and IgM were not significantly different between the 2 groups （ P = 0. 597, P = 0. 160）. There were no statistically significant differences between MTX＋IPENG and MTX＋BFG in terms of the indexes （ all P 〉 0.05 ）. Conclusion PBEN can reduce the inflammation response and improve the immune function in intestinal mucositis rat.