早期肠内营养联合益生菌对重症缺血性脑卒中患者肠道菌群及免疫功能的影响

摘要

目的 观察早期肠内营养(EN)联合益生菌对重症缺血性脑卒中患者肠道菌群及免疫功能的影响.方法 选择2017年6月至2018年6月台州市第一人民医院收治的重症缺血性脑卒中患者69例,将患者按随机数字表法分为EN联合益生菌组(35例)和单纯EN组(34例).两组均给予早期EN支持治疗,EN联合益生菌组在此基础上添加益生菌(双歧杆菌三联活菌制剂),每次0.42 g,每日3次,共14 d.观察两组患者治疗后血清炎症指标〔超敏C-反应蛋白(hs-CRP)、降钙素原(PCT)、肿瘤坏死因子-α(TNF-α)、白细胞介素-10 (IL-10)〕、肠道菌群(双歧杆菌、乳酸杆菌、产气荚膜梭菌、肠杆菌、肠球菌、拟杆菌)、肠道黏膜屏障指标〔内毒素、D-乳酸、二胺氧化酶(DAO)、肠型脂肪酸结合蛋白(I-FABP)〕及免疫指标〔免疫球蛋白(IgA、IgG、IgM)、人白细胞DR抗原(HLA-DR)〕的变化.结果 两组EN后双歧杆菌、乳酸杆菌、HLA-DR、IgA、IgG、IgM均随时间延长呈先降低后升高的趋势,于EN 3 d达到最低水平,以后逐渐升高,于EN 14 d达峰值,且EN联合益生菌组明显高于单纯EN组〔双歧杆菌(×107 cfu/g):8.31±1.49比7.49±1.32,乳酸杆菌(×107 cfu/g):8.04±1.45比 7.19±1.37,HLA-DR :(67.22±9.11)% 比(61.21±9.69)%,IgA(mg/L):170.34±40.13 比 149.54±38.76, IgG(g/L):4.88±0.88比4.31±0.86,IgM(mg/L):879.47±100.82比821.52±97.75,均P＜0.05〕.两组EN后产气荚膜梭菌、肠杆菌、肠球菌、拟杆菌、hs-CRP、PCT、TNF-α、IL-10、内毒素、D-乳酸、DAO、I-FABP随时间延长均呈先升高后降低的趋势,均于EN 3 d达到最高水平,以后逐渐降低,于EN 14 d达谷值,且EN联合益生菌组明显低于单纯EN组〔产气荚膜梭菌(×107 cfu/g):5.23±0.87比5.79±0.91,肠杆菌(×107 cfu/g):7.45±1.21比8.62±1.32,肠球菌(×107 cfu/g):7.32±1.05比8.12±1.23,拟杆菌(×107 cfu/g):9.16±1.35比9.87±1.42,hs-CRP(mg/L):18.45±12.98比25.47±15.55,PCT(ng/L):3.24±1.21比4.18±1.32,TNF-α(ng/L):9.43±8.69比13.59±9.45,IL-10(μg/L):39.45±10.72比48.52±11.42,内毒素(U/L):6.74±2.12比9.21±3.28, D-乳酸(mg/L):98.74±20.74比114.78±19.89,DAO(mg/L):21.45±8.49比29.47±9.41,I-FABP(ng/L):1.4±0.2比1.6±0.2,均P＜0.05〕.结论 早期EN联合益生菌可有效调节重症缺血性脑卒中患者肠道菌群及肠道黏膜屏障功能,降低炎症反应水平,提高机体免疫力.%Objective To explore the effects of early enteral nutrition (EN) combined with probiotics on intestinal flora and immune function in patients with severe ischemic stroke. Methods Sixty-nine severe ischemic stroke patients were admitted and continuously enrolled in Taizhou First People's Hospital from June 2017 to June 2018, and they were randomly divided into an EN combined with probiotics group (35 cases) and a simple EN group (34 cases). Early EN support was given to both groups and probiotics (Live Combined Bifidobacterium, Lactobacillus and Enterococcus capsules) was added to the EN combined with probiotics group, 0.42 g each time, 3 times a day for 14 days. The changes of serum inflammatory markers [hypersensitive C-reactive protein (hs-CRP), procalcitonin (PCT), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10)], intestinal flora (Bifidobacterium, Lactobacillus, Clostridium, Enterobacter, Enterococcus, Bacteroides), intestinal mucosal barrier [endotoxin, D-lactic acid, diamine oxidase (DAO), intestinal fatty acid binding protein (I-FABP) ], and immune indexes [immunoglobulins (IgA, IgG, IgM), human leukocyte DR antigen (HLA-DR)] were observed in two groups of patients after treatment. Results With the prolongation of time, Bifidobacteria, Lactobacilli, HLA-DR and IgA, IgG, IgM after EN in both groups all decreased first and then had a tendency of increase, all reaching the lowest value on the EN 3rd day and then gradually elevated arriving at the peak value on the EN 14th day, and the levels in EN combined with probiotics group were significantly higher than those in the simple EN group [Bifidobacterium (×107 cfu/g): 8.31±1.49 vs. 7.49±1.32, Lactobacillus (×107 cfu/g): 8.04±1.45 vs. 7.19 ±1.37, HLA-DR: (67.22±9.11)% vs. (61.21±9.69)%, IgA (mg/L): 170.34±40.13 vs. 149.54±38.76, IgG (g/L):4.88±0.88 vs. 4.31±0.86, IgM (mg/L): 879.47±100.82 vs. 821.52±97.75, all P < 0.05]. With the prolongation of time, the Clostridium, Enterobacter, Enterococcus, Bacteroides, hs-CRP, PCT, TNF-α, endotoxin, D-lactic acid, DAO, I-FABP after En in both groups all increased first and then had a tendency of decrease, reaching the highest level on the EN 3rd day, then gradually decreased arriving at the valley value on the EN 14th day, and the levels in the EN combined with probiotics group were significantly lower than those in the simple EN group [Clostridium (×107 cfu/g): 5.23±0.87 vs. 5.79±0.91, Enterobacter (×107 cfu/g): 7.45±1.21 vs. 8.62±1.32, Enterococcus (×107 cfu/g): 7.32±1.05 vs. 8.12±1.23, Bacteroides (×107 cfu/g): 9.16±1.35 vs. 9.87±1.42, hs-CRP (mg/L): 18.45±12.98 vs. 25.47±15.55, PCT (ng/L): 3.24±1.21 vs. 4.18±1.32, TNF-α (ng/L): 9.43±8.69 vs. 13.59±9.45, IL-10 (μg/L): 39.45±10.72 vs. 48.52±11.42, endotoxin (U/L): 6.74±2.12 vs. 9.21±3.28, D-lactic acid (mg/L): 98.74±20.74 vs. 114.78±19.89, DAO (mg/L): 21.45±8.49 vs. 29.47±9.41, I-FABP (ng/L): 1.4±0.2 vs. 1.5±0.2, all P < 0.05]. Conclusion Early EN combined with probiotics can effectively regulate the intestinal flora and intestinal mucosal barrier function, reduce the level of inflammatory response and enhance the body immunity in patients with severe ischemic stroke.