益生菌对重型颅脑损伤患者血清胃饥饿素水平的影响

Effects of probiotics on serum levels of Ghrelin in patients with severe craniocerebral trauma

目的探讨益生菌对重型颅脑损伤患者血清胃饥饿素(Ghrelin)水平的影响。方法采用前瞻性随机对照研究方法,选择川北医学院附属医院2018年2月至2019年1月收治的重型颅脑损伤患者52例作为研究对象,将患者按随机数字表法分为益生菌组和对照组,每组26例,剔除3例生存时间<5 d的患者,最终益生菌组纳入24例,对照组纳入25例。所有患者均按照《颅脑创伤临床救治指南》给予常规治疗,并于入院后24~48 h内开始经鼻胃管给予肠内营养(EN);益生菌组在此基础上给予益生菌制剂,每次3.5 g、每日3次,共用21 d。于EN 1、4、8、15 d取患者空腹静脉血,分离血清,采用酶联免疫吸附试验(ELISA)检测血清Ghrelin及酰基化Ghrelin水平;比较两组患者EN不耐受症状和达目标EN量所需时间。结果对照组和益生菌组患者干预前Ghrelin及酰基化Ghrelin水平比较差异均无统计学意义〔Ghrelin(ng/L):28.6±13.4比27.9±14.8,酰基化Ghrelin(ng/L):12.4±5.9比11.8±6.1,均P>0.05〕。随时间延长,两组Ghrelin及酰基化Ghrelin水平均逐渐升高,EN 4 d益生菌组Ghrelin水平均较对照组稍低(ng/L:36.1±8.5比40.1±15.5),酰基化Ghrelin较对照组稍高(ng/L:19.3±5.9比15.5±9.0),两组比较差异均无统计学意义(均P>0.05);但益生菌组Ghrelin的升高程度较对照组缓慢,EN 8 d和15 d益生菌组Ghrelin水平均显著低于对照组(ng/L:8 d为42.6±9.4比60.8±12.3,15 d为43.7±8.0比66.7±21.4,均P<0.05);益生菌组酰基化Ghrelin的升高程度较对照组明显,EN 8 d和15 d益生菌组酰基化Ghrelin水平显著高于对照组(ng/L:8 d为28.1±5.3比22.6±10.8,15 d为30.3±4.4比25.4±10.5,均P<0.05)。益生菌组发生EN不耐受症状的患者比例较对照组显著减少〔4.17%(1/24)比48.00%(12/25),χ^2=12.070,P=0.001〕;益生菌组达目标EN量所需时间也显著早于对照组(d:3.79±0.59比6.04±3.85,Z=-2.362,P=0.018)。结论益生菌可改善重型颅脑损伤患者对EN的耐受性,其内在机制可能与酰基化Gghrelin水平增高有关。

Objective To investigate the effects of probiotics on serum levels of Ghrelin in patients with severe craniocerebral trauma.Methods A prospective randomized controlled study was conducted.The 52 severe craniocerebral trauma patients were selected as research objects and divided into probiotics and control group(each group with 26 cases)by random number table method.Three patients with survival time<5 days were excluded,and at last 24 cases in probiotics group and 25 cases in control group were included.All patients received conventional treatment according to the Guidelines for the Clinical Management of Traumatic Brain Injury and enteral nutrition(EN)within 24-48 hours after admission through nasogastric tube.In addition,the probiotics group received viable probiotics(3.5 g/time,for 3 times per day)for 21 days.The fasting venous blood samples were collected to determine the serum levels of Ghrelin and acyl Ghrelin by enzyme linked immunoadsordent assay(ELISA)on days 1,4,8,and 15 after intervention.EN intolerance and the time to targeted EN goals of two groups were compared.Results There were no significant differences in terms of the serum Ghrelin and acyl Ghrelin levels between two groups before intervention[Ghrelin(ng/L):28.6±13.4 vs.27.9±14.8,acyl Ghrelin(ng/L):12.4±5.9 vs.11.8±6.1,both P>0.05].Over time,the levels of Ghrelin and acyl Ghrelin increased and compared with the control group on day 4,the probiotics group showed lower levels of Ghrelin(ng/L:36.1±8.5 vs.40.1±15.5)and higher levels of acyl Ghrelin(ng/L:19.3±5.9 vs.15.5±9.0),without significant differences(both P>0.05).The increase of Ghreliln in probiotics group was slower than that in control group.On days 8 and 15 after EN intervention,significantly lower serum level of Ghrelin(ng/L:8 days was 42.6±9.4 vs.60.8±12.3,15 days was 43.7±8.0 vs.66.7±21.4,both P<0.05),and higher serum level of acyl Ghrelin were observed in the probiotics group compared with those of the control group(ng/L:8 days was 28.1±5.3 vs.22.6±10.8,15 days was 30.3±4.4 vs.25.4±10.5,P<0.05).The increase of Ghrelin in probiotics group was more obvious than that of control group.The probiotics group exhibited significantly less patients with EN intolerance[4.17%(1/24)vs.48.00%(12/25),χ^2=12.070,P=0.001]and shorter days to targeted EN goals than that in the control group(days:3.79±0.59 vs.6.04±3.85,Z=-2.362,P=0.018).Conclusion Probiotics could improve EN tolerance in patients with severe craniocerebral trauma.The underlying mechanisms may be related to the increase of serum levels of acyl Ghrelin.