摘要
目的探究阿尔茨海默病(Alzheimer's disease,AD)患者肠道炎症相关指标变化及其与疾病严重程度相关性。方法纳入2021年8月至2023年3月郑州人民医院收治的52例AD患者及60例健康对照者进行前瞻性研究,使用ELISA法检测AD患者及对照者入院时粪便中粪钙卫蛋白(fecal calprotectin,FC)、粪α-1-抗胰蛋白酶(fecalα-1-antitrypsin,FAT)、血中脂多糖(lipopolysaccharide,LPS)、脂多糖结合蛋白(lipopolysaccharide binding protein,LBP)水平,比较两组上述指标差异;收集AD患者入院时蒙特利尔认知评估量表(montreal cognitive assessment scale,MoCA)、简易智力状态检查量表(mini-mental state examination,MMSE)、阿尔茨海默病评定量表-认知量表(alzheimer's disease assessment scale-cognitive subscale,ADAS-cog)、肠道症状分级评分(gastroin-testinal symptom rating scale,GSRS)及脑脊液β淀粉样蛋白42(amyloidβ-42,Aβ-42)、磷酸化tau蛋白217(phosphorylated tau 217,P-tau217)含量及双侧海马体积,探究FC、FAT水平及GSRS评分与AD患者认知功能、双侧海马体积及Aβ-42、P-tau217蛋白含量的相关性。结果AD患者FC(102.20±36.58)、FAT(4.48±1.44)及血LPS(690.30±165.60)、LBP(10.70±3.31)水平均明显高于健康者(34.23±11.82、3.43±1.12、460.90±46.92、8.00±3.94),且差异有统计学意义(P均<0.05)。AD患者FC水平与MMSE(r=-0.33,P=0.02)、MoCA(r=-0.63,P<0.01)、脑脊液Aβ-42(r=-0.53,P<0.01)呈负相关,与ADAS-cog评分(r=0.35,P=0.01)、脑脊液P-tau217蛋白水平(r=0.37,P=0.01)呈正相关,差异有统计学意义。AD患者FAT水平与MoCA(r=-0.41,P<0.01)、脑脊液Aβ-42(r=-0.34,P=0.01)呈负相关,与ADAS-cog评分(r=0.42,P<0.01)、脑脊液P-tau217蛋白水平(r=0.34,P=0.01)呈正相关,差异有统计学意义。AD患者FC(r=-0.47)、FAT(r=-0.40)、LPS(r=-0.43)、LBP(r=-0.41)水平与左侧海马体积呈负相关,差异有统计学意义(P均<0.01)。AD患者GSRS评分与MMSE(r=-0.34,P=0.01)、MoCA(r=-0.51,P<0.01)评分呈负相关,与脑脊液P-tau217蛋白(r=0.37,P<0.01)呈正相关,差异均有统计学意义。结论AD患者肠道炎症相关指标水平增高,且升高程度与病情严重程度相关。
Objective To investigate the changes of intestinal inflammation related indicators and their correlation with disease severity in patients with Alzheimer's disease.Methods A total of 52 patients with alzheimer's disease(AD)and 60 healthy controls admitted to our hospital from August 2021 to March 2023 were selected in this prospective study,the levels of fecal calprotectin(FC),fecalα-1-antitrypsin(FAT),lipopolysaccharide(LPS)and lipopolysaccharide binding protein(LBP)in serum of AD patients and healthy controls were determined by ELISA method,the differences between the two groups were compared.The montreal cognitive assessment scale(MoCA),mini-mental state examination(MMSE),alzheimer's disease assessment scale-cognitive subscale(ADAS-cog),gastrointestinal symptom rating scale(GSRS),and the content of Aβ-42 and P-tau217protein in cerebrospinal fluid,and bilateral hippocampal volume of AD patients at admission were collected to explore the correlation between FC,FAT levels,GSRS score and cognitive dysfunction and bilateral hippocampal volume and the content of Aβ-42 and P-tau217 protein in cerebrospinal fluid in AD patients.Results The levels of FC(102.20±36.58),FAT(4.48±1.44),and serum LPS(690.30±165.60)and LBP(10.70±3.31)in AD patients were sig nificantly higher than those in healthy controls(34.23±11.82,3.43±1.12,460.90±46.92,8.00±3.94),and the difference was statistically significant(all P<0.O5).The levels of FC in AD patients were negatively correlated with MMSE score(r=-0.33,P=0.02),MoCA score(r=-0.63,P<0.01),the level of Aβ-42 in cerebrospinal fluid(r=-0.53,P<0.01),but positively correlated with ADAS-cog scores(r=0.35,P=0.01),the level of p tau217 protein(r=0.37,P=0.01),and the difference was statistically significant.FAT level was negatively correlated with MoCA(r=-0.41,P<0.01)and cerebrospinal fluid Aβ-42(r=-0.34,P=0.01),and was negatively correlated with ADAS-cog score(r=0.42,P<0.01)and cerebrospinal fluid p-tau217 protein level(r=0.34,P<0.01)in AD patients,and the difference was statistically significant.The levels of FC(r=-0.47),FAT(r=0.40),LPS(r=-0.43)and LBP(r=-0.41)were negatively correlated with the left hippocampal volume in AD patients,and the differences were statistically significant(all P<0.01).The GSRS score of AD patients was negatively correlatedwith MMSE(r=-0.34,P=0.01)and MoCA(r=-0.51,P<0.01)scores,and positively correlated with p-tau217 protein(r=0.37,P<0.01),and the difference was statistically significant.Conclusion The levels of intestinal inflammation related indexes in AD patients were increased,and the degree of increase is related to the severity of the disease.
作者
范文斐
刘冰
王春慧
郑世茹
任雅芳
张淑玲
FAN Wen-fei;LIU Bing;WANG Chun-hui;ZHENG Shi-ru;REN Ya-fang;ZHANG Shu-ling(Department of Neurology,the Fifth Clinical Medical College of Henan University of Traditional Chinese Medicine,Zhengzhou Peoples Hospital,Zhengzhou,Henan 450003,China)
出处
《医药论坛杂志》
2025年第20期2144-2149,共6页
Journal of Medical Forum
基金
河南省科技发展计划项目(182102310241)。
