Leptin与CXCL4在阿尔茨海默病发展进程中的作用研究

Study on the role of Leptin and CXCL4 in the development of Alzheimer′s disease

目的探讨瘦素(Leptin)与CXC趋化因子配体4(CXCL4)在阿尔茨海默病(AD)发展进程中的作用。方法选取2022年1-4月在南京医科大学附属江宁医院住院的AD患者30例为AD组,另选择同期健康体检者10例为健康对照组。采用酶联免疫吸附试验检测健康对照组与AD组血清β淀粉样蛋白1-42(Aβ1-42)、磷酸化tau-181蛋白(p-tau-181)、Leptin及CXCL4的表达水平并进行比较。取小鼠RAW264.7巨噬细胞,分别设置对照组(不进行任何处理)与处理组(采用50 ng/mL Leptin处理)。采用蛋白质免疫印迹法检测对照组及处理组Leptin处理6、12 h的巨噬细胞CXCL4蛋白表达水平并进行比较,采用实时荧光定量PCR检测对照组及处理组Leptin处理6、12 h的巨噬细胞CXCL4 mRNA表达水平并进行比较。分析AD患者血清CXCL4表达水平与Leptin表达水平的相关性。结果AD组血清Aβ1-42、p-tau-181表达水平均明显高于健康对照组,Leptin、CXCL4表达水平均明显低于健康对照组,差异有统计学意义(P<0.05)。与对照组比较,处理组Leptin处理6、12 h能够明显上调CXCL4蛋白表达水平,处理6 h能够明显上调CXCL4 mRNA表达水平,差异有统计学意义(P<0.05)。Pearson相关分析结果显示,AD患者血清Leptin表达水平与CXCL4表达水平呈正相关(r=0.445,P<0.05)。结论Leptin通过调控CXCL4的表达参与AD的发展。

Objective To explore the role of Leptin and CXC chemokine ligand 4(CXCL4)in the development of Alzheimer′s disease(AD).Methods Select 30 AD patients who were hospitalized in Jiangning Hospital Affiliated to Nanjing Medical University from January to April 2022 as the AD group,and 10 healthy people who were underwent physical examined in the same period as the healthy control group.Serum expression levels ofβ-amyloid 1-42(Aβ-1-42),phosphorylated tau-181(p-tau-181),Leptin and CXCL4 in the healthy control group and AD group were detected by enzyme-linked immunosorbent assay and compared.Mouse RAW264.7 macrophages were taken,and the control group(no treatment)and the treatment group(50 ng/mL Leptin treatment)were set up respectively.The expression level of CXCL4 protein in macrophages in the control group and the treatment group treated with Leptin for 6 and 12 h was detected by Western blot and compared.The expression level of CXCL4 mRNA in macrophages in the control group and the treatment group treated with Leptin for 6 and 12 h was detected by real-time fluorescence quantitative PCR and compared.The correlation between serum CXCL4 expression level and Leptin expression level in AD patients was analyzed.Results The expression levels of serum Aβ1-42 and p-tau-181 in the AD group were significantly higher than those in the healthy control group,and the expression levels of Leptin and CXCL4 in the AD group were significantly lower than those in the healthy control group,the differences were statistically significant(P<0.05).Leptin in the treatment group significantly up-regulated CXCL4 protein expression level after 6 and 12 h treatment,and up-regulated CXCL4 mRNA expression level after 6 h treatment,the differences were statistically significant(P<0.05).Pearson correlation analysis showed that there was a positive correlation between serum Leptin expression level and CXCL4 expression level in AD patients(r=0.445,P<0.05).Conclusion Leptin is involved in the development of AD by regulating CXCL4 expression.