脑小血管病患者血清Klotho,FGF23表达水平变化与疾病进展及认知功能障碍的相关性分析

目的 探讨脑小血管病(Cerebral small vascular disease,CSVD)患者血清Klotho蛋白、成纤维细胞生长因子23(Fibroblast growth factor 23,FGF23)表达水平变化与疾病进展及认知功能障碍的相关性。方法 选取2017年2月-2020年2月本院收治的CSVD患者80例为研究对象,同期选取40例体检健康人群为对照组,根据CSVD患者脑动脉搏动指数(Pulsatility index,PI)将其分为轻度组23例(PI<1.0)、中度组36例(1.0≤PI<1.5)和重度组21例(PI≥1.5); 根据蒙特利尔认知评估量表(Montreal cognitive assessment scale,MoCA)评分将其分为伴认知功能障碍组32例(MoCA评分<26分)和无认知功能障碍组48例(MoCA评分≥26分); 采用酶联免疫吸附法(Enzyme-linked immunosorbent assay,ELISA)检测血清Klotho,FGF23蛋白水平; 利用Pearson法分析CSVD患者血清Klotho,FGF23水平与MoCA评分的相关性; 利用多因素Logistic分析影响CSVD患者发生认知功能障碍的危险因素。结果 研究组患者MoCA评分、Klotho水平明显低于对照组(P=0.000),FGF23水平明显高于对照组(P=0.000)。随CSVD患者病情严重程度加重,轻度组、中度组、重度组血清Klotho(491.23±116.34)、(417.51±107.57)、(332.87±92.36)pg/mL]水平逐渐降低(P均<0.05),FGF23(447.83±97.42)、(512.74±119.67)、(627.32±127.43)pg/mL]水平逐渐升高(P均<0.05)。与无认知功能障碍组患者比较,伴认知功能障碍组CSVD患者血清Klotho水平(347.62±95.24)比(462.50±107.06)pg/mL]明显降低,FGF23水平(580.29±120.54)比(492.68±107.34)pg/mL]明显升高(P<0.05)。Pearson法分析显示,CSVD患者血清Klotho水平与MoCA评分呈正相关(r=0.611,P=0.000),FGF23水平与MoCA评分呈负相关(r=-0.607,P=0.000)。多因素Logistic回归分析显示,Klotho水平、FGF23水平是CSVD患者发生认知功能障碍的独立影响因素(P均<0.01)。结论 随CSVD患者病情加重,血清Klotho水平逐渐降低,FGF23水平逐渐升高,且与患者认知功能障碍密切相关。

Correlation analysis of serum Klotho and FGF23 expression with disease progression and cognitive dysfunction in patients with cerebral small vessel disease

ObjectiveTo investigate the relationship between the expression of serum Klotho protein and fibroblast growth factor 23(FGF23)and disease progression and cognitive dysfunction in patients with cerebral small vessel disease(CSVD).Methods A total of 80 CSVD patients in our hospital from February 2017 to February 2020 were selected as the research objects, and 40 healthy people were selected as the healthy control group. According to the cerebral artery pulsatility index(PI), CSVD patients were divided into mild group(23 cases, PI<1.0), moderate group(36 cases, 1.0≤PI<1.5)and severe group(21 cases, PI≥1.5). According to the Montreal Cognitive Assessment Scale(MoCA), CSVD patients were also divided into cognitive impairment group(32 cases, MoCA score<26)and non cognitive impairment group(48 cases, MoCA score≥26). Enzyme linked immunosorbent assay(ELISA)was used to detect the serum Klotho and FGF23 protein levels, and the differences of serum Klotho and FGF23 levels in each group were compared. Pearson method was used to analyze the correlation between serum Klotho, FGF23 levels and MOCA score in CSVD patients. Multivariate Logistic analysis was used to analyze the risk factors of cognitive dysfunction in CSVD patients.Results The MOCA score and Klotho level in study group were significantly lower than those in control group(P=0.000), but FGF23 level was significantly higher than that in control group(P=0.000). With increasing severity of CSVD, the serum Klotho level (491.23±116.34)pg·mL^-1 vs.(417.51±107.57)pg·mL^-1 vs.(332.87±92.36)pg·mL^-1] was decreased gradually in mild, moderate and severe groups(all P<0.05), and FGF23 (447.83±97.42)pg·mL^-1 vs.(512.74±119.67)pg·mL^-1 vs.(627.32±127.43)pg·mL^-1] was increased gradually(P<0.05). Compared with those in non cognitive impairment group, the serum Klotho level (347.62±95.24)pg·mL^-1 vs.(462.50±107.06)pg·mL^-1] was significantly lower, and FGF23 level (580.29±120.54)pg·mL^-1 vs.(492.68±107.34)pg·mL^-1] was significantly higher in cognitive impairment group(P<0.05). Pearson results showed that serum Klotho level was positively correlated with MOCA score(r=0.611, P=0.000), and FGF23 level was negatively correlated with MOCA score(r=-0.607, P=0.000). Multivariate Logistic regression analysis showed that Klotho level and FGF23 level were both independent influencing factors of cognitive dysfunction in CSVD patients(all P<0.01).Conclusion With the aggravation of CSVD, the level of serum Klotho was decreased gradually and the level of FGF23 was increased gradually, and they were closely related to cognitive dysfunction.