循环中生物标记物与老年患者术后认知功能减退的相关性初步研究
发布时间：2018-09-09 18:01
【摘要】：【研究目的】研究术后认知功能减退组(POCD组)和非术后认知功能减退组(NPOCD组)术前(PREOP)、术后一天(POD1)、术后三天(POD3)患者外周血血浆中五种标记物(SOD1、SOD2、Osteopontin、Kallikrein-6、Contactin-1)的水平差异以及POCD组和NPOCD组内各时间点血浆中五种生物标记物(SOD1、SOD2、Osteopontin、Kallikrein-6、Contactin-1)水平的差异,进而探讨外周血血浆中五种生物标记物的水平和POCD发生发展的关系,从而为POCD的早期诊断、治疗和判断预后提供可能的机制。【研究方法】选择2015年10月-2016年4月在长海医院麻醉科择期行髋关节和膝关节置换术的老年患者进行前瞻性的临床研究。本研究通过伦理委员会批准并且与患者签署知情同意书。纳入标准:年龄≥65岁、ASAⅠ-Ⅲ级、小学以上文化水平、术前MMSE评分≥22分、画钟表实验(CDT)阴性。排除标准:ASAIII级、既往患有神经系统及精神方面疾病、脑卒中、恶性肿瘤、长期服用精神类药品、术前严重焦虑、谵妄及失访。本研究分为两组,术后发生POCD(POCD组)和术后未发生POCD(NPOCD组)。并且记录患者相关信息,包括:年龄、性别、身高、体重、身高体重指数(BMI)、既往病史、文化水平、手术时间、术前MMSE评分、术前焦虑评分、术后疼痛评分。术前我们应用SAS/SDS来排除严重焦虑和抑郁的患者,应用CAM-ICU量表排除谵妄,应用MMSE、画钟表实验(CDT)评估患者基础认知功能;术后一天(POD1)、术后三天(POD3)应用MMSE量表评估患者术后认知功能;术后一天(POD1)、术后三天(POD3)应用CAM-ICU量表排除谵妄;应用视觉模拟评分(VAS)评估术后疼痛。分别于PREOP、POD1、POD3采取入组患者空腹外周静脉血存于抗凝管中。使用The MILLIPLEX?MAP Human Neurological Disorders Panel 3 kits(Millipore,Billerica,Massachusetts)检测外周血血浆中的生物标记物的浓度。患者两组间计量资料采用均数±标准差表示,计数资料采用频数、百分比表示,实验数据采用SPSS19.0统计软件包进行数据结果分析。两组间基本信息计量资料采用t检验,计数资料采用卡方检验。两组生物标记物的水平整体比较采用重复测量资料方差分析,组内时间点两两比较采用LSD-t检验,同一时间点组间比较采用t检验,p0.05为差异有统计学意义。【结果】1.本研究共纳入45例患者,18例(40%)患者在术后一天、三天均出现MMSE评分下降,且18例患者术后三天发生POCD,POCD组和NPOCD组两组间患者基本特征差异无统计学意义(p0.05)。2.患者术前血浆中Kallikrein-6的基础水平两组间无显著差异(p0.05),术后一天POCD组患者血浆中Kallikrein-6的水平显著低于NPOCD组(p0.05),术后三天POCD组患者血浆中Kallikrein-6的水平显著低于NPOCD组(p0.01),且POCD组患者术后一天、术后三天患者血浆中Kallikrein-6的水平均较术前显著降低(p0.01)。3.患者术前、术后一天、术后三天血浆中ln(SOD1)、ln(SOD2)、ln(Osteopontin)、Contactin-1的水平两组间均无明显差异(p0.05)。POCD组患者术后三天血浆中ln(SOD1)的水平较术前显著降低(p0.05);POCD组患者术后一天、术后三天患者血浆中ln(Osteopontin)的水平均较术前显著升高(p0.05);并且POCD组患者术后一天、术后三天患者血浆中Contactin-1的水平均较术前显著降低(p0.01);而POCD组患者术后一天、术后三天血浆中ln(SOD2)的水平与术前相比均无显著差异(p0.05)。【结论】本研究发现18例(40%)择期行髋关节和膝关节置换术的老年患者术后一天、术后三天均出现MMSE评分下降,且18例患者术后三天发生POCD。POCD组和NPOCD组两组间患者基本特征差异无统计学意义。术后血浆中Kallikrein-6的水平可能与老年患者早期术后认知功能减退的发生发展相关,而POCD组患者血浆中标记物(SOD1、Osteopontin、Kallikrein-6、Contactin-1)的表达水平可能随术后认知功能减退而不断变化。
[Abstract]:[Objective] To study the difference of five markers (SOD1, SOD2, Osteopontin, Kallikrein-6, Contactin-1) in peripheral blood plasma of patients with postoperative cognitive impairment (POCD) and non-postoperative cognitive impairment (NPOCD) before surgery (PREOP), one day after surgery (POD1), and three days after surgery (POD3), and the blood levels of POCD and NPOCD at different time points. The differences of plasma levels of five biomarkers (SOD1, SOD2, Osteopontin, Kallikrein-6, Contactin-1) were studied to explore the relationship between the levels of five biomarkers in peripheral blood plasma and the occurrence and development of POCD, thus providing a possible mechanism for the early diagnosis, treatment and prognosis of POCD. [Methods] Oct. 2015-2014 was selected as the study area. A prospective clinical study was conducted in elderly patients undergoing elective hip and knee arthroplasty in the anesthesiology department of Changhai Hospital in June. The study was approved by the Ethics Committee and informed consent was signed with the patients. Negative. Exclusive criteria: ASAIII, previous neurological and psychiatric disorders, stroke, malignant tumor, long-term psychotropic drugs, preoperative severe anxiety, delirium and loss of visit. This study was divided into two groups, POCD (POCD group) occurred after surgery and no POCD (NPOCD group) occurred after surgery. Preoperative SAS / SDS was used to exclude patients with severe anxiety and depression, CAM - ICU was used to exclude delirium, MMSE and CDT were used to evaluate the patients'basic cognitive function. Postoperative cognitive function was assessed with MMSE on day 1 (POD1) and day 3 (POD3); delirium was excluded by CAM-ICU on day 1 (POD1) and postoperative pain was assessed by visual analogue scale (VAS). Fasting peripheral venous blood was stored in anticoagulant tubes on day 1 (POD1) and day 3 (POD3). The MILLIPLEX?MAP H was used. The concentration of biomarkers in peripheral blood plasma was measured by the uman Neurological Disorders Panel 3 kits (Millipore, Billerica, Massachusetts). The measurements between the two groups were expressed by mean (+) standard deviation. The counts were expressed by frequency and percentage. The experimental data were analyzed by SPSS19.0 statistical software package. The basic information was measured by t-test, and the counting data by chi-square test. The levels of biomarkers in the two groups were compared by analysis of variance of repeated measurements. The time points in the two groups were compared by LSD-t test, and the time points in the same group were compared by t-test. Among 45 patients, 18 (40%) had a decrease in MMSE score one day and three days after surgery, and there was no significant difference in the basic characteristics between the POCD group and NPOCD group (p0.05). 2. There was no significant difference in the baseline level of Kallikrein-6 in the preoperative plasma between the two groups (p0.05). The plasma levels of Kallikrein-6 in POCD group were significantly lower than those in NPOCD group (p0.05). The plasma levels of Kallikrein-6 in POCD group were significantly lower than those in NPOCD group three days after operation (p0.01). The plasma levels of Kallikrein-6 in POCD group were significantly lower than those in NPOCD group one day after operation and three days after operation (p0.01). 3. The levels of LN (SOD1), ln (SOD2), ln (Osteopontin) and Contactin-1 were not significantly different between the two groups (p0.05). The levels of LN (SOD1) in plasma of POCD group were significantly lower than those of pre-operation three days after operation (p0.05); the levels of LN (Osteopontin) in plasma of POCD group were significantly higher than those of pre-operation one day and three days after operation (p0.05). The plasma levels of Contactin-1 were significantly lower one day and three days after surgery than those before surgery (p0.01), but there was no significant difference in the plasma levels of LN (SOD2) between the POCD group and the preoperative group on the first day and three days after surgery (p0.05). [Conclusion] 18 (40%) elderly patients undergoing hip and knee arthroplasty were found in this study. There was no significant difference in the basic characteristics between the POCD. POCD group and NPOCD group. The level of Kallikrein-6 in plasma after surgery may be related to the occurrence and development of early postoperative cognitive impairment in elderly patients, while the level of plasma markers in POCD group (P The expression levels of SOD1, Osteopontin, Kallikrein-6 and Contactin-1 may change with postoperative cognitive impairment.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R614
本文编号：2233149
[Abstract]:[Objective] To study the difference of five markers (SOD1, SOD2, Osteopontin, Kallikrein-6, Contactin-1) in peripheral blood plasma of patients with postoperative cognitive impairment (POCD) and non-postoperative cognitive impairment (NPOCD) before surgery (PREOP), one day after surgery (POD1), and three days after surgery (POD3), and the blood levels of POCD and NPOCD at different time points. The differences of plasma levels of five biomarkers (SOD1, SOD2, Osteopontin, Kallikrein-6, Contactin-1) were studied to explore the relationship between the levels of five biomarkers in peripheral blood plasma and the occurrence and development of POCD, thus providing a possible mechanism for the early diagnosis, treatment and prognosis of POCD. [Methods] Oct. 2015-2014 was selected as the study area. A prospective clinical study was conducted in elderly patients undergoing elective hip and knee arthroplasty in the anesthesiology department of Changhai Hospital in June. The study was approved by the Ethics Committee and informed consent was signed with the patients. Negative. Exclusive criteria: ASAIII, previous neurological and psychiatric disorders, stroke, malignant tumor, long-term psychotropic drugs, preoperative severe anxiety, delirium and loss of visit. This study was divided into two groups, POCD (POCD group) occurred after surgery and no POCD (NPOCD group) occurred after surgery. Preoperative SAS / SDS was used to exclude patients with severe anxiety and depression, CAM - ICU was used to exclude delirium, MMSE and CDT were used to evaluate the patients'basic cognitive function. Postoperative cognitive function was assessed with MMSE on day 1 (POD1) and day 3 (POD3); delirium was excluded by CAM-ICU on day 1 (POD1) and postoperative pain was assessed by visual analogue scale (VAS). Fasting peripheral venous blood was stored in anticoagulant tubes on day 1 (POD1) and day 3 (POD3). The MILLIPLEX?MAP H was used. The concentration of biomarkers in peripheral blood plasma was measured by the uman Neurological Disorders Panel 3 kits (Millipore, Billerica, Massachusetts). The measurements between the two groups were expressed by mean (+) standard deviation. The counts were expressed by frequency and percentage. The experimental data were analyzed by SPSS19.0 statistical software package. The basic information was measured by t-test, and the counting data by chi-square test. The levels of biomarkers in the two groups were compared by analysis of variance of repeated measurements. The time points in the two groups were compared by LSD-t test, and the time points in the same group were compared by t-test. Among 45 patients, 18 (40%) had a decrease in MMSE score one day and three days after surgery, and there was no significant difference in the basic characteristics between the POCD group and NPOCD group (p0.05). 2. There was no significant difference in the baseline level of Kallikrein-6 in the preoperative plasma between the two groups (p0.05). The plasma levels of Kallikrein-6 in POCD group were significantly lower than those in NPOCD group (p0.05). The plasma levels of Kallikrein-6 in POCD group were significantly lower than those in NPOCD group three days after operation (p0.01). The plasma levels of Kallikrein-6 in POCD group were significantly lower than those in NPOCD group one day after operation and three days after operation (p0.01). 3. The levels of LN (SOD1), ln (SOD2), ln (Osteopontin) and Contactin-1 were not significantly different between the two groups (p0.05). The levels of LN (SOD1) in plasma of POCD group were significantly lower than those of pre-operation three days after operation (p0.05); the levels of LN (Osteopontin) in plasma of POCD group were significantly higher than those of pre-operation one day and three days after operation (p0.05). The plasma levels of Contactin-1 were significantly lower one day and three days after surgery than those before surgery (p0.01), but there was no significant difference in the plasma levels of LN (SOD2) between the POCD group and the preoperative group on the first day and three days after surgery (p0.05). [Conclusion] 18 (40%) elderly patients undergoing hip and knee arthroplasty were found in this study. There was no significant difference in the basic characteristics between the POCD. POCD group and NPOCD group. The level of Kallikrein-6 in plasma after surgery may be related to the occurrence and development of early postoperative cognitive impairment in elderly patients, while the level of plasma markers in POCD group (P The expression levels of SOD1, Osteopontin, Kallikrein-6 and Contactin-1 may change with postoperative cognitive impairment.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R614
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