循環(huán)中生物標記物與老年患者術后認知功能減退的相關性初步研究
發(fā)布時間：2018-09-09 18:01
【摘要】：【研究目的】研究術后認知功能減退組(POCD組)和非術后認知功能減退組(NPOCD組)術前(PREOP)、術后一天(POD1)、術后三天(POD3)患者外周血血漿中五種標記物(SOD1、SOD2、Osteopontin、Kallikrein-6、Contactin-1)的水平差異以及POCD組和NPOCD組內各時間點血漿中五種生物標記物(SOD1、SOD2、Osteopontin、Kallikrein-6、Contactin-1)水平的差異,進而探討外周血血漿中五種生物標記物的水平和POCD發(fā)生發(fā)展的關系,從而為POCD的早期診斷、治療和判斷預后提供可能的機制。【研究方法】選擇2015年10月-2016年4月在長海醫(yī)院麻醉科擇期行髖關節(jié)和膝關節(jié)置換術的老年患者進行前瞻性的臨床研究。本研究通過倫理委員會批準并且與患者簽署知情同意書。納入標準:年齡≥65歲、ASAⅠ-Ⅲ級、小學以上文化水平、術前MMSE評分≥22分、畫鐘表實驗(CDT)陰性。排除標準:ASAIII級、既往患有神經系統(tǒng)及精神方面疾病、腦卒中、惡性腫瘤、長期服用精神類藥品、術前嚴重焦慮、譫妄及失訪。本研究分為兩組,術后發(fā)生POCD(POCD組)和術后未發(fā)生POCD(NPOCD組)。并且記錄患者相關信息,包括:年齡、性別、身高、體重、身高體重指數(shù)(BMI)、既往病史、文化水平、手術時間、術前MMSE評分、術前焦慮評分、術后疼痛評分。術前我們應用SAS/SDS來排除嚴重焦慮和抑郁的患者,應用CAM-ICU量表排除譫妄,應用MMSE、畫鐘表實驗(CDT)評估患者基礎認知功能;術后一天(POD1)、術后三天(POD3)應用MMSE量表評估患者術后認知功能;術后一天(POD1)、術后三天(POD3)應用CAM-ICU量表排除譫妄;應用視覺模擬評分(VAS)評估術后疼痛。分別于PREOP、POD1、POD3采取入組患者空腹外周靜脈血存于抗凝管中。使用The MILLIPLEX?MAP Human Neurological Disorders Panel 3 kits(Millipore,Billerica,Massachusetts)檢測外周血血漿中的生物標記物的濃度�；颊邇山M間計量資料采用均數(shù)±標準差表示,計數(shù)資料采用頻數(shù)、百分比表示,實驗數(shù)據采用SPSS19.0統(tǒng)計軟件包進行數(shù)據結果分析。兩組間基本信息計量資料采用t檢驗,計數(shù)資料采用卡方檢驗。兩組生物標記物的水平整體比較采用重復測量資料方差分析,組內時間點兩兩比較采用LSD-t檢驗,同一時間點組間比較采用t檢驗,p0.05為差異有統(tǒng)計學意義。【結果】1.本研究共納入45例患者,18例(40%)患者在術后一天、三天均出現(xiàn)MMSE評分下降,且18例患者術后三天發(fā)生POCD,POCD組和NPOCD組兩組間患者基本特征差異無統(tǒng)計學意義(p0.05)。2.患者術前血漿中Kallikrein-6的基礎水平兩組間無顯著差異(p0.05),術后一天POCD組患者血漿中Kallikrein-6的水平顯著低于NPOCD組(p0.05),術后三天POCD組患者血漿中Kallikrein-6的水平顯著低于NPOCD組(p0.01),且POCD組患者術后一天、術后三天患者血漿中Kallikrein-6的水平均較術前顯著降低(p0.01)。3.患者術前、術后一天、術后三天血漿中l(wèi)n(SOD1)、ln(SOD2)、ln(Osteopontin)、Contactin-1的水平兩組間均無明顯差異(p0.05)。POCD組患者術后三天血漿中l(wèi)n(SOD1)的水平較術前顯著降低(p0.05);POCD組患者術后一天、術后三天患者血漿中l(wèi)n(Osteopontin)的水平均較術前顯著升高(p0.05);并且POCD組患者術后一天、術后三天患者血漿中Contactin-1的水平均較術前顯著降低(p0.01);而POCD組患者術后一天、術后三天血漿中l(wèi)n(SOD2)的水平與術前相比均無顯著差異(p0.05)。【結論】本研究發(fā)現(xiàn)18例(40%)擇期行髖關節(jié)和膝關節(jié)置換術的老年患者術后一天、術后三天均出現(xiàn)MMSE評分下降,且18例患者術后三天發(fā)生POCD。POCD組和NPOCD組兩組間患者基本特征差異無統(tǒng)計學意義。術后血漿中Kallikrein-6的水平可能與老年患者早期術后認知功能減退的發(fā)生發(fā)展相關,而POCD組患者血漿中標記物(SOD1、Osteopontin、Kallikrein-6、Contactin-1)的表達水平可能隨術后認知功能減退而不斷變化。
[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.
【學位授予單位】：第二軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R614
本文編號：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.
【學位授予單位】：第二軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R614
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