接受開心手術病患體內肝細胞生長因子的濃度變化

Serial Changes of Circulating Hepatocyte Growth Factor in Patients Undergoing Open Heart Surgery

徐莞曾(Wan-Tseng Hsu)

指導教授 ： 李啟明

國立臺灣大學/醫學院/臨床藥學研究所/碩士(2009年)

https://doi.org/10.6342/NTU.2009.01607

摘要

背景：
心臟異體移植血管病變 (cardiac allograft vasculopathy, CAV) 為心臟移植病患手術一年以後死亡之主因。已有研究指出，心臟移植病患血液循環中肝細胞生長因子 (hepatocyte growth factor，HGF) 濃度較高者，其CAV發生嚴重程度較低，但此HGF血液循環濃度升高現象是否受心臟移植手術本身所影響則未知。本試驗研究HGF於接受開心手術病患血液循環濃度的變化，作為後續應用HGF於CAV臨床治療之基礎。
方法：
受試者依據所接受之開心手術，分為使用體外循環 (cardiopulmonary bypass) 與未使用體外循環兩組，分別於開心手術前、開心手術後7天、30天、90天四個時間點，收集血液樣本；並將分離所得之血漿利用酵素連結免疫吸附分析方法 (Enzyme-linked immunosorbent assay, ELISA) 測量HGF濃度。獲得HGF濃度變化之初步結果後，再於開心手術後1天、5天、7天三個時間點收集血液樣本，分析HGF於手術後急性期之濃度變化。
結果：
肝細胞生長因子血漿濃度自手術前1296.1 ± 118.9 pg/mL，至手術後7天顯著升高至1820.2 ± 104.9 pg/mL (p < 0.05)，但於手術後30天已回至基礎值；且於手術後各個時間點，HGF濃度並未因手術中使用體外循環與否而有顯著差異。於開心手術後7天之急性期內，手術中使用體外循環者HGF濃度變化 (手術前為1569.10 ± 303.36 pg/mL；手術後第1天為4751.71 ± 971.28 pg/mL )則顯著高於未使用體外循環者(手術前為1131.16 ± 107.6 pg/mL；手術後第1天為 1970.98 ± 146.81 pg/mL，p < 0.05)。
結論：
開心手術趨使體內HGF濃度升高的影響於手術後30天已消失，故於心臟移植病患手術後一年體內HGF濃度與CAV嚴重程度的負相關性，已不受開心手術此變因的干擾。開心手術中使用體外循環增強手術後HGF濃度變化的現象，則需進一步收納相同病因的病人以釐清疾病本身的干擾。

關鍵字

肝細胞生長因子 ； 開心手術 ； 體外循環

並列摘要

Background— Cardiac allograft vasculopathy (CAV) is the leading cause of death after the first year in heart transplant recipients. An inverse correlation has been reported between circulating hepatocyte growth factor (HGF) levels and the severity of CAV. Before further application, the dynamically regulated production of HGF triggered by surgical insults after open heart surgery should be clarified.
Methods and Results— We investigated the serial change in plasma HGF levels in 50 patients undergoing open heart surgery. The patients were divided into two groups, depending on the use of cardiopulmonary bypass (CPB): CPB group and off-pump coronary artery bypass (OPCAB) group. For the initial 34 patients, the measurement time points were 7 (POD7), 30 (POD30), and 90 days postoperatively (POD90). The plasma HGF levels significantly increased from baseline (1296.1 ± 118.9 pg/mL) to 1820.2 ± 104.9 pg/mL (p < 0.05) on POD7, returning to baseline on POD30, and did not have any significant difference between groups at each time point. For the latter 16 patients, the measurement time points were 1(POD1), 5 (POD5), and 7 days postoperatively (POD7) in the postoperative acute phase. The response changes of plasma HGF levels were significantly higher in patients operated upon procedures requiring CPB.
Conclusions— High plasma HGF levels after open heart surgery may indicate the occurrence or necessity for tissue protection and regeneration after acute systemic insults with temporal effect fading out on the 30th postoperative day and thereafter. Thus the inverse correlation between circulating HGF levels and the severity of CAV detected by intravascular ultrasound at least 1 year after heart transplantation is not influenced by the duration post-operation. Further study is required to clarify the difference in response changes in plasma HGF levels during postoperative acute phase is made by CPB use or patient’s underlying disease indicated for surgical intervention.

並列關鍵字

hepatocyte growth factor ； open heart surgery ； cardiopulmonary bypass

參考文獻

1. Aylor DO, Edwards LB, Boucek MM, et al. Registry of the International Society for Heart and Lung Transplantation: twenty-third official adult heart transplantation report--2006. J Heart Lung Transplant 2006;25:869-79.

2. Avery RK. Cardiac-allograft vasculopathy. N Engl J Med 2003;349:829-30.

3. Kass M, Haddad H. Cardiac allograft vasculopathy: pathology, prevention and treatment. Curr Opin Cardiol 2006;21:132-7.

4. Matsumori A, Furukawa Y, Hashimoto T, et al. Increased circulating hepatocyte growth factor in the early stage of acute myocardial infarction. Biochem Biophys Res Commun 1996;221:391-5.

5. Morishita R, Aoki M, Hashiya N, et al. Therapeutic angiogenesis using hepatocyte growth factor (HGF). Curr Gene Ther 2004;4:199-206.