七氟烷對活體腎移植缺血再灌注損傷的作用研究
發(fā)布時間：2018-08-14 13:33
【摘要】：第一部分七氟烷預處理對活體腎移植缺血再灌注損傷的作用研究背景:腎移植術(shù)中供體腎臟接受熱缺血和冷缺血兩次打擊,缺血再灌注損傷(ischaemic reperfusion injury,IRI)是腎移植術(shù)中不可避免的過程。而腎IRI與移植腎功能恢復、移植排斥反應以及移植腎慢性失功密切相關(guān),是影響移植腎近期及長期預后、轉(zhuǎn)歸的關(guān)鍵因素。目前有動物實驗和體外細胞研究證實七氟烷對腎IRI有保護作用,但七氟烷預處理(sevoflurane preconditioning,SpreC)對臨床活體腎移植IRI有無保護作用尚不清楚。目的:觀察SpreC對臨床活體腎移植IRI的作用,從而研究七氟烷預處理是否具有腎臟保護作用。方法:2014年8月到2015年10月期間本院腎臟病中心行活體供腎同種異體腎移植術(shù)的病例60對(共120位患者)納入本研究。根據(jù)供腎血管阻斷前是否吸入七氟烷,隨機分為Control和SpreC組,每組30對。供者、受者靜脈誘導,全憑靜脈維持麻醉,Control組:供者術(shù)中未給予七氟烷,使用丙泊酚維持麻醉;SpreC組:供者供腎血流阻斷前30 min給予3%七氟烷吸入替代丙泊酚維持麻醉;兩組受者術(shù)中均未用七氟烷。記錄兩組供、受者血流動力學變化;測定術(shù)后1-7天受者血肌酐(SCr)、尿素氮(BUN)、半胱氨酸蛋白酶抑制蛋白C(Cys-C)濃度,計算腎小球濾過率(eGFR);并在麻醉前,移植腎再灌注后3 h,6 h,24 h,72 h留取受者血標本,測定血中性粒細胞明膠酶相關(guān)載脂蛋白(NGAL)、白細胞介素-10(IL-10)和白細胞介素-1β(IL-1β)濃度;留取受者24 h尿量,測定24h尿蛋白和尿肌酐,并記錄兩組受者住院時間及住院期間并發(fā)癥。結(jié)果:血流動力學指標的比較:供者間比較,與Control相比,3%的七氟烷吸入顯著增加了 SpreC組預處理15 min、30 min時供者的心率(P0.05),但兩組供者間各時點的平均動脈壓無明顯差異(P0.05)。受者間比較,兩組受者間各時點平均動脈壓和心率無明顯差異(P0.05)。受者間腎功能的比較:兩組受者術(shù)前及術(shù)后7天內(nèi)各時點SCr、BUN、eGFR和Cys-C水平無顯著性差異(P0.05);術(shù)后6 h SpreC組血漿NGAL水平明顯高于Control組(P0.05),其余各時點兩組間NGAL濃度無顯著性差異;SpreC組術(shù)后第1天尿量顯著少于Control組(P0.05);兩組受者住院時間和住院期間并發(fā)癥無顯著性差異(P0.05)。受者間炎癥反應指標的比較:兩組受者術(shù)后血IL-10、IL-1β濃度和白細胞計數(shù)均較術(shù)前明顯升高,但兩組間各時點IL-10、IL-1β濃度無顯著性差異(P0.05);術(shù)后第4天Control組白細胞計數(shù)高于SpreC組(P0.05),其余各時點兩組間白細胞計數(shù)無顯著性差異(P0.05)。結(jié)論:本研究結(jié)果顯示SpreC對臨床移植腎IRI無保護作用,并可能對移植腎術(shù)后功能恢復有一過性抑制作用。第二部分七氟烷后處理對活體腎移植缺血再灌注損傷的作用研究目的:觀察七氟烷后處理(sevoflurane postconditioning,SpostC)對臨床活體腎移植IRI的作用,從而研究七氟烷后處理是否具有腎臟保護作用。方法:2014年8月到2015年10月期間本院腎臟病中心行活體供腎同種異體腎移植術(shù)的病例60對(共120位患者)納入本研究。根據(jù)移植腎復灌之初是否吸入七氟烷,隨機分為Control和SpostC組,每組30對。所有病例靜脈誘導,全憑靜脈維持麻醉,Control組:受者術(shù)中未給予七氟烷,使用丙泊酚維持麻醉;SpostC組:受者在移植腎復灌之初30 min給予3%七氟烷吸入替代丙泊酚維持麻醉,兩組供者術(shù)中未給予七氟烷。記錄兩組供、受者血流動力學變化,測定術(shù)后1-7天受者SCr、BUN、Cys-C濃度以及計算eGFR值;在麻醉前,移植腎再灌注后3h,6h,24h,72h留取受者血標本,測定血NGAL、IL-10和IL-1β濃度。留取受者24 h尿量,測定24 h尿蛋白和尿肌酐,并記錄兩組受者的住院時間及住院期間并發(fā)癥。結(jié)果:血流動力學指標的比較:供者間比較,兩組供者間各時點平均動脈壓和心率無明顯差異(P0.05)。受者間比較,與Control組相比,3%七氟烷導致了 SpostC組再灌注15 min時平均動脈壓的顯著降低和心率的明顯增快(P0.001)。受者間腎功能的比較:兩組受者術(shù)前及術(shù)后7天內(nèi)各時點SCr、BUN、Cys-C和eGFR無顯著性差異(P0.05);術(shù)后6 h SpostC組血漿NGAL水平明顯高于Control組(P0.05),其余各時點兩組間NGAL濃度無顯著性差異;SpostC組再灌注后3 h及術(shù)后第1天尿量顯著少于Control組(P0.05);兩組受者住院時間和住院期間并發(fā)癥無顯著性差異(P0.05)。受者間炎癥反應指標的比較:兩組受者術(shù)后血IL-10和IL-1β濃度均較術(shù)前明顯升高。與Control組相比,SpostC組IL-10濃度在術(shù)后3h、6 h時及24 h時升高更為顯著(P0.05),而IL-1β濃度在術(shù)后6h較Control組有明顯降低(P0.05);與此同時,SpostC組中性粒細胞計數(shù)術(shù)后第1、2、4天明顯低于Control組(P0.05)。結(jié)論:本研究結(jié)果顯示七氟烷具有抗炎作用,能調(diào)節(jié)活體腎移植術(shù)后炎癥反應。但是,SpostC對臨床移植腎IRI無保護作用,并可能對移植腎術(shù)后功能恢復有一過性抑制作用。第三部分七氟烷預處理和后處理對活體腎移植術(shù)后1年內(nèi)預后的影響目的:探討SpreC和SpostC對活體腎移植受者術(shù)后1年內(nèi)腎功能和腎臟并發(fā)癥的影響。方法:對2014年8月到2015年10月期間納入第一部分和第二部分研究的Control、SpreC和SpostC組共90例受者,進行系統(tǒng)性隨訪1年,隨訪安排:術(shù)后半個月、1個月、3個月、6個月、12個月。隨訪主要內(nèi)容:測定SCr、BUN、血紅蛋白(hemoglobin,Hb)和血漿白蛋白(albumin,Alb)濃度并計算eGFR值。統(tǒng)計術(shù)后1年內(nèi)急、慢性排異反應、移植腎失功、感染和腎炎復發(fā)等腎臟并發(fā)癥的發(fā)生率。結(jié)果:三組受者術(shù)后1年內(nèi)各時點SCr、BUN和eGFR無顯著性差異(P0.05)。術(shù)后6個月、12個月時Control組Hb水平顯著高于SpreC組(P0.01);術(shù)后3個月Control組Hb水平顯著高于SpostC組(P0.05)。術(shù)后6個月、12個月Alb水平Control組亦高于SpostC組和SpreC組,但差異沒有統(tǒng)計學意義(P0.05)。術(shù)后1年內(nèi)腎臟并發(fā)癥Control組(1例)低于SpreC組(8例)和SpostC(6例),但差異沒有統(tǒng)計學意義。結(jié)論:本研究結(jié)果顯示SpreC和SpostC對腎移植術(shù)后1年內(nèi)的腎功能和腎臟并發(fā)癥沒明顯影響。
[Abstract]:Part I Effects of sevoflurane preconditioning on ischemia-reperfusion injury in living kidney transplantation Background: The donor kidney is subjected to warm ischemia and cold ischemia during renal transplantation, and ischemia-reperfusion injury (IRI) is an inevitable process during renal transplantation. Sevoflurane preconditioning (SpreC) has a protective effect on IRI in living kidney transplantation, but it is not known whether sevoflurane preconditioning (SpreC) has a protective effect on IRI in living kidney transplantation. OBJECTIVE: To observe the effect of SpreC on IRI in living donor kidney transplantation, and to study whether sevoflurane preconditioning has renal protective effect. METHODS: Sixty cases (120 patients) of living donor kidney allograft transplantation in our renal disease center from August 2014 to October 2015 were included in this study. Sevoflurane inhalation was randomly divided into control group and preC group, 30 pairs in each group. Donor, recipient vein induction, total intravenous anesthesia, control group: donors did not give sevoflurane, use propofol to maintain anesthesia; Spre C group: donors were given 3% sevoflurane inhalation to replace propofol 30 minutes before the blockage of renal blood flow; both groups were given intraoperative anesthesia. Serum creatinine (SCr), urea nitrogen (BUN) and cysteine protease inhibitor protein C (Cys-C) were measured 1-7 days after operation, and glomerular filtration rate (eGFR) was calculated. Blood samples of recipients were taken before anesthesia and 3, 6, 24 and 72 hours after reperfusion. Enzyme-related apolipoprotein (NGAL), interleukin-10 (IL-10) and interleukin-1 beta (IL-1 beta) concentrations; 24-hour urinary volume, 24-hour urinary protein and creatinine were measured, and the length of hospital stay and complications were recorded. Results: Hemodynamic parameters: Compared with Control, 3% sevoflurane inhalation was significant. There was no significant difference in mean arterial pressure and heart rate between the two groups at each time point (P 0.05). There was no significant difference in mean arterial pressure and heart rate between the two groups (P 0.05). Comparison of renal function between the two groups: SCr, BUN at each time point before and 7 days after operation. There was no significant difference between eGFR and C ys-C levels (P 0.05); plasma NGAL levels in SpreC group were significantly higher than those in Control group at 6 h after operation (P 0.05), and there was no significant difference between the two groups at other time points; urine volume in SpreC group was significantly less than that in Control group on the first day after operation (P 0.05); there was no significant difference in hospitalization time and complications between the two groups (P 0.05). The levels of IL-10, IL-1 beta and white blood cell count in the two groups were significantly higher than those before operation, but there was no significant difference in the levels of IL-10 and IL-1 beta between the two groups at each time point (P 0.05); the white blood cell count in the Control group was higher than that in the Spre C group on the fourth day after operation (P 0.05), and there was no significant difference in the white blood cell count between the two groups at the other time points (P 0.05). 05. CONCLUSION: SpreC has no protective effect on clinical renal transplantation IRI and may have a transient inhibitory effect on functional recovery after renal transplantation. Methods: From August 2014 to October 2015, 60 patients (120 patients) who underwent living donor renal allograft transplantation in our Kidney Disease Center were randomly assigned to Con according to whether sevoflurane was inhaled at the beginning of renal reperfusion. All patients received intravenous induction and maintained anesthesia exclusively by intravenous anesthesia. Control group: Sevoflurane was not given during the operation and propofol was used to maintain anesthesia; Spost C group: 3% sevoflurane was given to replace propofol at the beginning of renal transplant reperfusion in 30 minutes, and sevoflurane was not given during the operation in both groups. Recipient hemodynamic changes were measured, SCr, BUN, Cys-C concentrations and eGFR values were measured at 1-7 days after operation, and blood samples were taken at 3, 6, 24 and 72 hours after reperfusion before anesthesia, and NGAL, IL-10 and IL-1 beta concentrations were measured. Results: There was no significant difference in mean arterial pressure and heart rate between the two groups (P 0.05). Compared with Control group, 3% sevoflurane resulted in a significant decrease in mean arterial pressure and a marked increase in heart rate at 15 min of reperfusion in Spost C group (P 0.001). Functional comparison: There was no significant difference in SCr, BUN, Cys-C and eGFR between the two groups before and 7 days after operation (P 0.05); plasma NGAL level in SpostC group was significantly higher than that in Control group at 6 hours after operation (P 0.05), and there was no significant difference in NGAL concentration between the two groups at other time points; urine volume in SpostC group was significantly less than that in Control group at 3 hours after reperfusion and 1 day after operation (P 0.05). There was no significant difference in the duration of hospitalization and complications between the two groups (P 0.05). Comparisons of inflammatory reaction between the two groups: The serum levels of IL-10 and IL-1 beta in the two groups were significantly higher than those before operation. Compared with the Control group, the concentration of IL-10 in the Spost C group increased significantly at 3, 6 and 24 hours after operation (P 0.05). At the same time, the number of neutrophils in SpostC group was significantly lower than that in Control group on the 1st, 2nd and 4th day after operation (P 0.05). Part III Effects of sevoflurane preconditioning and postconditioning on the prognosis of living donor kidney transplant recipients within one year Objective: To investigate the effects of SpreC and Post C on renal function and renal complications in living donor kidney transplant recipients within one year after transplantation. Ninety patients in the Control, SpreC and Post C groups were followed up for 1 year. The follow-up arrangements were as follows: 1 month, 1 month, 3 months, 6 months, 12 months after operation. Results: There was no significant difference in SCr, BUN and eGFR between the three groups at any time within 1 year after operation (P 0.05). Hb levels in control group were significantly higher than those in SpreC group at 6 months and 12 months after operation (P 0.01); Hb levels in control group were significantly higher than those in SpostC group at 3 months after operation (P 0.05). The monthly Alb level in control group was also higher than that in SpostC group and SpreC group, but the difference was not statistically significant (P 0.05). The renal complications in control group (1 case) were lower than that in SpreC group (8 cases) and postC group (6 cases), but the difference was not statistically significant. No obvious effect.
【學位授予單位】：浙江大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：R699.2
本文編號：2183015
[Abstract]:Part I Effects of sevoflurane preconditioning on ischemia-reperfusion injury in living kidney transplantation Background: The donor kidney is subjected to warm ischemia and cold ischemia during renal transplantation, and ischemia-reperfusion injury (IRI) is an inevitable process during renal transplantation. Sevoflurane preconditioning (SpreC) has a protective effect on IRI in living kidney transplantation, but it is not known whether sevoflurane preconditioning (SpreC) has a protective effect on IRI in living kidney transplantation. OBJECTIVE: To observe the effect of SpreC on IRI in living donor kidney transplantation, and to study whether sevoflurane preconditioning has renal protective effect. METHODS: Sixty cases (120 patients) of living donor kidney allograft transplantation in our renal disease center from August 2014 to October 2015 were included in this study. Sevoflurane inhalation was randomly divided into control group and preC group, 30 pairs in each group. Donor, recipient vein induction, total intravenous anesthesia, control group: donors did not give sevoflurane, use propofol to maintain anesthesia; Spre C group: donors were given 3% sevoflurane inhalation to replace propofol 30 minutes before the blockage of renal blood flow; both groups were given intraoperative anesthesia. Serum creatinine (SCr), urea nitrogen (BUN) and cysteine protease inhibitor protein C (Cys-C) were measured 1-7 days after operation, and glomerular filtration rate (eGFR) was calculated. Blood samples of recipients were taken before anesthesia and 3, 6, 24 and 72 hours after reperfusion. Enzyme-related apolipoprotein (NGAL), interleukin-10 (IL-10) and interleukin-1 beta (IL-1 beta) concentrations; 24-hour urinary volume, 24-hour urinary protein and creatinine were measured, and the length of hospital stay and complications were recorded. Results: Hemodynamic parameters: Compared with Control, 3% sevoflurane inhalation was significant. There was no significant difference in mean arterial pressure and heart rate between the two groups at each time point (P 0.05). There was no significant difference in mean arterial pressure and heart rate between the two groups (P 0.05). Comparison of renal function between the two groups: SCr, BUN at each time point before and 7 days after operation. There was no significant difference between eGFR and C ys-C levels (P 0.05); plasma NGAL levels in SpreC group were significantly higher than those in Control group at 6 h after operation (P 0.05), and there was no significant difference between the two groups at other time points; urine volume in SpreC group was significantly less than that in Control group on the first day after operation (P 0.05); there was no significant difference in hospitalization time and complications between the two groups (P 0.05). The levels of IL-10, IL-1 beta and white blood cell count in the two groups were significantly higher than those before operation, but there was no significant difference in the levels of IL-10 and IL-1 beta between the two groups at each time point (P 0.05); the white blood cell count in the Control group was higher than that in the Spre C group on the fourth day after operation (P 0.05), and there was no significant difference in the white blood cell count between the two groups at the other time points (P 0.05). 05. CONCLUSION: SpreC has no protective effect on clinical renal transplantation IRI and may have a transient inhibitory effect on functional recovery after renal transplantation. Methods: From August 2014 to October 2015, 60 patients (120 patients) who underwent living donor renal allograft transplantation in our Kidney Disease Center were randomly assigned to Con according to whether sevoflurane was inhaled at the beginning of renal reperfusion. All patients received intravenous induction and maintained anesthesia exclusively by intravenous anesthesia. Control group: Sevoflurane was not given during the operation and propofol was used to maintain anesthesia; Spost C group: 3% sevoflurane was given to replace propofol at the beginning of renal transplant reperfusion in 30 minutes, and sevoflurane was not given during the operation in both groups. Recipient hemodynamic changes were measured, SCr, BUN, Cys-C concentrations and eGFR values were measured at 1-7 days after operation, and blood samples were taken at 3, 6, 24 and 72 hours after reperfusion before anesthesia, and NGAL, IL-10 and IL-1 beta concentrations were measured. Results: There was no significant difference in mean arterial pressure and heart rate between the two groups (P 0.05). Compared with Control group, 3% sevoflurane resulted in a significant decrease in mean arterial pressure and a marked increase in heart rate at 15 min of reperfusion in Spost C group (P 0.001). Functional comparison: There was no significant difference in SCr, BUN, Cys-C and eGFR between the two groups before and 7 days after operation (P 0.05); plasma NGAL level in SpostC group was significantly higher than that in Control group at 6 hours after operation (P 0.05), and there was no significant difference in NGAL concentration between the two groups at other time points; urine volume in SpostC group was significantly less than that in Control group at 3 hours after reperfusion and 1 day after operation (P 0.05). There was no significant difference in the duration of hospitalization and complications between the two groups (P 0.05). Comparisons of inflammatory reaction between the two groups: The serum levels of IL-10 and IL-1 beta in the two groups were significantly higher than those before operation. Compared with the Control group, the concentration of IL-10 in the Spost C group increased significantly at 3, 6 and 24 hours after operation (P 0.05). At the same time, the number of neutrophils in SpostC group was significantly lower than that in Control group on the 1st, 2nd and 4th day after operation (P 0.05). Part III Effects of sevoflurane preconditioning and postconditioning on the prognosis of living donor kidney transplant recipients within one year Objective: To investigate the effects of SpreC and Post C on renal function and renal complications in living donor kidney transplant recipients within one year after transplantation. Ninety patients in the Control, SpreC and Post C groups were followed up for 1 year. The follow-up arrangements were as follows: 1 month, 1 month, 3 months, 6 months, 12 months after operation. Results: There was no significant difference in SCr, BUN and eGFR between the three groups at any time within 1 year after operation (P 0.05). Hb levels in control group were significantly higher than those in SpreC group at 6 months and 12 months after operation (P 0.01); Hb levels in control group were significantly higher than those in SpostC group at 3 months after operation (P 0.05). The monthly Alb level in control group was also higher than that in SpostC group and SpreC group, but the difference was not statistically significant (P 0.05). The renal complications in control group (1 case) were lower than that in SpreC group (8 cases) and postC group (6 cases), but the difference was not statistically significant. No obvious effect.
【學位授予單位】：浙江大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：R699.2
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