七氟烷对活体肾移植缺血再灌注损伤的作用研究
发布时间：2018-08-14 13:33
【摘要】：第一部分七氟烷预处理对活体肾移植缺血再灌注损伤的作用研究背景:肾移植术中供体肾脏接受热缺血和冷缺血两次打击,缺血再灌注损伤(ischaemic reperfusion injury,IRI)是肾移植术中不可避免的过程。而肾IRI与移植肾功能恢复、移植排斥反应以及移植肾慢性失功密切相关,是影响移植肾近期及长期预后、转归的关键因素。目前有动物实验和体外细胞研究证实七氟烷对肾IRI有保护作用,但七氟烷预处理(sevoflurane preconditioning,SpreC)对临床活体肾移植IRI有无保护作用尚不清楚。目的:观察SpreC对临床活体肾移植IRI的作用,从而研究七氟烷预处理是否具有肾脏保护作用。方法:2014年8月到2015年10月期间本院肾脏病中心行活体供肾同种异体肾移植术的病例60对(共120位患者)纳入本研究。根据供肾血管阻断前是否吸入七氟烷,随机分为Control和SpreC组,每组30对。供者、受者静脉诱导,全凭静脉维持麻醉,Control组:供者术中未给予七氟烷,使用丙泊酚维持麻醉;SpreC组:供者供肾血流阻断前30 min给予3%七氟烷吸入替代丙泊酚维持麻醉;两组受者术中均未用七氟烷。记录两组供、受者血流动力学变化;测定术后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)浓度,计算肾小球滤过率(eGFR);并在麻醉前,移植肾再灌注后3 h,6 h,24 h,72 h留取受者血标本,测定血中性粒细胞明胶酶相关载脂蛋白(NGAL)、白细胞介素-10(IL-10)和白细胞介素-1β(IL-1β)浓度;留取受者24 h尿量,测定24h尿蛋白和尿肌酐,并记录两组受者住院时间及住院期间并发症。结果:血流动力学指标的比较:供者间比较,与Control相比,3%的七氟烷吸入显著增加了 SpreC组预处理15 min、30 min时供者的心率(P0.05),但两组供者间各时点的平均动脉压无明显差异(P0.05)。受者间比较,两组受者间各时点平均动脉压和心率无明显差异(P0.05)。受者间肾功能的比较:两组受者术前及术后7天内各时点SCr、BUN、eGFR和Cys-C水平无显著性差异(P0.05);术后6 h SpreC组血浆NGAL水平明显高于Control组(P0.05),其余各时点两组间NGAL浓度无显著性差异;SpreC组术后第1天尿量显著少于Control组(P0.05);两组受者住院时间和住院期间并发症无显著性差异(P0.05)。受者间炎症反应指标的比较:两组受者术后血IL-10、IL-1β浓度和白细胞计数均较术前明显升高,但两组间各时点IL-10、IL-1β浓度无显著性差异(P0.05);术后第4天Control组白细胞计数高于SpreC组(P0.05),其余各时点两组间白细胞计数无显著性差异(P0.05)。结论:本研究结果显示SpreC对临床移植肾IRI无保护作用,并可能对移植肾术后功能恢复有一过性抑制作用。第二部分七氟烷后处理对活体肾移植缺血再灌注损伤的作用研究目的:观察七氟烷后处理(sevoflurane postconditioning,SpostC)对临床活体肾移植IRI的作用,从而研究七氟烷后处理是否具有肾脏保护作用。方法:2014年8月到2015年10月期间本院肾脏病中心行活体供肾同种异体肾移植术的病例60对(共120位患者)纳入本研究。根据移植肾复灌之初是否吸入七氟烷,随机分为Control和SpostC组,每组30对。所有病例静脉诱导,全凭静脉维持麻醉,Control组:受者术中未给予七氟烷,使用丙泊酚维持麻醉;SpostC组:受者在移植肾复灌之初30 min给予3%七氟烷吸入替代丙泊酚维持麻醉,两组供者术中未给予七氟烷。记录两组供、受者血流动力学变化,测定术后1-7天受者SCr、BUN、Cys-C浓度以及计算eGFR值;在麻醉前,移植肾再灌注后3h,6h,24h,72h留取受者血标本,测定血NGAL、IL-10和IL-1β浓度。留取受者24 h尿量,测定24 h尿蛋白和尿肌酐,并记录两组受者的住院时间及住院期间并发症。结果:血流动力学指标的比较:供者间比较,两组供者间各时点平均动脉压和心率无明显差异(P0.05)。受者间比较,与Control组相比,3%七氟烷导致了 SpostC组再灌注15 min时平均动脉压的显著降低和心率的明显增快(P0.001)。受者间肾功能的比较:两组受者术前及术后7天内各时点SCr、BUN、Cys-C和eGFR无显著性差异(P0.05);术后6 h SpostC组血浆NGAL水平明显高于Control组(P0.05),其余各时点两组间NGAL浓度无显著性差异;SpostC组再灌注后3 h及术后第1天尿量显著少于Control组(P0.05);两组受者住院时间和住院期间并发症无显著性差异(P0.05)。受者间炎症反应指标的比较:两组受者术后血IL-10和IL-1β浓度均较术前明显升高。与Control组相比,SpostC组IL-10浓度在术后3h、6 h时及24 h时升高更为显著(P0.05),而IL-1β浓度在术后6h较Control组有明显降低(P0.05);与此同时,SpostC组中性粒细胞计数术后第1、2、4天明显低于Control组(P0.05)。结论:本研究结果显示七氟烷具有抗炎作用,能调节活体肾移植术后炎症反应。但是,SpostC对临床移植肾IRI无保护作用,并可能对移植肾术后功能恢复有一过性抑制作用。第三部分七氟烷预处理和后处理对活体肾移植术后1年内预后的影响目的:探讨SpreC和SpostC对活体肾移植受者术后1年内肾功能和肾脏并发症的影响。方法:对2014年8月到2015年10月期间纳入第一部分和第二部分研究的Control、SpreC和SpostC组共90例受者,进行系统性随访1年,随访安排:术后半个月、1个月、3个月、6个月、12个月。随访主要内容:测定SCr、BUN、血红蛋白(hemoglobin,Hb)和血浆白蛋白(albumin,Alb)浓度并计算eGFR值。统计术后1年内急、慢性排异反应、移植肾失功、感染和肾炎复发等肾脏并发症的发生率。结果:三组受者术后1年内各时点SCr、BUN和eGFR无显著性差异(P0.05)。术后6个月、12个月时Control组Hb水平显著高于SpreC组(P0.01);术后3个月Control组Hb水平显著高于SpostC组(P0.05)。术后6个月、12个月Alb水平Control组亦高于SpostC组和SpreC组,但差异没有统计学意义(P0.05)。术后1年内肾脏并发症Control组(1例)低于SpreC组(8例)和SpostC(6例),但差异没有统计学意义。结论:本研究结果显示SpreC和SpostC对肾移植术后1年内的肾功能和肾脏并发症没明显影响。
[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.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R699.2
本文编号：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.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R699.2
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