Prostaglandin E1 administration post liver transplantation and renal outcomes:A retrospective single center experience

BACKGROUND Prostaglandin E1(PGE1),or alprostadil,is a potent vasodilator that improves hepatic blood flow and reduces ischemia-reperfusion injury post-liver transplantation(LT).However,the benefits of PGE1 on renal function after LT have not yet been well described.AIM To assess the impact of PGE1 administration on renal function in patients who underwent liver or liver-kidney transplant.METHODS This retrospective study included all patients who underwent liver or liverkidney transplant at our institution from January,2011 to December,2021.Patients were classified based on whether they received PGE1.PGE1 was administered post-LT to those with transaminases>1000 U/L in the immediate postoperative period.Demographics,post-LT treatments and/or complications,renal function,and survival were analyzed.Multivariable logistic regression analysis was performed,and a two-tailed P value<0.05 was considered statistically significant.RESULTS A total of 145 patients underwent LT,with 44(30%)receiving PGE1.Baseline patient characteristics were comparable,except the PGE1 group had significantly higher aspartate aminotransferase(AST)(1961.9 U/L±1862.3 U/L vs 878 U/L±741.4 U/L,P=0.000),alanine aminotransferase(1070.6 U/L±895 U/L vs 547.7 U/L±410 U/L,P=0.000),international normalized ratio on post-LT day 1(2±0.74 vs 1.8±0.4,P=0.03),a longer intensive care unit stay(8.1 days±11.8 days vs 3.8 days±4.6 days,P=0.003),more vasopressor use(55.53 hours±111 hours vs 16.33 hours±26.3 hours,P=0.002),and higher immediate postoperative complications(18.6%vs 4.9%,P=0.04).The PGE1 group also had a significantly higher 90-day readmission rate(29.6%vs 13.1%,P=0.02)and lower 1-year liver graft survival(87.5%vs 98.9%,P=0.005).However,30-day readmission(31.6%vs 27.4%,P=0.64),LT complications(hepatic artery thrombosis,biliary complications,rejection of liver graft,cardiomyopathy),1-year patient survival(96.9%vs 97.8%,P=0.77),overall liver graft survival,and overall patient survival were similar between the two groups(95.4%vs 93.9%,P=0.74 and 88.4%vs 86.9%,P=0.81 respectively).Although the PGE1 group had a significantly lower glomerular filtration rate(eGFR)on post-LT day 7(46.3 mL/minute±26.7 mL/minute vs 62.5 mL/minute±34 mL/minute,P=0.009),the eventual need for renal replacement therapy(13.6%vs 5.9%,P=0.09),the number of dialysis sessions(0.91 vs 0.27,P=0.13),and eGFR at 1-month(37.2 mL/minute±35.9 mL/minute vs 42 mL/minute±36.9 mL/minute,P=0.49),6-months(54.8 mL/minute±21.6 mL/minute vs 62 mL/minute±21.4 mL/minute,P=0.09),and 12-months(63.7 mL/minute±20.7 mL/minute vs 62.8 mL/minute±20.3 mL/minute,P=0.85)post-LT were similar to those in the non-PGE1 group.CONCLUSION In patients who received PGE1 for ischemia-reperfusion injury,despite immediate acute renal injury post-LT,the renal function at 1-month,6-months,and 12-months post-LT was similar compared to those without ischemiareperfusion injury.Prospective clinical trials are needed to further elucidate the benefits of PGE1 use in renal function.

Intra-arterial lipo-prostaglandin E1 infusion for arterial spasm in liver transplantation:A case report

BACKGROUND Hepatic artery obstruction is a critical consideration in graft outcomes after living donor liver transplantation.We report a case of diffuse arterial vasospasm that developed immediately after anastomosis and was managed with an intra-arterial infusion of lipo-prostaglandin E1(PGE1).CASE SUMMARY A 57-year-old male with hepatitis B virus-related liver cirrhosis and hepatocellular carcinoma underwent ABO-incompatible living donor liver transplant.The grafted hepatic artery was first anastomosed to the recipient’s right hepatic artery stump.However,the arterial pulse immediately weakened.Although a new anastomosis was performed using the right gastroepiploic artery,the patient’s arterial pulse rate remained poor.We attempted angiographic intervention immediately after the operation;it showed diffuse arterial vasospasms like‘beads on a string’.We attempted continuous infusion of lipo-PGE1 overnight via an intra-arterial catheter.The next day,arterial flow improved without any spasms or strictures.The patient had no additional arterial complications or related sequelae at the time of writing,1-year post-liver transplantation.CONCLUSION Angiographic evaluation is helpful in cases of repetitive arterial obstruction,and intra-arterial infusion of lipo-PGE1 may be effective in treating diffuse arterial spasms.

EFFECTS OF PROSTAGLANDIN E1 ON THE PROGRESSION OF ARISTOLOCHIC ACID NEPHROPATHY

Objective To investigate the effects of prostaglandin E1 (PGE1) on the progression of aristolochic acid nephropathy (AAN). Methods Twenty-four patients diagnosed as AAN with serum creatinine (Scr) between 1.5 mg/dL and 4 mg/dL during September 2001 to August 2003 were randomly divided into 2 groups. All patients had ingested long dan xie gan wan con-taining aristolochic acid (0.219 mg/g) for at least 3 months. Twelve patients were injected with Alprostadil (10 μg/d for 10 days in one month, summing up to 6 months). Except for PGE1, the other therapy was same in both groups. Renal function was assessed using reciprocal serum creatinine levels (1/Scr). Results The level of Scr and serum hemoglobin (Hgb) was similar in both groups prior to therapy. During follow-up, 1/Scr levels in PGE1 group were significantly higher than control group (P < 0.01), and Hgb levels in PGE1 group were sig-nificantly increased compared with control (P < 0.05).Conclusion PGE1 can slow the progression of renal failure and increase Hgb level of AAN patient.

Protective effects of prostaglandin E1 perfusion againstspinal cord ischemia-reperfusion injury in a rabbit model

BACKGROUND： Prostaglandin E1 （PGE1） is known to be protective in ischemia-reperfusion of heart, lung,renal, and liver tissue. It still remains to be determined whether PGE1 exhibits similar protection against spinal cord ischemia-reperfusion injury in a rabbit model. OBJECTIVE： To observe the large, ventral horn, motor neurons of the spinal cord, as well as limb function, and to investigate whether perfusion of PGE1 exhibits protective effects against spinal cord ischemia-reperfusion injury in a rabbit model. DESIGN, TIME AND SETTING： Controlled observation. The experiment was performed at the Department of Orthopedics, First Affiliated Hospital of Liaoning Medical University between June and October 2007. MATERIALS： Twenty male, New Zealand white rabbits, weighing 2.0 kg and of mixed gender, were used in the present study. The following chemicals and compounds were used： prostaglandin E1 injectable powder,as well as malondialdehyde and ATPase kits. Animal intervention was in accordance with animal ethical standards. METHODS： We separated rabbits into control and experimental groups randomly, with 10 rabbits in each group. Rabbits were used as spinal cord ischemia models by segmentally cross-clamping the infrarenal aorta. The control group was subsequently perfused for five minutes with blood and saline solution, and the experimental group was perfused for 5 minutes with blood and saline solution containing PGE1 （100 ng/kg/min）. MAIN OUTCOME MEASURES： The neurological function of the hind limbs was assessed 12, 24, and 48 hours after model establishment. All animals were sacrificed and spinal cords were harvested for histological analyses. The large motor neurons in the ventral horn of L1-7 were observed by inverted microscope. RESULTS： All 20 rabbits were included in the final analysis, without any loss. In the ventral horn of the L5-7 segments, there were more large motor neurons that appeared viable in the experimental group than the control group （P 〈 0.05）. The scores of hind limb functions were greater in the experimental group after 12, 24, and 48 hours （P 〈 0.01）. CONCLUSION： Perfusion of PGE1 reduced the amount of neuronal damage in the spinal cord ischemia-reperfusion injury rabbit model. These results correlated with increased numbers large motor neurons in the ventral horn of the spinal cord, as well as improved hind limb function.

Does perioperative prostaglandin E1 affect survival of patients with esophageal cancer?

AIM: To detect the effect of intraoperative prostaglandin E1 (PGE1) infusion on survival of esophagectomized patients due to cancer. METHODS: In this preliminary study, a double blinded placebo based clinical trial was performed. Thirty patients with esophageal cancer scheduled for esophagectomy via the transthoracic approach were randomized by a block randomization method, in two equal groups: PGE1 group - infusion of PGE1 (20 ng/kg per minute) in the operating room and placebo group - saline 0.9% with the same volume and rate. The infusion began before induction of anesthesia and finished just before transfer to the intensive care unit. The patients, anesthetist, intensive care physicians, nurses and surgeons were blinded to both study groups. All the patients were anesthetized with the same method. For postoperative pain control, a thoracic epidural catheter was placed for all patients before induction of anesthesia. We followed up the patients until October 2010. Basic characteristics, duration of anesthesia, total surgery and thoracotomy time, preoperative hemoglobin, length of tumor, grade of histological differentiation, disease stage, number of lymph nodes in the resected mass, number of readmissions to hospital, total duration of readmission and survival rates were compared between the two groups. Some of the data originates from the historical data reported in our previous study. We report them for better realization of the follow up results. RESULTS: The patients’ characteristics and perioperative variables were compared between the two groups. There were no significant differences in age (P = 0.48), gender (P = 0.27), body mass index (P = 0.77), American Society of Anesthesiologists physical status more than?I?(P = 0.71), and smoking (P = 0.65). The PGE1 and placebo group were comparable in the following variables: duration of anesthesia (277 ± 50 vs 270 ± 67, P = 0.86), duration of thoracotomy (89 ± 35 vs 96 ± 19, P = 0.46), duration of operation (234 ± 37 vs 240 ± 66, P = 0.75), volume of blood loss during operation (520 ± 130 vs 630 ± 330, P = 0.34), and preoperative hemoglobin (14.4 ± 2 vs 14.7 ± 1.9, P = 0.62), respectively. No hemodynamic complications requiring an infusion of dopamine or cessation of the PGE1 infusion were encountered. Cancer variables were compared between the PGE1 and placebo group. Length of tumor (11.9 ± 3 vs 12.3 ± 3, P = 0.83), poor/undifferentiated grade of histological differentiation [3 (20%) vs 3 (20%), P = 0.78], disease stage III [5 (33.3%), 4 (26.7%), P = 0.72] and more than 3 lymph nodes in the resected mass [3 (20%) vs 2 (13.3%), P = 0.79] were similar in both groups. All the patients were discharged from hospital except one patient in the control group who died because of a post operative myocardial infarction. No life threatening postoperative complication occurred in any patient. The results of outcome and survival were the same in PGE1 and placebo group: number of readmissions (2.1 ± 1 vs 1.9 ± 1, P = 0.61), total duration of readmission (27 ± 12 vs 29 ± 12, P = 0.67), survival rate (10.1 ± 3.8 vs 9.6 ± 3.4, P = 0.71), overall survival rate after one year [8 (53.3%) vs 7 (47%), P = 0.72], overall survival rate after two years [3 (20%) vs 3 (20%), P = 0.99], and overall survival rate after three years [0 vs 1 (6.7%), P = 0.99], respectively. CONCLUSION: In conclusion, PGE1 did not shorten or lengthen the survival of patients with esophageal cancer. Larger studies are suggested.

创伤性脊髓损伤急性期前列腺素E1对血管相关因子的调节和微循环功能的保护

背景:前列腺素E1被证明在血管扩张、炎症、白细胞迁移和黏附中发挥调节作用,但其对创伤性脊髓损伤后脊髓微循环的作用尚缺乏深入的研究。目的:探讨在大鼠创伤性脊髓损伤急性期给予前列腺素E1对血管相关因子的调节和微循环功能的保护作用机制。方法:将72只雌性SD大鼠随机分为3组(n=24),即假手术组、脊髓损伤组、前列腺素E1组。后两组用Allen’s打击法建立脊髓损伤的体内模型,前列腺素E1组大鼠在脊髓损伤后15 min内立即尾静脉注射脂质前列腺素E110μg/kg。分别在损伤后2,24 h测定脊髓微循环血流量和血氧饱和度、脊髓微血管直径和面积、脊髓含水量、血管功能调节因子(血浆血管性血友病因子、血栓素A2、前列环素、内皮素1)和炎症因子(肿瘤坏死因子α、白细胞介素1β)的表达。结果与结论:①脊髓损伤后2 h,前列腺素E1组大鼠的脊髓微血管直径及面积、脊髓微循环血流量和血氧饱和度均高于脊髓损伤组(P<0.05),脊髓含水量低于脊髓损伤组(P<0.05),血浆血管性血友病因子、脊髓组织血栓素A2/前列环素及内皮素1质量浓度均低于脊髓损伤组(P<0.05);②脊髓损伤后24 h,前列腺素E1组大鼠的脊髓微血管面积、血流量和血氧饱和度均高于脊髓损伤组(P<0.05),脊髓含水量低于脊髓损伤组(P<0.05),血浆血管性血友病因子、脊髓组织血栓素A2/前列环素及内皮素1、肿瘤坏死因子α、白细胞介素1β的质量浓度均低于脊髓损伤组(P<0.05);③脊髓损伤组大鼠损伤后24 h的脊髓微血管直径及面积、脊髓微循环血流量和血氧饱和度均高于损伤后2 h(P<0.05),血浆血管性血友病因子、脊髓组织血栓素A2/前列环素、肿瘤坏死因子α、白细胞介素1β的质量浓度均高于损伤后2 h(P<0.05),但是脊髓组织内皮素1质量浓度低于损伤后2 h(P<0.05);④前列腺素E1组大鼠损伤后24 h的脊髓微循环血流量和血氧饱和度低于损伤后2 h(P<0.05),脊髓微血管直径及面积、脊髓含水量高于损伤后2 h(P<0.05);⑤以上结果表明,脊髓损伤大鼠伤后即刻静脉给予前列腺素E1,可调节血管功能调节因子、炎症因子并改善脊髓损伤后脊髓微循环,这为寻找治疗急性脊髓损伤的药物提供了潜在的基础。

前列腺素E1联合目标导向液体复苏对脓毒性休克治疗效果及血管内皮功能和组织灌注的影响

目的 探究前列腺素E1联合目标导向液体复苏对脓毒性休克临床效果及血管内皮功能和组织灌注水平的影响。方法 收集2019年1月至2021年12月在本院接受治疗的150例脓毒性休克患者,并应用随机数字表法将其均分为2组。对照组给予早期目标导向液体复苏治疗,观察组给予前列腺素E1与早期目标导向液体复苏的联合治疗。对比2组临床治疗效果、血管内皮功能和组织灌注水平。结果 与对照组比,观察组复苏液[(3 173±632)ml和(3 613±562)ml]和多巴酚丁胺[(53±10)mg和(64±7)mg]用量明显减少,复苏成功时间[(4.4±1.0)h和(4.7±1.1)h]和多巴酚丁胺用时[(5.2±1.6)d和(5.8±1.8)d]缩短,并发急性呼吸窘迫综合征(ARDS)率(1.3%和10.7%)明显下降,差异均具有统计学意义(P<0.05)。观察组复苏后6 h和复苏后48 h的急性生理与慢性健康评分(APACHEⅡ)评分[(17±5)分和(19±3)分、(13±5)分和(16±3)分]、序贯器官衰竭评分(SOFA)评分[(8.7±2.5)分和(9.8±2.8)分、(6.1±2.0)分和(7.4±2.4)分]水平均明显低于对照组,复苏后48 h的血清内皮素-1(ET-1)[(45±14)pg/ml和(50±15)pg/ml]、血栓调节蛋白(sTM)[(3.1±0.9)ng/ml和(3.7±1.1)ng/ml]、E-选择素(E-SLT)[(26±6)ng/ml和(28±6)ng/ml]、动脉血乳酸[(3.2±1.0)mmol/L和(3.6±1.0)mmol/L]、氧摄取量(O_(2)UR [(24±5)mmHg和(26±5)mmHg]均明显低于对照组,动脉血氧饱和度(SCVO_(2))[(81±7)%和(78±8%)]、外周血管阻力指数(SVRI)[(1 955±345)ds×m^(2)/cm^(5))和(1 826±413)ds×m^(2)/cm^(5))]明显高于对照组,差异均具有统计学意义(P<0.05)。结论 前列腺素E1联合目标导向液体复苏能有效减少脓毒性休克患者复苏液总用量,缩短液体复苏时间和血管活性药物使用时间,抑制机体血管内皮损伤,改善机体组织灌注水平和氧代谢状态,改善患者预后。

Cardioprotective effect of liposomal prostaglandin E1 on a porcine model of myocardial infarction reperfusion no-reflow

Objective： To evaluate whether liposomal prostaglandin E1 （lipo-PGE1） can decrease reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction （AMI）. Methods： Twenty-two male Chinese mini-swines were randomized into three groups： six in a sham-operation group, and eight each in the control and lipo-PGE1 groups. The distal part of the left anterior descending coronary artery （LAD） in the latter two groups was completely occluded for 2 h, and then reperfused for 3 h. Lipo-PGE1 （1 pg/kg） was injected 10 min before LAD occlusion until reperfusion for 1 h in the lipo-PGE1 group. Hemodynamic data and proinflammatory cytokines were examined before AMI, 2 h after occlusion, and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography （MCE） and double staining were performed to evaluate the myocardial no-reflow area （NRA）. Results： Left ventricular systolic pressure and end-diastolic pressure significantly improved in the lipo-PGE1 group after reperfusion compared with the control group and also 2 h after AMI （P〈0.05 for both）. MCE and double staining both showed that lipo-PGE1 decreased reperfusion NRA after AMI （P〈0.05, P〈0.01）. Lipo-PGE1 decreased serum interleukin-6 （IL-6） and tumor necrosis factor-a （TNF-a） after myocardial infarction reperfusion （P〈0.05 for both）. Conclusions： Lipo-PGE1 is cardioprotective in our porcine model of myocardial infarction reperfusion no-reflow, decreasing NRA and attenuating the inflammatory response.

血清PGE1、GPX1及子宫动脉超声参数评估凶险性前置胎盘植入导致的产后出血

目的:探讨血清前列腺素E1(PGE1)、谷胱甘肽过氧化物酶1(GPX1)及子宫动脉超声参数与凶险性前置胎盘植入导致产后出血关系。方法:回顾性收集2019年4月-2022年4月本院治疗的凶险性前置胎盘植入产妇98例临床资料为观察组,凶险性前置胎盘不伴植入产妇80例为对照组,分析两组血清PGE1、GPX1及子宫动脉超声参数阻力指数(RI)、搏动指数(PI)、血管最大血流速度(PSV)和收缩/舒张期速度比值(S/D)等,分析观察组不同临床特征、胎盘植入分类、发生和未发生产后出血产妇上述指标差异,受试者工作特征(ROC)分析上述指标预测产后出血价值。结果:观察组血清PGE1(35.54±9.32pg/ml)和GPX1(30.50±9.14U/L)低于对照组(47.49±9.20 pg/ml、38.38±9.40 U/L)。RI(0.37±0.10)、PI(0.46±0.11)低于对照组(0.44±0.12、0.57±0.10),PSV(44.50±8.12cm/s)和S/D(6.80±1.10)高于对照组(36.61±8.05 cm/s、5.82±1.03)(均P<0.05)。观察组不同年龄、分娩孕周和体质指数产妇血清PGE1、GPX1及子宫动脉超声参数比较无差异(P>0.05),粘连型胎盘植入、植入性胎盘植入、穿透性胎盘植入者RI和PI依次降低,PSV和S/D依次升高,发生产后出血产妇血清PGE1、GPX1、RI和PI均低于未发生产后出血产妇(均P<0.05)。PGE1、GPX1、RI和PI与产后出血量呈负相关(P<0.05)。PGE1、GPX1及RI、PI预测凶险性前置胎盘植入产后出血的ROC曲线下面积分别为0.651、0.668、0.623和0.636。结论:血清PGE1、GPX1及子宫动脉超声参数与凶险性前置胎盘植入的胎盘植入程度、产后出血有关,PGE1、GPX1、RI和PI预测产后出血有一定价值。

前列腺素E1治疗肝硬化腹水伴肝肾综合征的效果及对C反应蛋白、NO水平的影响

目的观察前列腺素E1对肝硬化腹水伴肝肾综合征近、远期疗效,分析其作用机制,以期找出阻断肝硬化腹水进展危险因素。方法选取2017年1月至2020年12月德州市中医院收治的肝硬化腹水伴肝肾综合征患者80例,按照随机数表法将患者分为治疗组(n=40)与对照组(n=40),对照组给予常规治疗,治疗组另加前列地尔注射液20 g+0.9%NS 100 ml静脉滴注,1次/d,4周为1个疗程。观察两组治疗后4周腹水量(B超测腹水深度)及24 h尿量、肝肾功能、肾血流及外周血C反应蛋白(CRP)、一氧化氮(NO)水平变化;随访3个月观察腹水复发率及病死率情况。结果4周后治疗组腹水量少于对照组,24 h尿量多于对照组;谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)、尿素氮(BUN)、肌酐(Cr)、尿微量白蛋白指标低于对照组,白蛋白(ALB)、凝血酶原活动度(PTA)、肾血流量高于对照组;CRP、NO水平低于对照组,差异均有统计学意义(P<0.05)。随访3个月治疗组腹水复发率及病死率低于对照组,差异有统计学意义(P<0.05)。结论前列腺素E1有改善肝肾功能、增加肾血流、减轻机体炎症反应等作用,可促进腹水消退、降低病死率,对肝硬化腹水伴肝肾综合征近、远期效果良好。

前列腺素E1对原发性肾病综合征作用初探(英文)

Objective:To investigate the effect of prostaglandin E1 (PGE1) (Alprostadii injection) on patients with primary nephrotic syndrome(PNS). Methods: 37 patients with PNS were recruited to study the effect of prostaglandin E1 on platelet aggregation function [ PAG (5,) PAG( m ) ], serum total protein (TP) , albumin (Al),blood urea nitrogen(BUN) ,serum creatinine(Scr) ,cholesterol(CHO), triglyceride(TG), protein in 24-hour urine (Pr/24h) and platelet account (PLT). Results: TP, Al, CHO, TG, BUN, Scr, Pr/24h, PAG(5) and PAG(m) in PNS group before treatment were significantly different from those in control group(P＜0.05, P＜0.01) while no significant difference was found for PLT. When treated with PGE1 , TP,Al,CHO, TG, Pr/24h, ADP- induced PAG(5) ,and Adr- induced PAG(5) and PAG(m) were significantly different from those before treatment (P＜0.05). Adr- induced PAG(5) and PAG(m) were significantly different. Adr- induced PAG(5) was xsitively correlated with BUN and Scr in PNS(P＜0.01). Similar correlation was found between ADP-induced PAG(5) and Al ,BUN,Scr,Pr/24h(P＜0.05), AD- induced PAG(m) and TP,CHO(P＜0.05). Conclusions: PGE1 may be an effective drug for the treatment for hypercoagulation in patients with PNS.

生长抑素与前列腺素E1联合应用治疗重症急性胰腺炎初步临床研究

目的观察生长抑素(SS)和前列腺素E1(PGE1)联合应用对重症急性胰腺炎(SAP)的临床效果,探讨两者联合应用的作用机制。方法将收治的31例SAP的患者分为对照组(SS治疗组,n=15)和联合治疗组(SS+PGE1组,n=16),于入院后第1、4、7天检测外周血内毒素、肿瘤坏死因子-α(TNF-α)、IL-6、IL-10及CRP的变化;监测血小板(PLT)、凝血酶凝结时间(TT)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)和D-二聚体;检测血清淀粉酶和乳酸脱氢酶和清蛋白;观察ICU入住时间、治疗14d后APACHEⅡ评分、Binder积分、中转手术率、28d病死率。结果与对照组比较,联合治疗组于治疗7、14d后上述临床及实验室检测指标均有改善,差异有统计学意义(P<0.05)。结论 SS和PGE1联合应用可显著改善SAP患者的预后,缩短ICU入住时间,降低28d病死率,其可能的作用机制是减轻急性期炎症介质和细胞因子的过度释放,提高机体免疫能力等多层次,改善胰腺的微循环,纠正高凝状态,避免SAP患者并发多器官功能障碍。

前列腺素E1治疗糖尿病肾病1年的随访研究

目的观察前列腺素E1(PGEl)治疗不同时期糖尿病肾病(DN)随访1年的疗效。方法糖尿病肾病患者根据Mogensen DN诊断标准分为Ⅲ、Ⅳ、Ⅴ期。其中Ⅳ期患者根据尿蛋白水平分为Ⅳ早期(尿蛋白<1.5g/d)、Ⅳ中期(1.5g/d<尿蛋白<2.5g/d)和Ⅳ晚期(尿蛋白>2.5g/d)。各期患者再随机给予4种治疗方案:PGE1组、PGEl+血管紧张素转换酶抑制剂(ACEI)组、ACEI组和空白对照组。测定各组治疗前及治疗后15d、1年的24h尿蛋白和24h尿微量白蛋白水平。结果(1)Ⅲ期及Ⅳ早期患者:PGE1+ACEI组和PGE1组治疗后15d及1年时尿蛋白及尿微量白蛋白均较治疗前明显下降(P<0.01),PGE1+ACEI组下降幅度始终大于ACEI组(P<0.01或P<0.05)。(2)Ⅳ中期及Ⅳ晚期患者:PGE1+ACEI组治疗后15d及1年时尿蛋白及尿微量白蛋白均较治疗前明显下降(P<0.01),下降幅度始终大于ACEI组(P<0.01)。PGE1组治疗后15d时,两指标水平较治疗前明显下降(P<0.01),但治疗后1年时两指标下降幅度减小且水平高于ACEI组(P<0.05)。(3)Ⅴ期患者:PGE1+ACEI组和PGE1组治疗后15d时尿蛋白及尿微量白蛋白均较治疗前明显下降(P<0.01),下降幅度大于ACEI组(P<0.01)。治疗后1年时,PGE1+ACEI组的两指标水平与治疗前无统计学差异,但仍低于ACEI组;PGE1组及ACEI组的两指标水平较治疗前升高(P<0.05),两组之间无统计学差异。结论PGE1对早期糖尿病肾病治疗效果优于晚期。PGE1与ACEI联合应用疗效最好,随访1年时疗效仍好于单用前列腺素E1及ACEI。

前列腺素E1对高血压脑出血患者血肿周围组织血流量及预后的影响

目的观察前列腺素(PG)E1对高血压脑出血患者血肿周围组织血流量及预后的影响。方法 40例高血压脑出血患者随机分为PGE1组和对照组,两组患者均给予脑出血的常规治疗;PGE1组发病后第5d起给予PGE1治疗15 d。发病后第5 d、20 d进行单光子发射计算机断层扫描脑灌注显像,应用半定量分析法计算血肿区及血肿周围组织近区、远区及额顶叶区的局部脑血流量(rCBF);发病第1 d、第5 d、第12 d和第20 d进行头颅CT检查,观察两组患者血肿及血肿周围低密度区体积;同时应用美国国立卫生研究院卒中量表(NIHSS)进行神经功能缺损程度评分;发病第1 d、第20 d进行改良的Rank in量表(mRS)评分,第90 d时再次分别进行NIHSS和mRS评分。结果发病第20 d PGE1组血肿周围近区及远区rCBF较治疗前及对照组明显升高(均P<0.01);发病第12 d、20 d时血肿体积以及发病第20 d时血肿周围低密度区较对照组明显缩小(均P<0.01);发病第20 d和第90 d时NIHSS评分较对照组明显降低(均P<0.05);发病第90 d时mRS评分较对照组明显降低(P<0.01)。结论高血压脑出血患者应用PGE1治疗,可增加血肿周围rCBF,促进神经功能缺损的恢复,改善预后。

前列腺素E1在体外循环中调控炎症反应及肺保护作用的研究

目的:研究前列腺素E1(PGE1)调控炎症系统对体外循环(CPB)中肺损伤的保护作用。方法:选取2006年3月至6月24例风湿性心脏瓣膜病手术患者,随机分为对照组和实验组(PGE1治疗组),各12例。实验组于麻醉诱导时从中心静脉泵入PGE1[15ng/(kg·min)]至CPB结束。于转流前5 min、心脏复跳后15 min检测左、右心房血中性粒细胞(PMN)及血小板(Plt)计数。检测转流前5 min(T1)、转流30 min(T2)、心脏复跳后15 min(T3)、CPB结束1h(T4)和6 h(T5)的血清sE-选择素、C反应蛋白(CRP)浓度。记录麻醉诱导后、开胸后、CPB及手术结束时的肺顺应性(CL)及氧合指数(OI)。结果:①两组转流前左、右心房血PMN、Plt无显著差异。心脏复跳后15 min对照组左心房血PMN、Plt明显低于右心房血(P<0.01),实验组左、右心房血PMN、Plt计数无显著差异(P>0.05);②CPB开始后两组sE-选择素的浓度逐渐升高,对照组更为明显(P<0.01);③CPB开始后实验组CRP浓度较对照组明显降低(P<0.01);④CPB结束时,实验组氧合指数(oxygenation index,OI)显著低于对照组(P<0.01),肺顺应性(compliance of lung,CL)显著高于对照组(P<0.01)。结论:PGE1可减轻CPB引起的PNM及Plt在肺内聚集、抑制血管内皮细胞的激活,减轻血管内皮细胞损伤,减少全身炎症反应,并减轻由此引起的肺损伤。

前列腺素E1脂微球制剂治疗老年糖尿病肾病临床观察

目的 :观察前列腺素E1脂微球载体制剂对老年糖尿病肾病的疗效及不良反应。方法 :5 8例老年糖尿病肾病住院病人 ,男 39例 ,女 19例 ,平均年龄(6 8.2± 5 .7)岁 ,给予PGE110 μg ,qd ,连续应用 14d。结果 :治疗后早期糖尿病肾病 2 4h尿白蛋白排泄率和临床糖尿病肾病 2 4h尿蛋白定量较治疗前相比明显降低 ,而 2 4h肌肝清除率较治疗前明显升高。结论 :PGE1可以改善肾血流量 ,降低尿蛋白排泄量 ,在老年糖尿病肾病的应用上具有广阔前景。

前列腺素E1对脑梗死后神经干细胞增殖和迁移的影响

目的观察前列腺素E1对右侧大脑中动脉皮层支闭塞(middle cerebral artery occlusion,MCAO)大鼠内源性神经干细胞增殖和迁移的影响。方法36只大鼠随机分为前列腺素E1(10μg.kg-1·d-1)组,溶剂对照组和假手术组,每组12只。3组大鼠均腹腔注射5-溴脱氧尿嘧啶核苷(5-bromo-2'-deoxyuridine,BrdU)以标记脑内新增殖细胞,并于MCAO术后7d、14d行神经功能评分后处死,测脑梗死体积,观察梗死同侧侧脑室室管膜下区(subventricular zone,SVZ)BrdU+细胞、BrdU+/doublecortin(DCX)+细胞表达、梗死灶周BrdU+细胞表达及SVZ区BrdU+/DCX+细胞的迁移距离。结果MCAO术后7d、14d,与溶剂对照组及假手术组相比,前列腺素E1治疗增加了梗死侧SVZ区BrdU+细胞(7 d:380.3±14.3 vs.251.3±9.5 vs.50.3±5.4;14 d:230.2±10.1 vs.126.2±8.8 vs.24.3±6.3,P<0.05)、BrdU+/DCX+细胞(7 d:209.0±19.6 vs.109.8±14.4 vs.27.3±5.9;14 d:96.2±13.0 vs.47.3±6.8 vs.25.7±6.2,P<0.05)和梗死灶周皮质BrdU+细胞(7 d:349.7±9.2 vs.203.5±12.2 vs.53.8±8.4;14 d:203.4±13.3 vs.136.7±11.8vs.27.2±6.2,P<0.05)表达;术后7 d,前列腺素E1组梗死侧SVZ区BrdU+/DCX+细胞迁移距离比溶剂对照组更远(6039.3μm±1035.6μm vs.3591.5μm±716.6μm,P<0.05);前列腺素E1组与溶剂对照组比较,脑梗死后神经功能评分改善[7 d:1.5(1.0,2.0)vs.2.0(2.0,3.0);14 d:0.5(0,1.0)vs.1.0(1.0,2.0),P<0.05]。结论前列腺素E1可促进大鼠脑梗死后梗死侧SVZ区内源性神经干细胞增殖、迁移和神经功能康复。

西洛他唑和前列腺素E1联合治疗对糖尿病肾病初期内皮素和一氧化氮的影响

目的探讨西洛他唑和前列腺素E1联合治疗对糖尿病肾病初期内皮素(ET)和一氧化氮(NO)的影响。方法检测患者的一般临床指标及西洛他唑和前列腺素E1干预治疗1个月NO、ET、尿白蛋白排泄率(UAER)的变化。结果 UAER和ET:正常蛋白尿(NA)组、微量蛋白尿(MA)组逐渐升高,NO逐渐降低。MA组中UAER、ET和NO:西洛他唑组(B组)干预治疗后较治疗前升高,二者比较差异有统计学意义(P<0.05);前列腺素E1组(C组)治疗后较治疗前升高更明显,二者比较差异有统计学意义(P<0.01);联合治疗组(D组)治疗后较治疗前升高更显著,二者前后比较差异有统计学意义(P<0.01)。ET与UAER呈强正相关(rET=0.458,P<0.01);NO与UAER呈强负相关(rNO=-0.493,P<0.01)。结论西洛他唑和前列腺素E1治疗糖尿病肾病的疗效较肯定,并且联合治疗效果好于单药治疗。

脂质体携载前列腺素E1对冠脉介入治疗后炎症因子的影响

目的:观察早期使用脂质载体前列腺素E1对经皮冠状动脉介入治疗(Percutaneous coronary intervention,PCI)患者血浆炎症因子的影响。方法:74例行PCI治疗的患者随机分成实验组和对照组。前者入选后给予PGE120μg+生理盐水40ml静脉注射,Bid×3d,对照组患者则不给。其余基础治疗措施相同。于PCI术前1d、术后2d、术后5d、术后4周查CRP、IL-6、TNF-α,并观察观察术后60d内早期心脏事件发生情况。结果:两组患者经PCI治疗后1d,CRP水平有所上升,与同组术前1d相比有显著差异(P<0.05),但与对照组相比均未见有差异(P>0.05)。术后5d～4周,实验组的水平已较术前有所下降(P<0.05),对照组较术前亦有下降(P<0.05),并且实验组CRP的水平较对照组下降更为明显(P>0.05)。炎症因子IL-6、TNF-α和CRP表现出一样的变化趋势。并且,用药期间2组未出现不良反应,安全性良好。结论:在PCI术后早期CRP、IL-6和TNF-α可有升高,但早期应用Lipo-PGE1后,可有效抑制炎症因子水平。

小剂量前列腺素E1乳膏治疗勃起功能障碍的疗效观察

目的 :探讨小剂量前列腺素E1(PGE1)乳膏尿道口给药治疗勃起功能障碍 (ED)的疗效。 方法 :按入选标准及国际勃起功能问卷 (IIEF) 5评分录取 4 3例ED病人 ,经签知情同意书后 ,进入为期 4周的开放性临床研究。采用尿道口内挤入乳膏的方法 ,以手持阴茎保持向上位以手指关闭尿道口 30s ,每次尿道口给药量为 30 0mcgPGE1(75mg乳膏 ) ,每例最少用药 2次以上。 结果 :对主要疗效指标 (IIEFQ3+Q4 )的分析结果显示 ,受试者在使用本研究药物后进行性活动时 ,其阴茎勃起程度达到显效和有效者占 70 .73%。若按性交次数计算 ,性交成功率达 86 .4 1%。总体疗效评估的分析结果为 73.17%。同时 ,所有次要疗效评估 (IIEFQ1、Q2、Q5～Q15 )的分析结果 ,均一致支持主要疗效评估的分析结果。因各种原因中止试验的有 2例 ,发生尿道疼痛或阴茎红肿共 6例 ,占14 .6 3% ,多数为轻度、一过性的。 结论 :可将乳膏的PGE1给药剂量降至 30 0mcg时 ,采用尿道口挤入方法给药 。