体外循环心脏瓣膜置换术患者血浆H2S浓度变化及与肺损伤关系的探讨

目的：观察体外循环心脏瓣膜手术患者血浆硫化氢（H2S）浓度的改变,并探讨（H2S）与肺损伤的关系。方法选择30例接受心脏瓣膜置换术的患者,分别于CPB开始前、结束时、手术结束后1h、6h、12h抽取动脉血,测定血浆H2S浓度,并测定动脉血气分析,计算呼吸指数（RI）及氧合指数（OI）。结果在手术结束后1h及结束后6h血浆H2S浓度与CPB开始前（基础值）及CPB结束时相比差异有统计学意义（P〈0.01）,其中在手术结束后1h血浆H2S浓度达到最高峰值,之后呈下降趋势,12h后接近基础值;血浆H2S浓度与RI数呈高度正相关（r=0.49,P=0.006）,与OI呈高度负相关（r=0.54, P=0.002）。结论体外循环可引起H2S浓度增高,且与肺损伤相关。     

体外循环下心脏直视手术的体温变化及护理

目的探讨体外循环下心脏直视手术期体温的变化及护理。方法对54例体外循环下心脏直视手术期病人的鼻咽温、肛温进行了监测,分别于皮肤消毒前、体外循环(CPB)开始、CPB中维持、CPB停止、关胸、手术结束贴敷料时等6个点测量鼻咽温、肛温,观察体温变化,同时记录室温、湿度,并于CPB停止至手术结束这段时间应用综合性体温保护技术,以维持病人体温。结果54例CPB下心脏手术期平均室温为(23.7±1.1)℃,平均湿度为(58.6±3.4)%,手术结束时平均鼻咽温为(36.1±0.8)℃,手术结束时平均肛温为(36.5±0.5)℃。经统计学分析,鼻咽温:CPB开始、CPB中维持与皮肤消毒前相比,P<0.01;CPB停止、关胸、手术结束贴敷料与皮肤消毒前相比,P>0.05。肛温:CPB开始、CPB中维持、CPB停止、关胸、手术结束贴敷料等几个点测定的数据与皮肤消毒前相比,经统计学分析,P<0.01。结论在体外循环下心脏直视手术期,应采取综合性体温保护技术,努力维持病人体温,避免因各种因素引起病人低温,以保证手术结束时,病人的体温在正常范围内。     

基质金属蛋白酶-2/9及其组织抑制剂比例失衡在高氧所致急性肺损伤中的作用

目的 探讨基质金属蛋白酶-2/9(MMP-2/9)及其组织抑制剂(TIMP-1/2)在高氧所致急性肺损伤(ALI)发病过程中的作用.方法 将54只小鼠置于含体积分数大于98%氧气的密闭室中,以18只呼吸正常空气的小鼠作为对照组.分别于暴露24、48和72 h活杀各组小鼠,取肺组织标本,测定肺湿/干重(W/D)比值、支气管肺泡灌洗液(BALF)中蛋白含量及胸腔积液,以评价肺损伤程度.用逆转录-聚合酶链反应(RT-PCR)测定肺组织MMP-2/9和TIMP-1/2的mRNA表达;用酶联免疫吸附法(ELISA)测定BALF中MMP-2/9及TIMP1/2的蛋白含量.结果 高氧能引起ALI,各实验组的肺W/D比值、BALF中蛋白浓度及胸腔积液均明显高于对照组(P<0.05或P<0.01).RT-PCR结果显示,高氧组肺组织MMP-2/9及TIMP-1的mRNA表达均较对照组明显增高(P<0.05或P<0.01),TIMP-2 mRNA表达无明显变化;MMP-2/TIMP-2的mRNA比值在高氧组中均明显升高(P均<0.01).ELISA结果显示,高氧组BALF中MMP-2/9和TIMP-1蛋白含量较对照组明显升高(P<0.05或P<0.01),而TIMP-2蛋白含量同样无明显变化;MMP-2/TIMP-2的蛋白比值在高氧组中也明显升高(P均<0.01).结论 高氧能引起ALI伴MMP-2/9和TIMP-1的表达增高,而MMP-2/TIMP-2平衡失调导致细胞外基质降解在其发生过程中起重要作用.     

不同剂量乌司他丁对体外循环患者炎症反应及呼吸功能的影响

目的 研究不同剂量乌司他丁在体外循环(CPB)心脏直视手术中对肺损伤的保护作用机制.方法 采用前瞻性随机对照研究方法,选择42例心脏瓣膜置换术患者,随机分为对照组、乌司他丁8 kU/kg组(U1组)及乌司他丁12 kU/kg组(U2组),3组分别于麻醉诱导后术前(T1)及停止CPB 1 h(T2)、4 h(T3)、24 h(T4)取静脉血,检测血浆肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、IL-10的浓度;同时测定动脉血气,对比观察氧合指数(PaO_2/FiO_2)及呼吸指数(RI).结果 ①3组患者T1时血浆TNF-α、IL-6和IL-10比较差异均无统计学意义(P均>0.05),T2～4时则均显著升高(P<0.05或P<0.01).与对照组比较,U1、U2组T2～4时血浆TNF-α、IL-6浓度降低,IL-10浓度升高,且U2组变化较U1组明显(P<0.05或P<0.01).②3组患者T1时PaO_2/FiO_2、RI比较差异均无统计学意义(P均>0.05),T2～4时则出现PaO_2/FiO_2减少、RI值增大(P<0.05或P<0.01).与对照组比较,U1、U2组T2～4时PaO_2/FiO_2增大、RI值减小,且U2组变化较U1组更为显著(P<0.05或P<0.01).结论 在CPB过程中,乌司他丁能明显抑制促炎因子TNF-α、IL-6的产生,上调抗炎因子IL-10的释放,减轻肺损伤,改善CPB术后肺功能,并呈剂量-效应关系.     

1，6－二磷酸果糖对婴幼儿肺缺血再灌注损伤的保护作用

目的:探讨1,6-二磷酸果糖(huetose-1,6-diphosphatin,FDP)在体外循环中对中重度肺动脉高压婴幼儿的肺保护作用.方法:将24例先天性心脏病伴中重度肺动脉高压婴幼儿随机分为FDP组(F组,12例)和对照组(D组,12例).F组体外循环前静脉给FDP 200mg/kg.分别在体外循环前后各时间点测定两组血液中一氧化氮(N0)、内皮素-1(ET-1)、基质金属蛋白酶-9(MMP-9)浓度,在光镜及电镜下观察两组体外循环前后肺组织结构变化.结果:体外循环前两组指标无统计学差异(P>0.05),体外循环后血清NO浓度均较体外循环前降低(P<0.05),血浆ET-1、MMP-9浓度均较体外循环前升高(p<0.05).F组中NO浓度高于D组(P<0.05),ET-1、MMP-9浓度较D组低(P<0.05).两组在体外循环后肺结构和肺血管内皮细胞较体外循环前均有损害,F组肺组织结构破坏及血管内皮细胞损害较D组轻.结论:FDP在体外循环中对中重度肺动脉高压婴幼儿的肺组织和血管内皮细胞具有保护作用.     

体外循环急性肺损伤与基质金属蛋白酶-9相关性研究

目的　探讨基质金属蛋白酶 9(MMP 9)在围体外循环术 (CPB)中的变化及其与急性肺损伤的相关性。方法　临床选择 2 0例接受CPB的患者 ,分别测定CPB开始、开始后 5min、结束时、结束后 1h和结束后 6h血浆MMP 9和TNF α浓度 ,同时测定CPB结束后各时间点的A aDO2 、呼吸指数 ,记录主动脉阻断时间、转流时间及拔管时间 ,分析血浆MMP 9和TNF α在围CPB期间的变化以及与影响因素和肺功能之间的相关性。结果　①血浆MMP 9和TNF α的浓度在CPB结束时达到最高峰值 ,之后呈下降趋势 ;②血浆MMP 9的升高与TNF α升高呈正相关 ,CPB结束时血浆MMP 9浓度与主动脉阻断时间最有相关性 ;③CPB结束后A aDO2 的变化与术后血浆MMP 9浓度的变化有相关性 ,而RI变化与MMP 9之间未见有相关性。结论　CPB可以引起血浆MMP 9和TNF α浓度的明显增高 ,其中主动脉阻断时间对CPB结束时血浆MMP 9的影响最为明显。CPB过程中MMP 9与TNF α之间存在着相关性 ,MMP 9浓度与CPB结束后A aDO2 的变化有相关性     

体外循环手术期间精氨酸对红细胞作用的研究

目的 探讨体外循环(CPB)手术期间L-精氨酸对患者红细胞的影响.方法 择期在CPB下行瓣膜置换的风湿性心脏病患者30例,随机分为L-精氨酸组(L组)和对照组(C组),每组15例.于麻醉后切皮前,L组L-精氨酸按200 mg/kg的剂量加入5%葡萄糖注射液50 ml中,经颈内静脉用注射泵以99 ml/h的速度泵人体内.C组用等量5%葡萄糖注射液,用法同L组.分别于麻醉诱导后切皮前(基线值T1)、转流30 min(T2)、转流结束时(T3)、手术结束时(T4)、术后24 h(T5)五个不同时段分别抽取静脉血,测定血中游离血红蛋白(FHb)、丙二醛(MDA)、红细胞C3b受体花环率(RBC-C3bRR)、红细胞免疫复合物花环率(RBC-ICR).结果 (1)MDA、FHb、RBC-ICR:转机前,L、C组间无差异,两组转机30 min后的各标本含量均明显高于转机前(P<0.01),于CPB结束时各含量开始下降,转机30 min后L组含量又明显低于C组,组间差异有统计学意义(P<0.01).(2)RBC-C3bRR:转机前两组RBC-C3bRR无明显差异,转机30 min后两组RBC-C3bRR均明显低于转机前(P<0.01),于CPB结束时各含量开始回升,但转机30 min后L组RBC-C3bRR又明显高于C组,组间差异有统计学意义(P<0.01).结论 心内直视手术时CPB可导致红细胞损伤及其免疫功能下降.围手术期应用精氨酸对CPB中RBC及其免疫功能有较好的保护作用,并可促进CPB术后患者红细胞免疫功能的恢复.     

小潮气量通气对肺损伤兔外周血中TNF-α、IL-6、IL-8、MMP-9表达的影响

目的小潮气量机械通气对内毒素性急性肺损伤(ALI)动物模型外周血中TNF-α、IL-6、IL-8、MMP-9表达的影响。方法健康新西兰白兔24只,平均体重(2.48±0.30)kg,随机分为3组:(1)急性肺损伤小潮气量机械通气组(ALI+LV组):通过气道内滴入脂多糖(LPS)(2.5 mg/kg)制作急性肺损伤动物模型,然后在小潮气量机械通气持续24 h(容量控制VT:6 ml/kg;f:40/min;Fi O2:0.6;I∶E 1∶1.5;PEEP 5 cm H2O)。(2)急性肺损伤组(LPS组):气道内滴入LPS。(3)正常对照组(C组):气道内注入与LPS相同剂量的生理盐水。实验期间于0 min,30 min,1 h,2 h,4 h,6 h,8 h,12 h,24 h各抽取动脉血1 ml,测动脉血氧分压(Pa O2),静脉血2 ml,用ELISA技术检测血浆TNF-α、IL-6、IL-8、MMP-9表达情况。实验开始24 h后处死动物,取左肺测湿/干(W/D)重比。结果 (1)ALI组较对照组外周血中TNF-α、IL-6、IL-8、MMP-9表达明显升高,并且随时间延长逐渐增加。(2)LV+ALI组与ALI组比较,外周血中TNF-α、IL-6、IL-8、MMP-9在6 h之前差异无显著性,在6 h后显著减低,且随时间延长,降低的幅度越大,效果越明显。(3)气道滴入LPS后,ALI组较对照组Pa O2显著减低(P<0.05),低氧血症逐渐加重。经小潮气量通气后,LV+ALI组较ALI组6 h后低氧血症明显改善,W/D值明显下降(P<0.05)。结论小潮气量机械通气不能改善炎症性肺损伤早期外周血中炎症因子水平,但可以明显减低晚期炎症性肺损伤外周血中炎症因子,可能和小潮气量改善晚期肺泡通气有关。     

血浆S100A12与婴幼儿体外循环术后非感染性肺部并发症的相关性研究

目的 动态观察婴幼儿体外循环(CPB)围术期血浆中S100A12和可溶性晚期糖基化终末产物受体(sRAGE)水平变化,探讨其在婴幼儿CPB术后非感染性肺部并发症(NPC)早期预测中的作用.方法 采用病例对照研究.选取2011年6月1日至7月31日,在浙江大学附属儿童医院行CPB下心内直视矫治术、年龄＜3岁的先天性心脏病患儿.排除术前肺部有炎症性疾病和肝肾功能异常的患儿.根据术后是否出现胸腔积液、乳糜胸、部分肺不张、肺动脉高压危象、气道紊乱、气胸、纵膈积气、膈神经麻痹,20例被分为NPC组,40例被分为no-NPC组.于手术前,CPB前,CPB后,手术后1、12和24 h,采用ELISA法检测血浆中S100A12和sRAGE浓度.两组之间的浓度差异采用t检验;多因素Logistic回归分析检验S100A12和sRAGE在术后NPC早期预测中的作用,并以优势比(OR)及95％可信区间(95％ CI)表示相对危险度;以P＜0.05为差异具有统计学意义.结果 血浆中S100A12和sRAGE浓度在CPB后立刻明显升高(P＜0.01).术后24h后血浆中sRAGE水平明显低于术前水(P＜0.05),而S100A12仍明显高于术前水平(P＜0.01).CPB术后即刻,NPC组血浆中S100A12和sRAGE水平明显高于no-NPC组(P＜0.05).术后24 hNPC组血浆中S100A12水平仍明显高于no-NPC组(P＜0.05),而两组患儿血浆中sRAGE水平无明显差异(P＞0.05).逐步法Logistic回归分析,CPB后即刻血浆中S100A12水平与术后NPC的发生明显相关(OR=1.042,95％ CI:1.010～ 1.076,P=0.011).CPB后即刻血浆中S100A12与术后机械通气时间(r=0.47,P＜0.01)、住ICU时间(r=0.363,P=0.008)和住院时间(r =0.402,P=0.002)明显相关.结论 婴幼儿CPB术后血浆中S100A12和sRAGE水平立刻明显升高.血浆中S100A12是婴幼儿CPB术后NPC发生和预后的早期预测指标.     

基质金属蛋白酶-9及其抑制剂在糖皮质激素治疗重度慢性阻塞性肺疾病急性加重期的变化及意义

目的 探讨基质金属蛋白酶-9(MMP-9)及其抑制剂1(TIMP-1)在耱皮质激素(简称激素)治疗重度慢性阻塞性肺疾病急性加重期(AECOPD)的变化及意义.方法 以双抗体夹心ELISA法检测AECO.PD患者激素治疗组(41例)和对照组(40例)治疗前后血清MMP-9和TIMP-1水平,并分析与肺功能的关系.结果 ①AECOPD激素治疗组血清MMP-9、TIMP-1浓度、MMP-9/TIMP-1比值[分别为(189.25±52.38)μg/L,(198.38±43.45)μg/L,0.92±0.37]明显低于治疗前[(246.10±68.64)μg/L,(217.63±62.34)μg/L,1.09±0.23],差异均有统计学意义(P<0.01,P<0.05,P<0.05);对照组治疗后MMP-9、TIMP-1、MMP-9/TIMP-1下降,但治疗前、后比较差异无统计学意义(P均>0.05).②激素治疗组治疗后1秒钟用力呼气容积(FEV_1)、FEV_1占正常预计值百分比[(0.83±0.35)L,(46±17)%]比治疗前[(0.72±0.48)L,(34±15)%]有明显改善(P均<0.05).结论 糖皮质激素治疗后患者MMP-9、TIMP-1、MMP-9/TIMP-1下降,FEV.%占正常预计值有明显改善;协调MMP-9/TIMP-1比例失衡,可能是糖皮质激素治疗重度AECOPD机制之一.     

A rise of MMP-2 and MMP-9 in bronchoalveolar lavage fluid is associated with acute lung injury after cardiopulmonary bypass in a swine model

Postoperative acute lung injury (ALI) contributes to the morbidity and mortality following cardiopulmonary bypass (CPB). To determine whether the presence of matrix metalloproteinases (MMPs) is associated with ALI after CPB, MMP-2 and MMP-9 activities in bronchoalveolar lavage fluid (BALF) were compared with parameters indicating impaired gas exchange. In a prospective study, 17 minipigs were subjected to CPB for 60 min. Before and at five and 180 min after CPB, MMP-2 and MMP-9 were assayed in BALF and the arterial-alveolar gradient of oxygen tension (AaDO2), the pulmonary capillary wedge pressure (PCWP) and the water content of lung tissue samples (Wt) were evaluated and compared with baseline values. MMP-2 and MMP-9 increased significantly 5 minutes (2.1- and 6.2-fold, respectively) and 180 minutes (3.4- and 14.3-fold, respectively) post-CPB. AaDO2 and Wt, but not PCWP, increased significantly 180 minutes after CPB and only AaDO2, but not PCWP or Wt, was significantly correlated with MMP-2 (r = 0.66, p = 0.006) and MMP-9 (r = 0.62, p = 0.01). In conclusion, high levels of MMP-2 and MMP-9 in the pulmonary compartment are associated with ALI after CPB.     

Serum levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-1 in human herpesvirus-6–infected infants with or without febrile seizures

Human herpesvirus-6 (HHV-6) is a cause of exanthema subitum and, sometimes, of febrile seizures. However, the pathogenesis of febrile seizures associated with HHV-6 infection remains unclear. We investigated serum matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in infants with HHV-6 infection. Serum levels of both MMP-9 and TIMP-1 were significantly higher in infants with HHV-6 infection than in controls. Serum TIMP-1 levels were significantly higher in infants with febrile seizures than in infants without febrile seizures. Serum MMP-9/TIMP-1 ratios were significantly lower in infants with febrile seizures than in infants without febrile seizures. In infants with HHV-6 infection, positive correlations were found between serum MMP-9 concentrations and the white blood cells (WBC) count, and between serum TIMP-1 concentrations and the WBC count. Positive correlations were also found between the amounts of HHV-6 DNA and the ratios of MMP-9/TIMP-1 in infants with HHV-6 infection. In conclusion, we suggest that high serum levels of MMP-9 and TIMP-1 in infants with HHV-6 infection may induce dysfunction of the blood–brain barrier, eventually causing febrile seizures.     

川崎病患儿血清MMP-9和TIMP-1的水平测定

目的了解血清MMP-9和TIMP-1在川崎病(KD)患儿中的水平及临床意义。方法采用ELISA双抗夹心法测定血清MMP-9和TIMP-1水平;采用终点散射比浊法,利用德灵BNProSpec特种蛋白分析仪检测血清超敏CRP(hs-CRP)水平。结果30例KD患儿大剂量丙种球蛋白静脉滴注前(静丙前)MMP-9水平与静脉滴注后(静丙后)和对照组比较均有显著性差异(P<0.01),静丙后与对照组差别无意义;静丙前和静丙后血清TIMP-1水平和对照组比较均有显著差异(P<0.01),但是静丙前和静丙后差别无意义;KD患儿血清MMP-9和TIMP-1水平与hs-CRP水平无相关性。结论血清MMP-9和TIMP-1参与了KD血管炎的发病机制。     

Predicting survival infants ventilated with high-frequency oscillation

This retrospective study identifies factors which may predict outcome in preterm infants and infants born at term, ventilated with high-frequency oscillation (HFO). In a 16-bed neonatal and paediatric intensive care unit (level III), 58 consecutive preterm and term infants with a median gestational age of 30 (24-41) weeks and a median birth weight of 1200 (520-3660) g suffered respiratory failure and were managed with HFO as rescue therapy. Forty-nine patients (84%) received exogenous surfactant before HFO which was initiated after a median interval of 20 (1-910) hours following birth. The overall survival rate was 70%. No significant differences existed between survivors and nonsurvivors in respect to demographic data. A greater proportion of patients with respiratory distress syndrome survived (76%) than with lung hypoplasia (20%) or with air-leak syndromes (pulmonary interstitial emphysema 60%, pneumothorax 28%). In survivors, the mean oxygenation index (OI) before HFO was significantly lower than that in nonsurvivors (16 +/- 1.3 vs. 26 +/- 3, p < 0.01) and showed a significant reduction of 32% within 4 hours. In contrast, mean OI increased to 68% over the first 4 hours in nonsurvivors and the difference between survivors and nonsurvivors remained significant during this time (after 2 hours: 15 +/- 1.5 vs. 30 +/- 6, p < 0.01; after 4 hours: 11 +/- 1 vs. 43 +/- 1, p < 0.01). A receiver of operator analysis revealed that an initial OI < 25 or alveolar-arterial oxygen difference (AaDO2) < 450 mmHg predicted survival with a sensitivity of 93% and a specificity of 41%. The positive predictive value was 79%; the negative predictive value, 70%. CONCLUSION: A low OI and AaDO2 at the beginning of HFO, improvement in oxygenation over the first four hours of HFO ventilation and no development of air-leak syndromes were associated with a high predicted survival. This allows early identification of infants who may not survive and may benefit from established and alternative modes of respiratory support such as extracorporeal membrane oxygenation, nitric oxide and liquid ventilation.     

Effect of tissue inhibitor of metalloproteinases-l siRNA on endothelial cells injury induced by septic serum北大核心CSCD

Objective: To investigate the effect and possible mechanism of tissue inhibitor of Metalloproteinases-l (TIMP-1) siRNA on human umbilical vein endothelial cells injury induced by serum of septic patient. Methods: Serum samples were separately collected from septic patients and healthy controls. Human umbilical vein endothelial cells (HUVECs) were randomly divided into blank group (normal culture cells), control group (culture medium with 10% control serum), septic group (culture medium with 10% septic serum), negative control group (negative siRNA + 10% septic serum), and TIMP-1 siRNA group (TIMP-1 siRNA + 10% septic serum). The survival rate of endothelial cells was detected by MTT assay. The levels of matrix Metalloproteinase-9 (MMP-9) and TIMP-1 in supernatant of culture medium were measured by enzyme-linked immunosorbent assay (ELISA). The levels of MMP-9, TIMP-1 and Thrombomoduline (TM) in endothelial cells were examined by Western blot. Results: Compared with control group, the cell survival rate of septic group decreased 12 hours after the addition of serum (P<0.05) and reached minimum 48 hours later. The levels of MMP-9 and TIMP-1 in supernatant of culture medium of septic group significantly increased (P<0.01). The levels of MMP-9 and TIMP-1 increased in the septic group (P<0.01), while the level of TM reduced at the same time in septic group (P<0.01). Compared with septic group, the cell survival rate of TIMP-1 siRNA group decreased (P<0.05). The level of MMP-9 in supernatant of culture medium of TIMP-1 siRNA group increased (P<0.05), while the level of TIMP-1 decreased (P<0.05). The level of MMP-9 increased in TIMP-1 siRNA group (P<0.01), whereas the levels of TIMP-1 and TM reduced in TIMP-1 siRNA group (P<0.01). Conclusions: TIMP-1 plays a protective role in endothelial cells injury induced by septic serum. © 2018 Chinese Medical Association. All rights reserved.     

子宫内膜异位症中金属蛋白酶9及其特异性组织抑制因子的表达及临床意义

目的:探讨基质金属蛋白酶9(MMP-9)、金属蛋白酶特异性组织抑制因子1(TIMP-1)在子宫内膜异位症患者内膜标本中表达水平的变化及其临床意义。方法:收集子宫内膜异位症患者的异位内膜56例(观察组)和非内异症患者的子宫内膜标本18例(对照组),采用RT-PCR半定量方法检测内膜标本中MMP-9、TIMP-1 mRNA表达率及表达强度。结果:观察组和对照组所有内膜标本均有TIMP-1 mRNA表达;观察组和对照组标本中MMP-9 mRNA的表达率分别为58.9%和50%;观察组异位内膜中MMP-9 mRNA的表达强度高于对照组(P<0.05);TIMP-1 mRNA的表达强度低于对照组(P<0.05);对于MMP-9/TIMP-1比值,观察组明显高于对照组(P<0.01),早期(I-II期)明显高于III、IV期(P<0.01)。结论:子宫内膜异位症患者内膜中TIMP-1 mRNA的表达减弱,降低了对MMP-9的抑制作用;同时子宫内膜异位症患者内膜MMP-9 mRNA的表达增强,加强了其侵袭能力,易于发生种植转移,这些因素可能在子宫内膜异位症的发生发展过程中发挥重要作用。