乌司他丁对创伤失血性休克患者外周血单核细胞TOLL样受体4表达的影响

目的:观察乌司他丁对创伤失血性休克患者外周血单核细胞TOLL样受体4表达的影响,从而进一步了解乌司他丁抑制炎症反应的作用机制。方法:创伤失血性休克患者60例随机分为对照组(n=30)和乌司他丁组(n=30),乌司他丁组在麻醉诱导后切皮前静注乌司他丁30万U,对照组采用等量生理盐水。于麻醉诱导后切皮前,切皮后2h、4h,术后第1天、第2天、第3天采集动脉血,以流式细胞仪检测TLR4的表达变化,用ELISA试剂盒检测血浆TNF-α和IL-6浓度。结果:两组各时点CD14+单核细胞表面TLR4表达以及TNF-α、IL-6均较麻醉诱导后切皮前增加(P<0.05);乌司他丁组各指标值均较对照组上升幅度低(P<0.05)。结论:乌司他丁可有效抑制单核细胞表面TLR4的表达,抑制炎症因子的释放,对创伤失血性休克患者有一定的保护作用。     

乌司他丁对创伤失血性休克患者外周血单核细胞TOLL样受体4表达的影响

目的：观察乌司他丁对创伤失血性休克患者外周血单核细胞TOLL样受体4表达的影响，从而进一步了解乌司他丁抑制炎症反应的作用机制。方法：创伤失血性休克患者60例随机分为对照组（n=30）和乌司他丁组（n=30），乌司他丁组在麻醉诱导后切皮前静注乌司他丁30万U，对照组采用等量生理盐水。于麻醉诱导后切皮前。切皮后2h、4h。术后第1天、第2天、第3天采集动脉血。以流式细胞仪检测TLR4的表达变化。用ELISA试剂盒检测血浆TNF-α和IL-6浓度。结果：两组各时点CD14^＋单核细胞表面TLR4表达以及TNF-α、IL-6均较麻醉诱导后切皮前增加（P〈0．05）；乌司他丁组各指标值均较对照组上升幅度低（P〈0．05）。结论：乌司他丁可有效抑制单核细胞表面TLR4的表达，抑制炎症因子的释放，对创伤失血性休克患者有一定的保护作用。     

乌司他丁对重症中暑患者血管内皮细胞损伤的影响

目的：探讨乌司他丁对重症中暑患者血管内皮细胞损伤的保护作用。方法回顾性分析40例重症中暑患者的临床资料,其中20例患者采用常规治疗,为常规组,20例患者在常规治疗的基础上加用乌司他丁治疗,为乌司他丁组,比较两组治疗后外周CEC数量、外周血管vWF和TM浓度。另选择20例健康体检者作为对照组。结果治疗前重症中暑患者外周血CEC计数、vWF和TM浓度显著高于对照组（P＜0.01）,治疗后常规治疗组和乌司他丁组较治疗前均显著下降（P＜0.05或P＜0.01）,但乌司他丁组下降幅度显著大于常规治疗组（P＜0.01）。结论重症中暑患者在常规治疗的基础上加重乌司他丁治疗对患者的血管内皮细胞具有一定的保护作用。     

乌司他丁治疗急性胰腺炎临床疗效观察

目的评价乌司他丁对急性胰腺炎的疗效及临床应用价值.方法将56例急性水肿性胰腺炎患者,随机分成乌司他丁组(治疗组)30例,抑肽酶组(对照组)26例.观察两组患者的症状、体征消失时间及血、尿淀粉酶的下降情况.结果治疗组的上腹痛、上腹压痛缓解和消失及血、尿淀粉酶恢复正常时间均明显优于对照组,两者比较有显著差异.结论乌司他丁对急性胰腺炎有较好的疗效,有临床应用价值.     

乌司他丁对急性坏死性胰腺炎大鼠肺组织Toll样受体4表达的影响

目的 研究乌司他丁对急性坏死性胰腺炎肺组织Toll-样受体4(TLR4)表达的影响及其意义.方法 56只SD大鼠经逆行胰胆管注射5%牛磺胆酸钠(TAC)制作大鼠急性坏死性胰腺炎肺损伤动物模型,大鼠分为对照组(n=8)、急性坏死性胰腺炎组(n=24)和治疗组(n=24).对照组和急性坏死性胰腺炎组给予尾静脉注射生理盐水,治疗组给予尾静脉注射乌司他丁.分别测定各组血清淀粉酶和肺组织髓过氧化物酶(MPO)活性,计算肺组织学评分和肺损伤指数以评价肺损伤程度,荧光实时定量逆转录-聚合酶链反应(RT-PCR)检测各组不同时间点肺组织TLR4 mRNA表达.结果 与对照组比较,急性坏死性胰腺炎组大鼠各时点肺组织TLR4 mRNA表达明显增高(均P＜0.01),并在12 h达到峰值,同时肺组织MPO活性增高,肺损伤加重(P＜0.05或P<0.01).与急性坏死性胰腺炎组相比,治疗组肺组织TLR4 mRNA表达明显降低,肺损伤减轻,MPO活性降低(均P＜0.05).结论 急性坏死性胰腺炎时,肺组织内TLR4 mRNA表达明显上调,肺部炎症反应及肺损伤加重;乌司他丁可以降低急性坏死性胰腺炎大鼠肺组织TLR4 mRNA表达,减轻肺部炎症和肺损伤.     

乌司他丁对脓毒症患者C-反应蛋白及血管内皮生长因子表达的影响

目的研究乌司他丁对脓毒症患者C-反应蛋白(CRP)及血管内皮生长因子(VEGF)表达的影响.方法40例脓毒症患者随机分为常规治疗组和乌司他丁组各20例,两组均予以抗休克和病因治疗.在此基础上,乌司他丁组加用乌司他丁(20万U,每8小时1次,治疗7d),观察治疗前和治疗后的外周血CRP、VEGF与急性生理与慢性健康评分(APACHE I )的动态变化.结果治疗前两组外周血CRP及VEGF差异无统计学意义.常规治疗组第7天外周血CRP及VEGF分别为(59±28)ng/L,(97±28)ng/L;乌司他丁组治疗第7天外周血CRP及VEGF分别为(31±16)ng/L,(41±10)ng/L.乌司他丁组治疗后第7天的外周血CRP及VEGF较治疗前明显下降(P<0.05),且较常规治疗组下降明显(P<0.05).乌司他丁组治疗后第10天的APACHE I 评分[(11±6)分]明显低于常规治疗组[(15±7)分](P<0.05).结论乌司他丁可以降低脓毒症患者外周血CRP、VEGF与APACHE I 评分的水平,改善预后,其作用机制可能是通过降低血中的VEGF表达水平.     

乌司他丁对重症急性胰腺炎患者血浆D-二聚体的影响

目的 探讨乌司他丁对重症急性胰腺炎（SAP）患者血浆D-二聚体的影响。方法将60例无凝血功能障碍的SAP患者用抽签法随机分为2组：常规治疗组和乌司他丁组,乌司他丁组在常规治疗的基础上加用乌司他丁20万U静脉推注,每12h1次,维持应用7d。分别检测两组患者治疗前及治疗后第3天、第7天的血浆D-二聚体水平。结果治疗前两组患者血浆D-二聚体水平差异无显著性（P〉0．05）,但与对照组相比均显著升高（P＜0．01）;治疗后第3天、第7天,乌司他丁组血浆D-二聚体水平较常规治疗组显著下降（P＜0．05）。结论SAP患者血浆D-二聚体水平明显升高,乌司他丁能显著降低血浆D-二聚体水平,改善患者的凝血功能。     

老年危重患者在外科手术后早期应用乌司他丁的临床研究

目的　探讨乌司他丁在外科老年危重患者手术后早期应用的临床治疗作用。方法　将 30 例术后收入外科重症监护病房(ICU)的老年患者(>60 岁)随机均分为乌司他丁组和对照组,两组均给予外科 ICU的常规治疗。乌司他丁组在入 ICU后第1天加用40万U乌司他丁,第2、3、4 天分别加用 20 万 U乌司他丁。比较两组术后7 d内的临床症状、全身炎症反应综合征(SIRS)的改善情况和营养、免疫情况。结果　乌司他丁组预防应激性溃疡、改善SIRS症状以及减少蛋白分解的能力优于对照组。结论　乌司他丁对老年危重患者手术后的恢复治疗有一定积极作用。     

乌司他丁治疗老年性急性胰腺炎的临床观察

目的　观察乌司他丁治疗老年性急性胰腺炎的临床疗效。方法　将老年性急性胰腺炎患者随机分为两组 ,对照组 2 0例 (重症胰腺炎 5例 ,急性水肿性胰腺炎 15例 ) ,治疗组 2 1例 (重症胰腺炎 4例 ,急性水肿性胰腺炎 17例 )。对照组采用常规急性胰腺炎处理 ,治疗组采用常规急性胰腺炎处理加乌司他丁 10万U溶于 5 %葡萄糖 5 0 0ml,每天 2次 ,疗程 5 - 10天。结果　治疗组综合疗效评价达 90 .5 % ,对照组综合疗效评价 6 0 % ,两组比较有显著性差异性 (P <0 .0 5 )。早期使用乌司他丁能明显改善疗效、体征 ,血、尿淀粉酶 ,降低AST ,用药前后有显著性差异。结论　广谱胰酶抑制剂乌司他丁对老年性急性胰腺炎早期使用有较好的治疗作用 ,没有明显副作用     

乌司他丁联合参麦注射液治疗急性胰腺炎相关肺损伤的临床研究

目的 观察乌司他丁联合参麦注射液对急性胰腺炎相关急性肺损伤的临床治疗效果.方法 选取急性胰腺炎相关肺损伤患者60例,随机分为乌司他丁＋参麦组（US组）、乌司他丁组（U组）和对照组（C组）,每组20例.C组给予常规治疗,U组在常规治疗基础上每日静脉滴注乌司他丁（6000U/kg）,US组在常规治疗基础上每日静脉滴注乌司他丁（6000U/kg）和参麦注射液（0.6ml/kg）.分别于治疗前、治疗后第3、7天行动脉血气分析,计算氧合指数,测定血清TNF-α、IL-1β和IL-6浓度.结果 与C组比较,U组和US组治疗后3和7天血清TNF-α、IL-1β和IL-6浓度下降,治疗后7天氧合指数升高（P＜0.05）;与U组比较,US组治疗后7天血清TNF-α、IL-1β和IL-6浓度下降,氧合指数升高（P＜0.05）.结论 乌司他丁联合参麦注射液能进一步抑制炎性介质释放,减轻急性胰腺炎相关肺损伤.     

阿托伐他汀对慢性充血性心力衰竭患者外周血Toll样受体表达的影响

目的探讨慢性充血性心力衰竭(CCHF)患者外周血单个核细胞Toll样受体4(TLR4)表达改变情况及阿托伐他汀对其的干预效应。方法选取80例CCHF住院患者,其中40例按照标准治疗方案进行治疗(标准治疗组);另外40例在标准治疗的基础上口服阿托伐他汀20mg/d(阿托伐他汀组)。40名健康者为对照组。在治疗前和治疗后1个月,应用流式细胞仪检测外周血单个核细胞表面TLR4的表达,采用酶联免疫吸附试验检测血清肿瘤坏死因子(TNF)-α水平;并对TLR4的表达与血清TNF-α水平进行相关性分析。结果标准治疗组、阿托伐他汀组的外周血单个核细胞表面TLR4表达水平均较对照组显著升高(P值均<0.05),并且与血清TNF-α水平呈正相关(r=0.076,P<0.05)。治疗后1个月,标准治疗组和阿托伐他汀组的外周血单个核细胞表面TLR4的表达和血清TNF-α水平均较本组治疗前显著降低(P值分别<0.05、0.01),阿托伐他汀组的下降值均显著高于标准治疗组(P值均<0.05)。结论 TLR4表达可能与CCHF发生有关,阿托伐他汀可显著降低外周血单个核细胞表面TLR4的表达,提示阿托伐他汀的抗炎性免疫作用与抑制TLR4介导的炎性免疫反应有关。     

Effect of ω-3 Polyunsaturated Fatty Acid on Toll-like Receptors in Patients with Severe Multiple Trauma

This study examined the effects of ω-3 polyunsaturated fatty acid (ω-3PUFA) on the expression of toll-like receptor 2 (TLR2),toll-like receptor 4 (TLR4) and some related inflammatory factors in peripheral blood mononuclear cells (PBMCs) of patients with early-stage severe multiple trauma.Thirty-two patients who were admitted to the Department of Traumatic Surgery,Tongji Hospital (Wuhan,China) between May 2010 and November 2010,and diagnosed as having severe multiple trauma with a injury severity score (ISS) no less than 16,were enrolled in the study and divided into two groups at random (n=16 in each):ω-3PUFA group and control group in which routine parenteral nutrition supplemented with ω-3PUFA or not was administered to the patients in two groups for consecutive 7 days.Peripheral blood from these patients was collected within 2 h of admission (day 0),and 1,3,5 and 7days after the nutritional support.PBMCs were isolated and used for detection of the mRNA and protein expression of TLR2 and TLR4 by using real-time PCR and flow cytometry respectively,the levels of NF-κB by quantum dots-based immunofluorescence assay,the levels of TNF-α,IL-2,IL-6 and COX-2 by ELISA,respectively.The results showed that the mRNA and protein expression of TLR2 and TLR4 in PBMCs was significantly lower in ω-3PUFA group than in control group 5 and 7 days after nutrition support (both P＜0.05).The levels of TNF-α,IL-2,IL-6 and COX-2 were found to be substantially decreased in PBMCs in ω-3PUFA group as compared with control group at 5th and 7th day (P＜0.05 for all).It was concluded that ω-3PUFA can remarkably decrease the expression of TLR2,TLR4 and some related inflammatory factors in NF-κB signaling pathway in PBMCs of patients with severe multiple trauma,which suggests that ω-3PUFA may suppress the excessive inflammatory response meditated by the TLRs/NF-κB signaling pathway.     

NF-κB、TLR4在重症急性胰腺炎大鼠中的表达及乌司他丁腹腔灌洗对其影响作用的实验研究

目的：建立牛磺胆酸钠诱导的重症急性胰腺炎大鼠模型,观察NF-κB、TLR4在重症急性胰腺炎大鼠中的表达,以及乌司他丁腹腔灌洗对其影响作用。方法：将48只Wistar大鼠随机分为3组,每组各16只：假手术对照组（A组）、SAP模型组（B组）、乌司他丁腹腔灌洗组（E组）,各种处理后6 h、24 h取血液、腹水、胰腺组织测定IL-1β、TNF-α、淀粉酶、胰蛋白酶、NF-κB、TLR4水平,并作胰腺病理检查。结果：在SAP大鼠中NF-κB及TLR4表达均有明显增加,乌司他丁腹腔灌洗能减少TLR4、NF-κB的表达。结论：NF-κB及TLR4与胰腺病理损伤关系密切,在SAP发病机制中具有重要的枢纽作用;乌司他丁腹腔灌洗能减轻胰腺组织及全身的损害。     

乌司他丁减轻失血性休克大鼠肺炎性损伤的机制

目的探讨乌司他丁对创伤失血性休克大鼠肺炎性介质及其信号通路miR-146a/TLR4/NF-κB的影响。方法72只SD大 鼠,随机分为休克不复苏组（SR,n=24）,醋酸钠林格液组（AR,n=24）及乌司他丁组（UR,n=24）。通过股动脉放血将3组制成休 克模型（平均动脉压维持在30~40 mmHg）,SR组休克制备成功后不予复苏,并分别于休克后1、4、6 h（若大鼠死亡则大鼠死亡即 刻）取大鼠肺组织;AR组、UR组分别系维持休克60 min后应用醋酸钠林格液、醋酸钠林格液联合乌司他丁进行30 min液体复 苏,并分别于复苏后1、4、6 h取大鼠肺组织。利用实时荧光定量PCR法检测各组肺组织中miR-146a、TNF-α、IL-1、IL-4、IL-6、 IL-10的mRNA含量以及通过Western blot检测TLR4、MyD88、IκB-α、p-IκB-α、NF-κB p65、IRAK4、p-IRAK4（Thr345、Ser346）、 p-IRAK4（Thr342）、TRAF6的蛋白相对表达量。在光镜下观察3组肺组织病理学变化。结果与休克组相比,醋酸钠林格液组 肺组织炎症浸润程度稍减轻,其中miR-146a、IL-4 和IL-10 的mRNA水平升高（P<0.05）,IκB-α、p-IRAK4（Thr342）及p-IRAK4 (Thr345、ser346)的蛋白表达增加（P<0.05）;TNF-α、IL-1和IL-6的水平降低（P<0.05）,TLR4、MyD88、NF-κB p65、p-IκB-α、IRAK- 4及TRAF6的蛋白表达减少（P<0.05）。与醋酸钠林格液组比较,乌司他丁组的肺组织炎性损伤得到了进一步改善,升高了miR- 146a、IL-4 和IL-10 的mRNA水平（P<0.01）及IκB-α、p-IRAK4（Thr342）及p-IRAK4(Thr345、ser346)的蛋白表达（P<0.01）,降低 了TNF-α、IL-1和IL-6的水平（P<0.01）和TLR4、MyD88、NF-κB p65、p-IκB-α、IRAK-4及TRAF6的蛋白表达（P<0.01）。结论乌 司他丁联合醋酸钠林格液复苏创伤失血性休克大鼠可能是通过增强miR-146a的表达,负反馈调控TLR4/NF-kB信号通路,进而 调节体内促炎因子和抗炎因子平衡,以达到保护肺组织的作用。     

乌司他丁治疗重症急性胰腺炎32 例

目的探讨乌司他丁治疗重症急性胰腺炎(SAP)的临床疗效。方法76例SAP患者随机分为2组,对照组44例给予常规非手术治疗,治疗组32例在常规治疗基础上加用乌司他丁10万U溶于5%葡萄糖250 ml中静脉滴注,每日2次,连用7~12 d。结果两组血淀粉酶恢复、胃肠减压量无显著差异(P>0.05),治疗组患者受损器官的功能恢复时间明显短于对照组(P<0.05)。结论乌司他丁配合常规方法治疗SAP在改善受损器官的功能及预防多器官功能不全综合征的发生方面有较好的作用。     

Expression and Significance of Toll-like Receptor 2, 4 of Peripheral Blood Mononuclear Cells in Acute Abdomen Patients Associated with Systemic Inflammatory Response Syndrome

The changes of Toll-like receptor (TLR) 2, 4 of peripheral blood mononuclear cells (PBMCs) in the acute abdomen patients associated with systemic inflammatory response syndrome (SIRS) and their potential significance were explored. A clinical study was performed on 103 acute abdomen patients in whom 65 were associated with SIRS. Forty healthy individuals served as normal controls. The mRNA expression of TLR2, 4 was detected by RT-PCR, and the expression of TNF-αand EL-6 by ELISA. The level of plasma endotoxin, hospital stay and mortality were measured. It was found that the endotoxin level was increased to varying degrees in all the acute abdomen patients, and the endotoxin level was and hospital stay longer in SIRS group than in non-SIRS group (P<0.01). TLR2 mRNA, TLR4 mRNA, IL-6 and TNF-αcould be detected with low value in normal controls, but they were up-regulated markedly on the 1st day after admission. Then TLR4 mRNA, IL-6 and TNF-αwere decreased gradually, but TLR2 mRNA maintained at a high level till the 5th day. These indexes above in SIRS group were higher than those in non-SIRS group (P<0.01). The results of correlation analysis revealed the expression of TLR2, 4 mRNA was positively correlated with the levels of TNF-αand IL-6, and the hospital stay. The results of Logistic regression demonstrated that over-expression of TLR2, 4 mRNA might result in higher risk of multiple organ dysfunction syndrome (MODS). It was concluded that in the acute abdomen patients associated with SIRS, the expression of TLR2, 4 in PBMCs was increased markedly, suggesting that TLR might play an important role in the pathogenesis of acute abdomen associated with SIRS.     

乌司他丁对重症急性胰腺炎患者血清TNF-α、IL-6和hs-CRP的影响

目的:研究乌司他丁对重症急性胰腺炎(SAP)患者血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和高敏C-反应蛋白(hs-CRP)的影响。方法:80例SAP患者随机分成对照组和治疗组,每组40例。对照组给予西医常规治疗,治疗组在西医常规治疗的基础上加用乌司他丁,治疗10 d。观察治疗前后临床疗效,并分别在患者入院24 h内以及治疗7 d后采静脉血检测血清TNF-α、IL-6和hs-CRP的水平。结果:治疗后,治疗组临床疗效较对照组高(P<0.05);治疗7 d后,两组患者血清TNF-α、IL-6和hs-CRP水平均较治疗前显著降低(P<0.01),但治疗组下降更明显(P<0.01)。结论:乌司他丁可降低SAP患者血清TNF-α、IL-6和hs-CRP水平,抑制炎性反应。     

Effect of ω-3 polyunsaturated fatty acid on toll-like receptors in patients with severe multiple trauma

This study examined the effects of ω-3 polyunsaturated fatty acid(ω-3PUFA) on the expression of toll-like receptor 2(TLR2),toll-like receptor 4(TLR4) and some related inflammatory factors in peripheral blood mononuclear cells(PBMCs) of patients with early-stage severe multiple trauma.Thirty-two patients who were admitted to the Department of Traumatic Surgery,Tongji Hospital(Wuhan,China) between May 2010 and November 2010,and diagnosed as having severe multiple trauma with a injury severity score(ISS) no less than 16,were enrolled in the study and divided into two groups at random(n=16 in each):ω-3PUFA group and control group in which routine parenteral nutrition supplemented with ω-3PUFA or not was administered to the patients in two groups for consecutive 7 days.Peripheral blood from these patients was collected within 2 h of admission(day 0),and 1,3,5 and 7 days after the nutritional support.PBMCs were isolated and used for detection of the mRNA and protein expression of TLR2 and TLR4 by using real-time PCR and flow cytometry respectively,the levels of NF-κB by quantum dots-based immunofluorescence assay,the levels of TNF-α,IL-2,IL-6 and COX-2 by ELISA,respectively.The results showed that the mRNA and protein expression of TLR2 and TLR4 in PBMCs was significantly lower in ω-3PUFA group than in control group 5 and 7 days after nutrition support(both P<0.05).The levels of TNF-α,IL-2,IL-6 and COX-2 were found to be substantially decreased in PBMCs in ω-3PUFA group as compared with control group at 5th and 7th day(P<0.05 for all).It was concluded that ω-3PUFA can remarkably decrease the expression of TLR2,TLR4 and some related inflammatory factors in NF-κB signaling pathway in PBMCs of patients with severe multiple trauma,which suggests that ω-3PUFA may suppress the excessive inflammatory response meditated by the TLRs/NF-κB signaling pathway.     

阿托伐他汀对2型糖尿病患者外周血单核细胞TLR4表达的影响

目的探讨阿托伐他汀对2型糖尿病的抗炎作用机制是否与抑制toll样受体4（TLR4）有关。方法将40例2型糖尿病患者随机分为常规治疗组和阿托伐他汀治疗组。阿托伐他汀治疗组患者在常规治疗基础上给予阿托伐他汀20 mg,1次/d,晚间口服。治疗前及治疗1月后采血,应用流式细胞仪检测外周血单核细胞TLR4蛋白表达;应用酶联免疫（ELISA）法检测血浆肿瘤坏死因子-α（TNF-α）浓度。结果单核细胞TLR4蛋白与血糖,糖化血红蛋白及血浆TNF-α呈正相关。治疗1月后,阿托伐他汀治疗组和常规治疗组血糖、外周血单核细胞TLR4蛋白及血浆TNF-α浓度均较治疗前降低（P〈0.05）;阿托伐他汀治疗组单核细胞TLR4蛋白和血浆TNF-α均低于常规治疗组（P〈0.05）。结论阿托伐他汀能下调2型糖尿病患者的单核细胞TLR4表达,降低血浆炎症因子水平。其抗炎作用可能与抑制单核细胞TLR4通路有关。