丙泊酚对全脑缺血/再灌注损伤大鼠保护作用研究

目的探讨丙白酚对大鼠全脑缺血/再灌注损伤（ischemia/reperfusion injury,I/RI）的保护作用。方法65只Wistar雄性大鼠采用完全随机法分为5组：假手术组（S组）、缺血/再灌注(ischemia/reperfusion,I/R)组(I/R)组、丙泊酚组1(P1)、丙泊酚组2(P2)、丙泊酚组...     

促红细胞生成素在大鼠脊髓缺血再灌注损伤中的表达及其意义

目的:观察促红细胞生成素(EPO)在大鼠脊髓缺血再灌注损伤(SCII)中的表达和重组人促红细胞生成素(rhuEPO)预处理对再灌注损伤脊髓神经细胞的作用。方法:将W ister大鼠分为正常组、假手术组、rhuEPO处理组和生理盐水对照组;rhuEPO处理组和生理盐水对照组于术前3h腹腔注射rhuEPO和生理盐水,制备大鼠脊髓缺血再灌注损伤模型。以免疫组化和W estern blot法检测脊髓组织中EPO的表达变化;以原位末端脱氧核糖核苷酸转移酶介导dUTP标记法(TUNEL法)检测细胞的凋亡情况。结果:EPO在无损伤脊髓中即有少量的表达,SCII后8h表达显著上调,于12、24h(12h与24h组比较差异无显著性意义,P>0.05)达高峰,伤后3d表达逐渐下调,5d仍保持较高水平。rhuEPO处理组SCII后8h、12h及24h时神经细胞凋亡水平明显低于生理盐水对照组,差异有显著性意义(P<0.01)。结论:在脊髓缺血再灌注损伤中EPO呈现时序性表达变化,可能是机体内源性神经保护的机制之一;EPO预处理能明显抑制SCII后神经细胞的凋亡。     

The protective effect of FK506 pretreatment against renal ischemia/reperfusion injury in rats.

The effect of pretreatment with FK506 on renal ischemia and reperfusion (I/R) injury was investigated using a rat model. Animals were assigned to one of two groups (20 rats each). Group 1 animals (controls) received 0.5 ml saline while group 2 animals received FK506 (0.3 mg/kg), administered intravenously 24 hr prior to the induction of renal ischemia. A 60-min period of ischemia of the right kidney was induced, and upon reperfusion a left nephrectomy was performed. Blood samples for estimation of BUN, creatinine, and tumor necrosis factor were collected on days 0 (preischemia), 1, 2, 3, 5, 7, and 10 (postischemia). Rats were sacrificed after day 10 and renal tissue was examined histologically. All animals survived the ischemic episode. FK506 pretreatment significantly reduced the serum levels of BUN (P less than 0.02), creatinine (P less than 0.02), and TNF (P less than 0.05) as compared with that seen in controls. Histologically, at day 10, the kidneys showed the expected sequelae of prior renal I/R with various degrees of tubular damage. However, no objective differences were evident between the two groups. Based upon these data, it can be concluded that (1) FK506 pretreatment ameliorates the functional renal injury associated with I/R, (2) renal ischemia induces the release of TNF, and (3) FK506 pretreatment results in a significant inhibition of TNF production. These data suggest that the release of TNF may be responsible for the increasing of BUN and creatinine levels seen after renal I/R and that pretreatment of renal donors with FK506 may improve renal function in the immediate post-transplant period.     

Montelukast protects against testes ischemia/reperfusion injury in rats

Introduction:

In this study, we investigate the effect of montelukast on histologic damage induced by testicular torsion-detorsion in rats.

Methods:

Twenty-one male Sprague-Dawley rats were separated into 3 groups, each containing 7 rats. A sham operation was performed in group 1 (control). In group 2 (ischemia-reperfusion [IR]/untreated), 1-hour detorsion of the testis was performed after 6 hours of unilateral testicular torsion. In group 3 (I-R/dextroamphetamine), after performing the same surgical procedures as in group 2, montelukast was given intraperitoneally. In all experimental rats, ipsilateral orchiectomies were performed for histological examination and tissue malondialdehyde (MDA), glutathione and myeloperoxidase assays.

Results:

Montelukast treatment significantly decreased the I-R-induced elevation in testes tissue MDA and glutathione levels were found to be preserved. The level of myeloperoxidase (MPO) activity was significantly increased in the testes tissue of the IR/untreated group. However, in I-R/montelukast treatment group significantly decreased testes tissue MPO level. Histopathologically, the in the group 2 rats, edema, congestion, hemorrhage between seminiferous tubules and necrosis of the germinal cells were predominant features in sections. However, most of the specimens in the montelukast treated group 3 showed grades-I and II injury. Additionally, the testicular injury score was lower in group 3 rats compared with group 2.

Conclusion:

The current findings demonstrate that the montelukast decreased the severity of testicular injury by reversing the oxidative effects of testes I-R.     

瑞芬太尼对缺血/再灌注损伤保护作用及可能机制的研究进展

背景 瑞芬太尼是一种新型的阿片受体激动剂,具有独特的快速起效和快速清除的优点,是麻醉过程中常用的镇痛药物.近来,发现瑞芬太尼对重要器官的缺血/再灌注损伤(ischemia/reperfusion injury,I/RI)具有保护作用. 目的 回顾瑞芬太尼的基本理化特点及药代学特点,并讨论其对I/RI的保护作用和可能的作用机制. 内容 大量研究表明瑞芬太尼对心脏、肝脏、神经系统和肾脏的I/RI均有保护作用.其作用机制尚未明了,可能与阿片受体、蛋白激酶C与ATP敏感性钾离子通道、一氧化氮与一氧化氮合酶、抗凋亡通道等有关. 趋向 瑞芬太尼对于I/RI的保护作用,将进一步增加其临床应用价值,也为围术期器官保护提供新的思路.     

等容血液稀释和川芎嗪对兔心肌缺血再灌注损伤的保护作用

目的 观察6％羟乙基淀粉(HAES)等客血液稀释和川芎嗪注射液对兔心肌缺血再灌注损伤的保护作用。方法 32只家兔随机分为4组(n=8):组Ⅰ(对照组);组Ⅱ(稀释组);组Ⅲ(川芎嗪组);组Ⅳ(稀释+川芎嗪组),观察在急性心肌缺血45min和再灌注180min状态下血浆及心肌组织中磷酸肌酸激酶(CPK)及乳酸脱氢酶(LDH)活性的变化,并以透射电镜观察心肌超微结构改变。结果缺血及再灌后,组Ⅰ血浆CPK、LDH活性进行性升高(P<0.05,P<0.01),缺血区心肌组织CPK、LDH活性明显降低(P<0.01)。再灌后与组Ⅰ相比,组Ⅱ、Ⅲ血浆LDH活性均降低(P<0.05),组Ⅱ缺血区心肌组织CPK、LDH活性均升高(P<0.05),组Ⅲ缺血区心肌组织CPK活性升高(P<0.05),组Ⅳ血浆CPK、LDH活性均降低(P<0.05,P<0.01),且LDH活性低于同期组Ⅱ(P<0.05),缺血区心肌组织CPK、LDH活性均显著升高(P<0.01),且CPK活性高于组Ⅲ缺血区(P<0.05)。心肌细胞超微结构可见组Ⅰ细胞结构破坏严重,组Ⅱ、Ⅲ结构破坏均较组Ⅰ轻,组Ⅳ结构基本接近正常。结论 6％HAES等容血液稀释和川芎嗪对心肌缺血再灌注损伤均有保护作用,二者合用保护作用更为显著。     

红景天甙对大鼠肾脏缺血再灌注损伤的保护作用

目的探讨红景天甙对大鼠肾脏缺血再灌注损伤（IRI）的预防和保护作用。方法将32只健康成年SD大鼠随机分成正常对照组、假手术组、缺血再灌注组和红景天甙组4组，每组8只。缺血再灌注组和红景天甙组分别制作肾脏缺血再灌注模型，红景天甙组予以红景天甙预处理。检测血中尿素氮（BUN）和肌酐（Scr）及肾脏中超氧化物歧化酶（SOD）、丙二酰二醛（MDA）和钠钾ATP酶（Na^＋-K^＋ATPase）含量，并用光镜和电镜观察肾脏组织形态学变化。结果红景天甙组血清BUN和Scr水平、肾皮质MDA含量较缺血再灌注组显著降低（P〈0．01），而肾皮质中SOD和Na^＋-K^＋ATPase含量与缺血再灌注组相比显著升高（P〈0．01）；肾组织光镜和电镜观察均见缺血再灌注组肾小球和肾小管上皮细胞损伤明显，而红景天甙组肾小球及肾小管仅见轻微损伤。结论红景天甙能有效降低大鼠肾脏缺血再灌注损伤（IRI），对肾脏IRI有明显的预防和保护作用，为临床上肾脏IRI提供新的预防和治疗思路。     

药物后处理对心肌缺血/再灌注损伤保护作用的研究与展望

背景随着心肌缺血/再灌注损伤（ischemia/reperfusion injury,I/RI）机制及心肌保护机制研究的深入,药物后处理作为一种更具有临床实用价值的心肌保护方法成为了研究热点。 目的阐述药物后处理用于心肌保护时,相关药物所模拟内源性保护机制的主要环节以及近年来药物后处理的研究概况和前瞻。 内容介绍药物后处理用于心肌保护时,主要途径、作用靶点以及相关药物。趋势药物后处理心肌保护机制的研究和深入将会发现更多的药物靶点,独特的操作便利性,必将更好的应用于临床服务于患者。     

姜黄素对肝缺血再灌注损伤保护作用的研究

目的探讨姜黄素对自体肝移植大鼠肝脏缺血再灌注损伤(IRI)的保护作用及其可能机制。方法54只SD雄性大鼠随机分为假手术(SO)组、自体肝移植模型姜黄素预处理(CU)组以及自体肝移植模型溶剂对照(CM)组,术后或再灌注2,6,24 h每组分别处死6只大鼠进行谷丙转氨酶(ALT)、谷草转氨酶(AST)、髓过氧化物酶(Myeloperoxidase MPO)的含量检测。结果血清ALT及AST水平,CM组及CU组均较SO组明显升高,但CM组又明显高于CU组;MPO在SO组含量明显低于CM组和CU组,而CU组又显著低于CM组。结论姜黄素对自体肝移植大鼠肝缺血再灌注损伤有保护作用,其机制可能与减轻中性粒细胞浸润有关。     

乳酸穿梭在心肌缺血/再灌注损伤中保护作用研究进展

背景 在传统观念上,乳酸是葡萄糖无氧代谢的废弃物,然而最近研究表明乳酸可作为能源物质,在体内能量代谢中有重要意义.在组织和细胞间存在大量乳酸穿梭现象,此种现象为机体代谢提供了保障. 目的 结合国内外相关研究,就乳酸穿梭机制在心肌保护中的作用进行阐述. 内容 乳酸是葡萄糖酵解的产物.乳酸穿梭是指机体不同组织和细胞间存在乳酸互相穿梭供能的现象.细胞间的乳酸转运主要由单羧酸转运蛋白(monocarboxylate transporter,MCT)、黏附分子(CD147)、乳酸脱氢酶组成.在心肌缺血/再灌注损伤(ischemia/reperfusion injury,I/RI)中乳酸穿梭主要是通过优化能量代谢及对Ca2+浓度的影响来发挥对心肌的保护作用. 趋向 目前研究发现乳酸在能量代谢中有重要意义,乳酸穿梭是机体I/RI时重要的能量代谢调节途径.但关于乳酸穿梭具体的调控机制研究尚少.     

钙网蛋白在不同预处理心肌细胞缺血再灌注的保护作用

目的 观察3种不同预处理对在体缺血再灌注心肌的保护作用,探讨钙网蛋白(CRT)在预处理心肌细胞缺血再灌注损伤的作用.方法 将30只成年SD大鼠随机分成5组(n=6),分别为缺血再灌注组、缺血预处理组、腺苷预处理组、远程预处理组和假手术组.建立大鼠在体缺血冉灌注损伤模型,观察各组缺血再灌注前后心功能变化,并检测再灌注末血清肌钙蛋白T(cTnT)、丙二醛(MDA)、超氧化物歧化酶(SOD)的变化以及心肌组织CRT的表达.结果 缺血预处理组、远程预处理组与缺血再灌注组比较(±dp/dt max)有明显提高(P<0.05).缺血预处理组、腺苷预处理组、远程预处理组cTnT、MDA值均低于缺血再灌注组,SOD值高于缺血再灌注组(P<0.05);腺苷预处理组SOD值高于缺血预处理组和远程预处理组,cTnT值则低于后2组(P<0.05);缺血预处理组、腺苷预处理组、远程组与缺血再灌注组比较,CRT表达灰度值均显著降低(P<0.05).结论 腺苷预处理、远程预处理均可以模拟缺血预处理的心肌保护作用;预处理可能通过下调钙网蛋白高表达减轻在体大鼠心肌细胞缺血再灌注损伤.     

Protective effects of anti-neutrophil antibody against myocardial ischemia/reperfusion injury in rats

Neutrophil activation initiates myocardial ischemia/reperfusion (I/R) injuries. The aim of this study is to evaluate the in vitro functions of an anti-neutrophil monoclonal antibody, Urge-8, and its therapeutic efficacy against myocardial ischemia (MI) in rats. We measured in vitro functions of rat neutrophils including chemotactic activity, superoxide production, phagocytic function, and neutrophil degranulation. MI was induced in Wistar rats by clamping the left coronary artery for 1 h. Rats received either isotype-negative control IgG(1) (control group, n = 20), 250 microg/kg of Urge-8 before (pre-treatment group, n = 20) or after (post-treatment group, n = 20) MI. The three groups were compared during the first 24 h after reperfusion with respect to changes in mean arterial pressure, heart rate, body temperature, biochemistry, serum cytokines, myocardial neutrophil infiltration, survival rate, and size of MI. Urge-8 effectively suppressed in vitro functions of rat neutrophils including chemotactic activity, superoxide production, phagocytic function, and neutrophil degranulation. The Urge-8 treated groups showed higher levels of arterial pressure and survival rate, lower values of interleukin-6 and interleukin-8, lower grade of myocardial neutrophil infiltration, and smaller MI size as compared to the control group. In conclusion, Urge-8 is effective against myocardial I/R injury by suppressing certain functions and myocardial infiltration of neutrophils in rats.     

肠缺血／再灌注损伤与防治措施

背景肠缺血／再灌（ischemia／reperfusion,I／R）损伤是外科实践中常见的组织器官损伤之一,在严重感染、创伤、休克、心肺功能不全等疾病的病理生理演变过程中起重要作用。目的就肠I／R损伤产生机制以及防治措施的研究进展进行综述,为今后临床工作提供指导。内容针对肠I／R损伤机制（氧自由基、能量缺乏、细胞内Ca^2＋超载、炎症反应、细胞异常凋亡）及其防御措施的研究进展展开论述。趋向肠I／R损伤是综合性原因引起,采取综合性防治措施可防治肠I／R损伤。     

沉默信息调节蛋白1在心肌缺血/再灌注中的保护作用

背景 沉默信息调节蛋白1 (silent information regulator protein 1,Sirt1)是尼克酰胺腺嘌呤二核苷酸(nicotinamide adenine dinucleotide,NAD)依赖的第3类组蛋白/非组蛋白去乙酰酶,参与细胞内多种生物功能的调节.Sirt1不仅在抗衰老中发挥重要作用,同样在心肌缺血/再灌注( ischemia/reperfusion,I/R)时保护受损细胞.目的 对Sirt1在心肌I/R中的保护机制以及几种激活Sirt1活性的方法进行综述. 内容 Sirt1能使活性氧清除剂产生增加、抗心肌细胞凋亡、促进细胞内自噬、减轻炎症反应、促进胞内正常线粒体合成等而减轻I/R的心肌细胞损伤.通过多种方法提高I/R时Sirt1的活性,是减轻损伤的重要措施. 趋向 随着Sin1在心肌I/R中的作用机制不断被揭示,其将成为缓解心肌I/R损伤的重要靶点.