无创远程肢体缺血联合处理对大鼠肾脏急性缺血再灌注损伤的保护作用

目的 探讨无创远程肢体缺血联合处理对大鼠肾脏急性缺血再灌注损伤的保护及作用机制.方法 30只健康雄性SD大鼠,随机分为3组(每组10只):A组为假手术组(Sham组)、B组为缺血再灌注组(IR组)、c组为无创远程肢体缺血联合处理组(RIperC+ RIpostC组).再灌注24h测定血清中肌酐(cr)和尿素氮(BUN)含量,肾脏组织中髓过氧化物酶(MPO)活力、丙二醛(MDA)含量和超氧化物歧化酶(SOD)活力并在光镜下观察肾脏组织形态学变化.结果 B组的Cr(429.52±29.08) μmol/L、BUN(39.05± 2.23) mmol/L、MPO(7.31±1.48) U/g、MDA (3.94±0.48) nmoL/mgprot均高于A组Cr(103.91±21.45)μmol/L(P＜0.001)、BUN(12.20±1.86) mmol/L(P＜0.001)、MPO(2.25±0.89) U/g(P=0.009)、MDA(1.95±0.29) nmol/mgprot(P=0.003);而SOD(4.03±0.38) U/mgprot低于A组SOD(6.819±0.68) U/mgprot(P=0.003).c组的Cr(244.85±40.30) μmol/L(P=0.002) 、BUN(23.48±1.80) mmol/L(P＜0.001)、MPO(3.65±0.73) U/g(P =0.045)、MDA(2.19±0.31) nmol/mgprot(P=0.006)均低于B组,而SOD(5.71±0.30) U/mgprot(P=0.003)高于B组.A组组织形态基本正常,c组组织形态学改变较B组明显减轻.结论 无创远程肢体缺血联合处理对肾脏急性缺血再灌注损伤有显著保护作用.其保护作用可能通过对肢体短暂的缺血再灌注激发了机体内源性的抗氧化能力,从而达到减轻肾脏的急性缺血再灌注损伤.     

PI3K－Akt 信号通路在内皮祖细胞移植减轻大鼠缺血再灌注肾损伤中的作用

目的探讨磷脂酰肌醇－3－激酶－丝氨酸／苏氨酸激酶（ PI3K－Akt）信号通路在内皮祖细胞（ EPC）移植减轻大鼠缺血再灌注肾损伤中的作用。方法抽取大鼠外周血,采用密度梯度离心的方法分离、培养内皮组细胞。22只雄性SD大鼠随机分为正常对照组、缺血再灌注（ I／R）组、EPCs移植组3组,分别于术后第1 d收获所有大鼠肾脏标本和血标本。流式细胞仪及细胞免疫荧光鉴定 EPC 表面标志（ CD34／VEGFR－2）;测定血标本尿素氮和肌酐值;行western bolt检测各组大鼠p－AKT蛋白的表达情况。结果与正常对照组比较,其余各组血肌酐及尿素氮均升高,I／R组、EPC组肾脏p－Akt表达上调（ P ＜0．05）;与I／R组比较,EPC组的肌酐及尿素氮降低,p－Akt表达上调（ P ＜0．05）。结论 EPC移植可能通过激活PI3K－Akt信号通路减轻大鼠缺血再灌注肾损伤。     

Ischemic preconditioning-mediated cardioprotection is disrupted in heterozygous Flt-1 (VEGFR-1) knockout mice

This study attempts to address an important clinical issue by identifying potential candidates of VEGF signaling through Flt-1 receptor that trigger angiogenic signal under ischemic stress. To determine the significance of VEGF-Flt-1 (VEGFR1) signaling in ischemic preconditioned (PC) myocardium, we used heterozygous Flt-1 knockout (KO) mice to dissect the pathway and identify candidate genes involved in VEGF signaling. DNA microarrays were employed to detect, characterize and distinguish altered myocardial gene expression by comparing between wild type (WT) CD-1 and heterozygous Flt-1 KO mice when exposed to ischemia (30 min) and reperfusion (2 h). Moreover, KO mice demonstrated reduced beneficial effects of PC when compared to the WT with PC. In the KO and WT mice, the % recovery of the left ventricular developed pressure and the maximum first derivative of the developed pressure after ischemia/reperfusion without PC were similar. However, when animals were subjected to PC, the left ventricular functional recovery throughout the reperfusion period was significantly lower in KO mice than in WT mice. These results indicate for the first time that in the heterozygous Flt-1 KO mice, PC is not as effective as that found in WT. This observation may be due to downregulation of several important genes such as growth-regulated oncogene 1 (Gro1), heat shock proteins (HSP), I kappa B kinase beta (IKK beta), colony-stimulating factor-1 (CSF-1) and annexin A7, suggesting the importance of VEGF-Flt-1 receptor signaling during PC.     

Metalloproteinase expression after desflurane preconditioning in hepatectomies: A randomized clinical trial

BACKGROUNDHepatectomy with inflow occlusion results in ischemia-reperfusion injury; however, pharmacological preconditioning can prevent such injury and optimize the postoperative recovery of hepatectomized patients. The normal inflammatory response after a hepatectomy involves increased expression of metalloproteinases, which may signal pathologic hepatic tissue reformation. AIMTo investigate the effect of desflurane preconditioning on these inflammatory indices in patients with inflow occlusion undergoing hepatectomy.METHODSThis is a single-center, prospective, randomized controlled trial conducted at the 4^th Department of Surgery of the Medical School of Aristotle University of Thessaloniki, between August 2016 and December 2017. Forty-six patients were randomized to either the desflurane treatment group for pharmacological preconditioning (by replacement of propofol with desflurane, administered 30 min before induction of ischemia) or the control group for standard intravenous propofol. The primary endpoint of expression levels of matrix metalloproteinases and their inhibitors was determined preoperatively and at 30 min posthepatic reperfusion. The secondary endpoints of neutrophil infiltration, coagulation profile, activity of antithrombin III (AT III), protein C (PC), protein S and biochemical markers of liver function were determined for 5 d postoperatively and compared between the groups.RESULTSThe desflurane treatment group showed significantly increased levels of tissue inhibitor of metalloproteinases 1 and 2, significantly decreased levels of matrix metalloproteinases 2 and 9, decreased neutrophil infiltration, and less profound changes in the coagulation profile.  During the 5-d postoperative period, all patients showed significantly decreased activity of AT III, PC and protein S (vs baseline values, P < 0.05). The activity of AT III and PC differed significantly between the two groups from postoperative day 1 to postoperative day 5 (P < 0.05), showing a moderate drop in activity of AT III and PC in the desflurane treatment group and a dramatic drop in the control group. Compared to the control group, the desflurane treatment group also had significantly lower international normalized ratio values on all postoperative days (P < 0.005) and lower serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase values on postoperative days 2 and 3 (P < 0.05).   Total length of stay was significantly less in the desflurane group (P = 0.009).CONCLUSIONDesflurane preconditioning can lessen the inflammatory response related to ischemia-reperfusion injury and may shorten length of hospitalization.     

Prise en charge de l’infarctus du myocarde en 2012

Improvement of myocardial reperfusion with a greater use of primary percutaneous coronary intervention, adjunctive pharmacological and mechanical therapies have contributed to a spectacular decrease in mortality of patients presenting with ST-elevation myocardial infarction.     

Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

OBJECTIVE:

It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage.

METHODS:

We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student''s t-test.

RESULTS:

The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group.

CONCLUSION:

For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion.     

The Protective Effect of St. Thomas Cardioplegia Enriched With Zacopride on the Isolated Rat Heart

The activation of the heart inward rectifier potassium channel (I_K1) can reduce the injury of myocardial cells by shortening the action potential duration and reducing intracellular calcium overload. Zacopride is a selective I_K1 agonist and suppresses triggered arrhythmias in rat hearts. This investigation studied the effects of St. Thomas (ST) cardioplegia enriched with Zacopride on the isolated rat heart model. Sprague‐Dawley rat hearts were harvested and perfused for 20 minutes with 37°C Krebs‐Henseleit (KH) buffer followed by 15 minute perfusion with 4°C calcium‐free KH buffer in the Control group (Con, n = 8), ST cardioplegia in the ST group (ST, n = 8) and ST cardioplegia with Zacopride in the STZ group (STZ, n = 8). After 45 minutes of arresting, all hearts were reperfused with 37°C KH buffer for 60 minutes. Hearts in the STZ group arrested faster than the Con and ST groups (9.25 ± 2.38 s vs. 72.25 ± 8.1 s, 12.75 ± 2.87 s). The recovery of the left ventricular developed pressure, ± dP/dtmax, heart rate, and coronary flow in the STZ group is significantly better than the other two groups during reperfusion. Compared with the Con and ST groups, the STZ group showed significant decreases in the maximum carciac troponin I level (P < 0.05) and the infarct size (P < 0.05). The superoxide dismutase level in the STZ group increased during the first 20 minutes of reperfusion (P < 0.05). ST cardioplegia enriched with Zacopride has beneficial effects against ischemia‐reperfusion injury in this isolated rat heart model.     

乌司他丁减轻无心跳大鼠供肺缺血再灌注损伤的作用及机制

目的 研究乌司他丁(UTI)减轻无心跳大鼠供肺缺血再灌注损伤作用及作用机制.方法 选取雄性SD大鼠作为供、受鼠建立无心跳大鼠左肺移植模型,将受鼠分为对照组和实验组,对照组受鼠接受的供肺经低钾右旋糖酐(LPD)液灌注和保存,实验组受鼠接受的供肺经含乌司他丁(50万U/L)的LPD液灌注和保存.移植过程中监测受鼠的动脉血氧合情况;移植肺再灌注30 min和1h时,取两组受鼠移植肺组织,测量和计算湿干质量比,检测移植肺组织中丙二醛(MDA)和超氧化物歧化酶(SOD)含量;提取RNA,采用实时定量聚合酶链反应检测移植肺组织中肿瘤坏死因子-α(TNF-a)、细胞间黏附分子-1(ICAM-1)和白细胞介素10(IL-10) mRNA的相对表达量.结果 再灌注后1h,实验组的氧合指数(PaO2/FiO2)为472.38±31.66,显著高于对照组的429.52±14.83,两组比较,差异有统计学意义(P=0.025).与对照组相比,实验组在再灌注30 min和1h时的水肿情况(湿干质量比)均好于对照组(P=0.005,P=0.006),实验组移植肺组织病理损伤也明显轻于对照组.不论再灌注30 min还是1h,实验组移植肺组织中MDA含量较对照组显著降低(P=0.039,P=0.006),而SOD含量显著升高(P=0.035,P=0.030).再灌注30 min时,实验组TNF-a的表达较对照组显著下降(P=0.000),再灌注1h时下降不明显(P=0.139);再灌注30 min时,ICAM-1水平较对照组下降不明显(P=0.062),再灌注1h则存在明显降低(P=0.001);再灌注30 min和1h时,实验组IL-10 mRNA的表达水平均较对照组显著上调(P=0.004,P=0.000).结论 乌司他丁能够减轻无心跳大鼠供肺的缺血再灌注损伤,对移植肺有保护作用.     

右美托咪定的心脏保护作用

右美托咪定为高选择性α2受体激动剂,具有镇静、镇痛、抗焦虑、抑制交感神经兴奋等作用,现作为麻醉辅助药用于手术和ICU镇静。近期研究发现右美托咪定具有心脏保护作用,如抗缺血再灌注损伤、抗心律失常,从而总体上降低术后心脏相关并发症的发生。其抗缺血再灌注损伤作用机制一方面可能与抑制中枢的交感活性,降低心率、增加氧供、降低氧耗相关,另一方面可通过缺血预处理机制,激活相关促存活信号通路抗缺血再灌注损伤。同时,使用该药后儿茶酚胺释放减少,迷走神经相对兴奋,可降低手术及麻醉操作引起的应激反应,并可与咪唑啉受体结合,使其具有抗心律失常作用。总体而言,其保护作用的确切机制尚不明确,故将来需深入分子及基因水平进行机制研究。     

NADPH氧化酶与脑缺血再灌注损伤

NADPH氧化酶类是一个多亚基酶复合体家族,催化活性氧(reactive oxygen species,ROS)的产生.大量研究显示,氧化应激在脑缺血再灌注损伤中起着十分重要的作用.而一些关于NADPH氧化酶在脑缺血后表达改变的发现,为缺血性卒中的防治提供了新的思路.NADPH氧化酶有可能会成为一个新的治疗靶点.