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1.
Ascorbic Acid (Vitamin C) and Iloprost Attenuate the Lung Injury Caused by Ischemia/Reperfusion of the Lower Extremities of Rats 总被引:3,自引:0,他引:3
Baltalarli A Ozcan V Bir F Ferda B Aybek H Sacar M Onem G Goksin I Demir S Teke Z Zafer T 《Annals of vascular surgery》2006,20(1):49-55
The objectives of this study were to compare the protective effects of ascorbic acid and iloprost on lung injury caused by
ischemia reperfusion (I/R) of the lower extremities of rats. Wistar albino rats (n = 34) were divided into five groups. In the I/R group (n = 6), the aorta was cross-clamped for 3 hr, followed by 1 hr of reperfusion. In the vitamin C group (n = 8), animals were pretreated with 100 mg/kg ascorbic acid via the left jugular vein before aortic cross-clamping. In the
iloprost group (n = 8), animals were pretreated with 20 ng/(kg · min) iloprost by constant intravenous infusion via the left jugular venous
cannula. In the sham group (n = 6), the abdomen was left open at the same period and a juguler venous line was established. In the control group (n = 6), lungs were removed and blood samples taken immediately after sternotomy. No treatment was given in this group. After
both lungs were removed, biochemical parameters were measured and histopathological evaluation was made. Although the arterial
blood pO2 and HCO3 levels were stastistically significantly high in both the vitamin C and iloprost groups compared to the I/R group, plasma
malondialdehyde (MDA) levels were significantly low. Meanwhile, the MDA levels in the lung tissue were significantly low in
the vitamin C group compared to the I/R group. The MDA level in the lung tissue in the iloprost group was also low compared
to the I/R group, but it was not statistically significant. The lungs of the I/R group displayed intense interstitial leukocytic
infiltration in histopathological examination compared to the other groups. Pretreatment of animals with iloprost and vitamin
C significantly decreased the pulmonary injury characterized by decreased plasma leukocyte sequestration. The results suggest
that both vitamin C and iloprost are useful agents for attenuating the lung injury caused by increased oxidative stress and
neutrophil accumulation after a period of I/R of the lower extremities. 相似文献
2.
Bozkurt AK 《The Journal of cardiovascular surgery》2002,43(5):693-696
BACKGROUND: The aim of this study was to clarify the role of a-tocopherol (vitamin E) and iloprost on skeletal muscle ischemia/reperfusion injury. METHODS: Setting: animal research laboratory of a university hospital. Experimental design: the iliac arteries of the 24 adult Sprague-Dawley rats were clamped and 4 hours of ischemia followed by 1 hour of reperfusion was applied. In an attempt to decrease reperfusion injury, the rats were given either a-tocopherol (n=8), iloprost (n=6) and 8 rats were given normal saline and served as control group (n=8). Measures: blood pH, pO2, pCO2, HCO3, Na, K, creatine kinase (CPK), lactate dehydrogenase (LDH) values were determined at the end of the reperfusion period. Malondialdehyde (MDA), a product of lipid peroxidation, was measured in blood, muscle and lung as an indicator of free radicals. RESULTS: Blood pO2 and HCO3 levels were significantly high (p<0.05); CPK, LDH and MDA levels were significantly low (p<0.05) in both a-tocopherol and iloprost groups when compared to the control group. Similarly, the MDA levels in the gastrocnemius muscle were significantly low in both treatment groups when compared to the controls (p<0.05). There was no significant difference between groups in other parameters. CONCLUSIONS: The results suggest that, both a-tocopherol and iloprost are useful for attenuating oxidative muscle damage occurring after a period of ischemia/ reperfusion. 相似文献
3.
温血停搏液术终灌注对缺血再灌注心肌的保护作用 总被引:2,自引:0,他引:2
利用猫体外循环模型观察含甘露醇的温血停搏液术终灌注对缺血再灌注心肌的保护作用。心肌缺血恢复正常血液灌注前,从主动脉根部以5~6kPa的压力注入37℃含甘露醇的低钾温血停搏液50ml。结果显示用含甘露醇的温血停搏液术终灌注可保护缺血后再灌注心肌的功能,提高心肌能量储备,降低线粒体丙二醛含量。结论:含甘露醇的温血停搏液术终灌注,可提高心肌对氧自由基的清除能力,减轻线粒体膜脂质过氧化,提高心肌能量储备,有利于再灌注后心肌功能的恢复 相似文献
4.
Teke Z Aytekin FO Kabay B Yenisey C Aydin C Tekin K Sacar M Ozden A 《World journal of surgery》2007,31(9):1835-1842
Background Pyrrolidine dithiocarbamate (PDTC) is a low-molecular-weight thiol antioxidant and potent inhibitor of nuclear factor-κB (NF-κB)
activation. It has been shown to attenuate local harmful effects of ischemia/reperfusion (I/R) injury in many organs. In recent
animal studies, a delaying effect of remote organ I/R injury on the healing of colonic anastomoses has been demonstrated.
In this study we investigated whether PDTC prevents harmful systemic effects of superior mesenteric I/R on left colonic anastomosis
in rats.
Methods Anastomosis of the left colon was performed in 40 rats randomly allocated into the following four groups: (1) Sham-operated
group (group I, n = 10)—simultaneously with colonic anastomosis, the superior mesenteric artery and collateral branches divided from the celiac
axis and the inferior mesenteric artery were isolated but not occluded. (2) Sham+PDTC group (group II, n = 10)—identical to sham-operated rats except for the administration of PDTC (100 mg/kg IV bolus) 30 minutes prior to commencing
the experimental period. (3) I/R group (group III, n = 10)—60 minutes of intestinal I/R by superior mesenteric artery occlusion. (4) PDTC-treated group (group IV, n = 10)—PDTC 100 mg/kg before and after the I/R. On postoperative day 6, all animals were sacrificed, and anastomotic bursting
pressures were measured in vivo. Tissue samples were obtained for investigation of anastomotic hydroxyproline (HP) contents,
perianastomotic malondialdehyde (MDA) levels, myeloperoxidase activity (MPO), and glutathione (GSH) level.
Results There was a statistically significant decrease in anastomotic bursting pressure values, tissue HP content and GSH level, along
with an increase in MDA level and MPO activity in group III, when compared to groups I, II, and IV (p < 0.05). However, PDTC treatment led to a statistically significant increase in anastomotic bursting pressure values, tissue
HP content and GSH level, along with a decrease in MDA level and MPO activity in group IV (p < 0.05).
Conclusions This study showed that PDTC treatment significantly prevented the delaying effect of remote organ I/R injury on anastomotic
healing in the colon. Further clinical studies are needed to clarify whether PDTC may be a useful therapeutic agent for increasing
the safety of the anastomosis during particular operations where remote organ I/R injury occurs. 相似文献
5.
Pyrrolidine dithiocarbamate prevents 60 minutes of warm mesenteric ischemia/reperfusion injury in rats 总被引:1,自引:0,他引:1
Teke Z Kabay B Aytekin FO Yenisey C Demirkan NC Sacar M Erdem E Ozden A 《American journal of surgery》2007,194(2):255-262
BACKGROUND: Pyrrolidine dithiocarbamate (PDTC) is a low-molecular-weight thiol antioxidant and potent inhibitor of nuclear factor-kappaB (NF-kappaB) activation. It has been shown to attenuate harmful effects of ischemia/reperfusion (I/R) injury in many organs. In recent animal studies, destructive effects of reperfusion injury has been demonstrated. In this study, we aimed to investigate whether PDTC prevents harmful effects of superior mesenteric I/R injury in rats. METHODS: Wistar-albino rats were randomly allocated into the following 4 groups: (1) sham-operated group--these animals underwent laparotomy without I/R injury (group I, n = 12); (2) sham+PDTC group--identical to sham-operated rats except for the administration of PDTC (100 mg/kg intravenous bolus) 30 minutes prior to the commencement of the experimental period (group II, n = 12); (3) I/R group--these animals underwent laparotomy and 60 minutes of ischemia followed by 120 minutes of reperfusion (group III, n = 12); (4) PDTC-treated group (100 mg/kg, intravenously, before the I/R, group IV, n = 12). All animals were killed, and intestinal tissue samples were obtained for investigation of intestinal mucosal injury, myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, glutathione (GSH) levels, and intestinal edema. RESULTS: There was a statistically significant decrease in GSH levels, along with an increase in intestinal mucosal injury scores, MPO activity, MDA levels, and intestinal tissue wet-to-dry weight ratios in group III when compared to groups I, II, and IV (P < .05). However, PDTC treatment led to a statistically significant increase in GSH levels, along with a decrease in intestinal mucosal injury scores, MPO activity, MDA levels, and intestinal tissue wet-to-dry weight ratios in group IV (P < .05). CONCLUSIONS: This study showed that PDTC treatment significantly prevented the reperfusion injury caused by superior mesenteric I/R. Further clinical studies are needed to clarify whether PDTC may be a useful therapeutic agent to use in particular operations where the reperfusion injury occurs. 相似文献
6.
Effects of carbon dioxide pneumoretroperitoneum on free radical formation in remote organs and use of verapamil as an antioxidant 总被引:2,自引:0,他引:2
Guler C Samli M Aksoy Y Demirbas M Kilinç A Ellidokuz E Dincel C 《Journal of endourology / Endourological Society》2004,18(3):245-249
BACKGROUND AND PURPOSE: Pneumoretroperitoneum (Prp) acts as an ischemia/reperfusion (I/R) model. Ischemia/reperfusion (I/R) injury causes production of reactive oxygen species, which affect organs remote from the sites of I/R. The aim of this study was to assess the remote organ changes after Prp and to explore the effects of antioxidants. MATERIALS AND METHODS: Eighteen adult rabbits were randomized to three groups, each consisting of six rabbits. Group I (control) underwent balloon dissection of the left retroperitoneal space without gas insufflation. In group II (Prp), carbon dioxide at 10 mm Hg was applied for 2 hours after the balloon dissection (ischemia period) and for 1 hour after desufflation (reperfusion period). In group III (Prp + antioxidant), 5 minutes before the experiment, verapamil at 0.2 mg/kg was given intravenously and the same procedure was employed as in group II. Hepatic, pulmonary, opposite kidney, and treated kidney malondialdehyde (MDA) and reduced glutathione (GSH) levels were evaluated to show response to Prp. RESULTS: Pneumoretroperitoneum exerted oxidative stress on all tissues with an increase of MDA (P < 0.05) and a decrease of GSH (P < 0.05). The verapamil-treated group showed lower values of MDA (P < 0.05) and higher values of GSH (P < 0.05) than group II. CONCLUSION: Pneumoretroperitoneum increased oxidative stress in all remote organs tested. Verapamil reduced the oxidative stress. We concluded that Prp should be employed carefully in patients with limited vital organ capacity. Verapamil administration may be considered for protection against tissue injury attributable to oxidative stress in these patients. 相似文献
7.
目的 探讨远端缺血后处理对大鼠全脑缺血再灌注损伤的影响.方法 健康成年雄性SD大鼠128只,体重为200~ 250 g,采用随机数字表法,将其随机分为4组(n=32):假手术组(S组)、缺血再灌注组(I/R组)、I/R+远端缺血后处理组(I/R+ RIPoC组)以及远端缺血再灌注组(RI/R组).采用改良的Pulsinelli四动脉阻断法建立大鼠全脑缺血再灌注模型.S组不制备全脑缺血再灌注模型;I/R+ RIPoC组于再灌注开始行双侧股动脉缺血15 min,再灌注15 min,共计3个循环;RI/R组仅行双侧股动脉缺血15 min,再灌注15 min,共计3个循环.于再灌注24、48 h时取脑组织,行海马CA1区和额叶皮层凋亡细胞计数,测定海马CA1区Bcl-2和Bax的表达水平,并于再灌注48 h测定超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的活性及丙二醛(MDA)的含量;再灌注4d时行Morris水迷宫实验;再灌注7d时取脑组织,计算海马CA1区和额叶皮层神经元密度.结果 与S组比较,I/R组再灌注时凋亡细胞计数升高,Bcl-2和Bax表达上调,神经元密度、SOD和CAT活性降低,MDA含量升高,逃避潜伏期明显延长,穿越原平台次数与第2象限停留时间百分比降低(P≤0.Ol),RI/R组上述指标差异无统计学意义(P>0.05);与I/R组比较,I/R+ RIPoC组再灌注时凋亡细胞计数降低,Bcl-2表达上调,Bax表达下调,神经元密度、SOD和CAT活性升高,MDA含量降低,逃避潜伏期缩短,穿越原平台次数与第2象限停留时间百分比升高(P<0.01).结论 远端缺血后处理可减轻大鼠全脑缺血再灌注损伤,其机制与抑制脂质过氧化反应,调节Bcl-2与Bax的平衡抑制细胞凋亡有关. 相似文献
8.
内源性一氧化碳在大鼠肢体缺血再灌注致远隔多脏器氧化性损伤中的作用 总被引:4,自引:1,他引:4
目的 探讨内源性一氧化碳 (CO)在大鼠肢体缺血再灌注 (I/ R)致远隔多器官氧化性损伤中的作用机制。方法 将 6 4只大鼠随机分为 4组 :假手术 (Sham )组 ;Sham 特异性血红素氧化酶阻断剂—锌原卟啉 (Zn PP)组 ;肢体缺血 2小时和再灌注 4小时 (I/ R)组 ;I/ R Zn PP组。测定各组心、肺、肝和肾组织匀浆中丙二醛 (MDA )含量、超氧化物歧化酶 (SOD)活性及血液内碳氧血红蛋白 (COHb)的变化 ,观察动物 2 4小时存活率。结果 与 Sham组相比 ,I/ R组各脏器 MDA含量及血液内 COHb水平均显著增高 ,组织中 SOD活性和动物 2 4小时存活率显著降低 ,有统计学意义(P<0 .0 5 ) ;I/ R Zn PP组与 I/ R组相比各脏器 MDA含量进一步增高 ,血液内 COHb水平、组织中 SOD活性和动物的2 4小时存活率显著降低 ,也有统计学意义 (P<0 .0 5 )。结论 肢体缺血再灌注可导致多器官的氧化性损伤 ,并使 CO产生增多 ,后者在大鼠抗缺血再灌注所致的远隔多器官损伤中具有重要作用。 相似文献
9.
Jang YH Lee YC Park NH Shin HY Mun KC Choi MS Lee MY Kim AR Kim JM Lee SR Park HR 《Transplantation proceedings》2006,38(7):2190-2194
INTRODUCTION: The effect of epigallocatechin gallate (EGCG) in an in vivo renal model of ischemia with reperfusion (I/R) was compared between normotensive (WKR) and hypertensive (SHR) rats. METHODS: WKR (groups I, II, III) and SHR groups (groups IV, V, VI) were divided into three types. Groups I and IV were sham-operated animals; groups II and V were subjected to 45 minutes of renal I/R; and groups III and VI received 10 mg/kg EGCG intravenously at the time of reperfusion. Three days after renal I/R, we compared renal function markers, malondialdehyde (MDA), and histologic changes. RESULTS: Following renal I/R, levels of blood urea nitrogen (BUN) and serum creatinine (sCr) were increased and serum creatinine clearance (CrCl) decreased in group V compared to group II (P < .001). Those receiving EGCG treatment (groups III and VI) had decreased BUN and sCr compared to non-EGCG I/R groups (P < .001), but not surprisingly, higher than sham groups. CrCl was lowest in the SHR groups. The MDA was significantly decreased after EGCG treatment (P = .028 in group III, P = .002 in group VI). Following renal I/R, tissue necrosis was more severe among SHR (P < .001). However, the ratio of regeneration to damage significantly increased in SHR after EGCG treatment. CONCLUSIONS: The reperfusion injury was greater among SHR compared with WKR in terms of renal function, lipid peroxidation, and tissue damage. EGCG treatment significantly ameliorated renal impairment and promoted tissue regeneration following renal I/R. 相似文献
10.
Cytokines contribute to early hepatic parenchymal injury and microvascular dysfunction after bilateral hindlimb ischemia. 总被引:2,自引:0,他引:2
PURPOSE: Hepatic dysfunction may contribute to death from multiple organ dysfunction after abdominal aortic surgery. Several factors are likely responsible, and the purpose of this study was to determine whether the cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 (IL-1) are involved in initiating this remote hepatic injury. METHODS: In a normotensive rat model of 4-hour bilateral hindlimb ischemia/reperfusion (I/R), we measured systemic TNF-alpha and IL-1 levels throughout the I/R period. Rats were randomly assigned to either the 3-hour control group, the 3-hour I/R group, or the I/R group with administration of a polyclonal antibody (PAb) to TNF-alpha (I/R + TNF-alpha PAb). Direct evidence of lethal hepatocyte injury through the labeling of nuclei by propidium iodide (per 10(-1)mm(3)) and altered microvascular perfusion were assessed by using intravital microscopy. RESULTS: Systemic TNF-alpha peaked at 83.97 pg/mL (P <.05, n = 5) at 30 minutes of reperfusion and returned to baseline in 60 to 90 minutes. No significant change in systemic IL-1 was detected (P <.05, n = 4). Alanine aminotransferase increased 2.5-fold in the I/R group through 3 hours of reperfusion (P <.05, n = 4), and TNF-alpha PAb did not attenuate this alanine aminotransferase increase (P <.05, n = 6). Lethal hepatocyte injury increased by 8-fold in the I/R group compared with the control group (P <.05, n = 5), whereas TNF-alpha PAb significantly reduced this injury (P <.05, n = 4). No regional differences in injury were noted within the acinus. Total perfusion within the microvascular unit did not drop; however, significant flow heterogeneity was observed. The proportion of continuously perfused sinusoids declined in the I/R group after 3 hours of reperfusion in both periportal (62.0 +/- 2.2, P <.05) and, to a lesser, although significant, degree, in the pericentral regions (73. 2 +/- 1.73, P <.05). CONCLUSION: By scavenging extracellular TNF-alpha with a PAb, we provide direct evidence that TNF-alpha contributes to, but is not solely responsible for, early remote hepatocellular injury and microvascular dysfunction. The administration of TNF-alpha PAb reduced lethal hepatocyte injury in both regions of the acinus and also improved perfusion in the periportal region (76.8 +/- 5.41, P <.05), but not in the pericentral region. This suggests that TNF-alpha released during reperfusion mediates early remote hepatocellular injury and microvascular dysfunction after a remote ischemic insult. 相似文献
11.
Iloprost has been shown to minimize skeletal muscle necrosis when administered before the onset of ischemia in animal experiments, possibly by preventing neutrophil activation. Since patients with acute limb ischemia are seen after the process has begun, we investigated whether iloprost can be protective when given only during reperfusion. After anesthesia, 18 adult mongrel dogs underwent a standard isolated gracilis muscle preparation. In six control animals (group I) the gracilis muscle was subjected to 6 hours of ischemia followed by 48 hours of reperfusion. Group II animals (n = 6) received intravenous infusion of iloprost at a dose of 0.45 microgram/kg/hr beginning 1 hour before the onset of muscle ischemia and throughout the experiment (6 hours of ischemia and 1 hour of reperfusion). In addition to the continuous infusion, they received 0.45 microgram/kg intravenous boluses of iloprost 10 minutes before the induction of ischemia and 10 minutes before reperfusion. Group III animals (n = 6) had a similar ischemic interval, but were given a bolus of iloprost of 0.45 microgram/kg at end ischemia followed by continuous infusion of 0.45 microgram/kg/hr for 48 hours during reperfusion. Muscle biopsies were obtained at baseline and after 1 hour of reperfusion in all groups. Additional biopsies were obtained at 48 hours of reperfusion in groups I and III. Myeloperoxidase activity, a marker of neutrophil activation, was measured in all muscle biopsies. At the end of reperfusion, the gracilis muscle was harvested in all animals and weighed. Muscle necrosis was estimated by serial transection, nitroblue tetrazolium histochemical staining followed by computerized planimetry.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
12.
Protective Effect of Melatonin Against Ischemia/Reperfusion-Induced Oxidative Remote Organ Injury in the Rat 总被引:4,自引:0,他引:4
Purpose Oxygen free radicals are considered to be important components involved in the pathophysiological tissue alterations observed during ischemia/reperfusion (I/R). Based on the potent antioxidant effects of melatonin, we investigated the putative protective role of melatonin against I/R-induced oxidative remote organ injury.Methods Wistar albino rats were subjected to 1 h of infrarenal aortic occlusion followed by 1 h of reperfusion to induce I/R damage. Melatonin (10 mg/kg, s.c.) or vehicle was administered twice, 15 min prior to ischemia and immediately before the reperfusion period (I/R + Mel or I/R groups). At the end of the reperfusion periods, the rats were decapitated and hepatic, ileal, and lung tissue samples were removed for biochemical analyses of: malondialdehyde (MDA), an end product of lipid peroxidation; the glutathione (GSH) levels, a key antioxidant; and the myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. The serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured to evaluate the liver function. The wet/dry lung weight ratio was calculated to determine the extent of lung damage.Results The results revealed the occurrence of I/R-induced oxidative organ damage, as evidenced by increases in the MDA and MPO activity, and a decrease in GSH. Furthermore the AST, ALT levels, and the wet/dry lung weight ratio, which all increased due to I/R, were all observed to decrease after melationin treatment.Conclusion Since melatonin administration reversed these oxidant responses, it seems likely that melationin has a protective effect against oxidative organ damage induced by I/R. 相似文献
13.
Karabulut AB Kirimlioglu V Kirimlioglu H Yilmaz S Isik B Isikgil O 《Transplantation proceedings》2006,38(2):375-377
Resveratrol is as an antioxidant with free radical-scavenging activity and finds its clinical application in the prevention of postischemic tissue injury following solid organ transplantation. This study investigates the effect of Resveratrol on spleen and ileum tissues subjected to hepatic ischemia-reperfusion (I/R) in rats. Twenty-four rats were recruited in the study as follows: group A: I/R (n = 8), group B: I/R + Resveratrol (n = 8), and group C: sham operation (n = 8). After intraperitonealy pretreatment of eight rats with resveratrol (15 mg/kg/d) for 5 days, 16 rats were subjected to 45 minutes of hepatic ischemia followed by 30 minutes reperfusion period. Resveratrol was given 15 minutes prior to ischemia and just before the reperfusion in rats. After reperfusion period all rats were sacrificed. Spleen and ileum tissues were examined spectrophotometrically to measure malondialdehyde (MDA), glutathione (GSH), and total nitrite, nitrate as an end product of nitric oxide (NO) levels. Concerning the spleen, statistically significant decrease of GSH and increase of MDA and NO levels were found group A when compared to groups B and C (P = .040, P = .004, and P = .001 group A vs group B; P = .05, P = .003, and P = .001 group A vs group C, respectively). Parallel results were obtained in ileum. A statistically significant decrease in GSH and an increase in MDA and NO levels in group A in respect to group B and group C was obtained (P = .048, P = .034, and P = .001 group A vs group B; P = .004, P = .001, and P = .003 group A vs group C, respectively). The result of this study shows that resveratrol has a protective effect on spleen and ileal mitochondrial oxidative stress in rats subjected to I/R. 相似文献
14.
Olcay Eser Erdal Kalkan Murat Cosar Mehmet Yaman Sadik Büyükbaş Mustafa Cihat Avunduk Hüseyin Fidan 《European journal of trauma and emergency surgery》2007,33(4):414-421
Abstract
Objective: In this study, we aimed to delineate the mode of neuroprotective action of FK-506, and demonstrated that FK-506 could decrease
oxidative stress and apoptotic cell death in an in vivo rat model of neural ischemia-reperfusion after hemorrhagic shock.
Methods: Thirty rats were used as experimental subjects and divided into five equal groups. Group A rats (sham group, n = 6) were anesthetized
and craniotomies were performed for collecting brain tissue samples. In group B ischemia-reperfusion (I/R + 1 h, n = 6), group
C (I/R + 24 h, n = 6), group D (I/ R + 1 h FK-506, n = 6) and group E (I/R + 24 h FK-506, n = 6), systolic blood pressure
of the rats decreased to 40–50% of the normal level via bleeding from the femoral vein. Thus, a hemorrhagic shock and ischemic
neural tissue model was formed. The bloodwas retained and given to the remaining animals in groups B, C,Dand E via femoral
vein for reperfusion 20 min after the procedure. In group D and E, 1 mg/kg FK-506 in 0.5 ml isotonic solution was administered
to the rats 5 min before reperfusion. Group B and D rats were sacrificed after 1 h and group Cand E rats were sacrificed 24
h after reperfusion; the rats were sacrificed via bleeding associated with intracardiac puncture. Craniotomy was also performed
in groups B, C, D and E and brain tissue samples were fixed using neutral buffered 10% formaldehyde solution for immunohistopathological
examination as in group A. Brain tissue superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels, tissue myeloperoxydase
(MPO) activities and apoptotic cell analyses with Apo 2.7 immunohistochemically were also performed in all groups.
Results: The result of the study revealed that the SOD activities were lower for groups B (I/R + 1 h) and C (I/ R + 24 h) than for
group A (sham group) (p < 0.05). In addition, SOD activities were higher in groups D (I/ R + 1 h FK-506) and E (I/R + 24 h
FK-506) than in groups B (I/R + 1 h) and C (I/R + 24 h) (p < 0.05). MDA levels, MPO activities and the number of apoptotic
cells were lower in group A (sham group) than in groups B (I/R + 1 h) and C (I/R + 24 h) (p < 0.05). In addition to these
MDA levels, MPO activities and the number of apoptotic cells were higher in groups B (I/R + 1 h) and C (I/R + 24 h) as compared
to groups D (I/R + 1 h FK-506) and E (I/R + 24 h FK-506) (p < 0.05).
Conclusion: The results suggest that the prophylactic use of FK-506 in an in situ ischemic neural tissue may prevent reperfusion injury. 相似文献
15.
缺血预处理对大鼠移植胰腺缺血再灌注损伤的保护作用及其机制的研究 总被引:1,自引:0,他引:1
目的:探讨缺血预处理对大鼠移植胰腺冷缺血再灌注损伤和细胞凋亡的保护作用及其机制。方法:24只糖尿病SD大鼠随机分为缺血再灌注组(I/R组,n=6)和缺血预处理组(IPO组,n=18),IPO组又根据不同方法分为3个亚组:IPO1组(再灌注30s,缺血30s1次,n=6)、IPO2组(再灌注30s,缺血30s3次,n=6)和IPO3组(再灌注30s,缺血30s6次,n=6)。24只SD大鼠为供体,I/R组和IPO组均行同种胰腺移植。另取6只SD大鼠为对照组。检测各组再灌注前、后血糖及再灌注后2h移植胰腺组织中SOD和MDA含量;TUNEL法观察移植胰腺组织细胞凋亡情况,WesternBlot检测移植胰腺组织Bax和Bcl-2蛋白表达情况。结果:1)再灌注后IPO各组相对于I/R组血糖低(P〈0.05,P〈0.01,P〈0.05);IPO2组较IPO1组和IPO3组血糖低(P均〈0.05);2)再灌注后IPO组较I/R组移植胰腺组织中SOD含量高(P均〈0.01),MDA含量低(P均〈0.01),IPO2组相对于IPO1组和IPO3组SOD含量高(P均〈0.05)、MDA含量低(P均〈0.05)。3)再灌注后IPO组较I/R组移植胰组织中AI值低(P均〈0.01),IPO2组相对于IPO1组和IPO3组AI值低(P均〈0.05);4)I/R组胰组织Bax蛋白高表达,Bcl-2蛋白低表达,IPO各组再灌注后移植胰组织Bax蛋白低表达,Bcl-2蛋白高表达,而IPO2组Bcl-2蛋白表达最高,Bax蛋白表达最低。结论:缺血预处理对大鼠移植胰腺的缺血再灌注损伤具有保护作用,并可以减少移植胰腺缺血再灌注后的细胞凋亡,机制与减少氧自由基、上调Bcl-2蛋白和下调Bax蛋白有关。再灌注30s缺血30s重复3次是最佳的大鼠移植胰缺血预处理诱导办法。 相似文献
16.
Iloprost ameliorates post-ischemic lung reperfusion injury and maintains an appropriate pulmonary ET-1 balance. 总被引:3,自引:0,他引:3
Masahiro Kawashima Takayuki Nakamura Sven Schneider Brigitte Vollmar Henning F Lausberg Michael Bauer Michael D Menger Hans-Joachim Sch?fers 《The Journal of heart and lung transplantation》2003,22(7):794-801
BACKGROUND: Ischemia-reperfusion (I/R) injury of the lung involves increased pulmonary vascular resistance. Prostaglandins are thought to have a beneficial effect in lung transplantation, but their mechanism in I/R injury is unknown. We investigated whether iloprost, a stable prostacyclin analogue, prevents I/R-associated pulmonary vascular dysfunction and whether it affects endothelin-1 (ET-1) balance. METHODS: In an isolated blood-perfusion model, we subjected lungs of Lewis rats to 45 minutes of ischemia at 37 degrees C and randomly allocated the lungs to 3 groups (n = 6 each): iloprost (33.3 nmol/liter) added to the perfusate before ischemia and reperfusion (ILO+IR), iloprost (33.3 nmol/liter) given only before reperfusion (ILO+R), and controls without iloprost treatment (ILO-). RESULTS: Reperfusion induced marked pulmonary edema in non-treated controls (ILO-), which was attenuated in ILO+R lungs and completely prevented in ILO+IR lungs. At 60 minutes reperfusion, arterial oxygen tension was significantly greater in both ILO+R and ILO+IR lungs compared with ILO- controls. Mean pulmonary artery pressure and pulmonary vascular resistance were slightly decreased in the ILO+R and significantly decreased in the ILO+IR group compared with the ILO- controls. Plasma levels of big ET-1, measured in both afferent and efferent blood, showed that I/R results in increased pulmonary venous levels of big ET-1. Interestingly, the increased venoarterial ET-1 gradient in ILO- lungs decreased significantly in the ILO+IR group. CONCLUSIONS: We demonstrated in an isolated lung perfusion model that iloprost ameliorates post-ischemic lung reperfusion injury and maintains an appropriate pulmonary ET-1 balance. 相似文献
17.
C R Mohan E Ascer C P Marini R E Maughan M Gennaro 《The Journal of cardiovascular surgery》1992,33(5):613-618
Thromboxane is known to alter the endothelial cytoskeleton, thereby causing increased endothelial permeability and polymorphonuclear leukocyte (PMN) sequestration in the lungs. We investigated whether iloprost (a stable prostacyclin analog) can decrease thromboxane activity and consequently PMN sequestration because of its anti-platelet aggregation effect. This premise was investigated in a canine isolated gracilis muscle model using 18 animals. Six animals (group I) had the gracilis muscle subjected to 6 hours of complete ischemia followed by 48 hours of reperfusion. Group II (n = 6) received intravenous infusion of iloprost (0.45 micrograms/kg/hr) throughout the experiment (1 hour preischemia, 6 hours of ischemia and 1 hour of reperfusion) and boluses of 0.45 micrograms/kg 10 minutes before ischemia and reperfusion. Group III (n = 6) underwent a similar ischemic interval, but were given iloprost bolus of 0.45 micrograms/kg followed by intravenous infusion of 0.45 micrograms/kg/hr during 48 hours of reperfusion. Gracilis venous samples were obtained at preischemia (PI) and 1 hour of reperfusion (all 3 groups) and at 48 hours of reperfusion (groups I and III) to measure thromboxane (TXB2) levels. Muscle biopsies were taken at the same time to measure myeloperoxidase (MPO) activity, a marker of PMN infiltration. In group I, TXB2 level increased from a pre-ischemic value of 2983 +/- 1083 pg/ml to 9483 +/- 2218 pg/ml at 1 hour of reperfusion (p < 0.05) and then decreased to 2386 +/- 1533 pg/ml at 48 hours of reperfusion (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
18.
《Renal failure》2013,35(3):391-395
Ischemia/reperfusion (I/R) occurs in a number of pathological conditions, including myocardial infarction, stroke, aortic surgery, cardiopulmonary bypass surgery, organ transplantation, resuscitation, and critical care. Massive and abrupt release of oxygen-free radicals after reperfusion triggers oxidative damage. Before critical operations or after resuscitation, it would be wise to find a suitable prophylactic treatment to avoid I/R damage. We aimed to determine whether several commonly used intravenous anesthetics protect against renal I/R injury. Methods: Animals were randomly divided into seven groups, each consisting of six animals: sham group, control group, thiopental group, propofol group, intralipid group, etomidate group, and ketamine group. At the end of the 60-min ischemic period, 60 min reperfusion was established and the materials administered 15 min before the reperfusion. At the end of the reperfusion period, the samples of blood and tissue were reaped for biochemical and serological evaluation. Results: I/R procedure significantly increased malondialdehyde (MDA) levels, decreased catalase (CAT) activities, and superoxide dismutase (SOD) levels. The lowest MDA mean level was in the thiopental group and the highest MDA mean level was in control group. The lowest CAT mean level was in the intralipid group and the highest CAT mean level was in the etomidate group. The lowest SOD mean level was in the control group and the highest SOD mean level was in the propofol group. Conclusion: Thiopental and propofol, especially thiopental, are more effective to protect renal I/R injury. 相似文献
19.
Protective effects of hypovolemic hypotension preconditioning on cardiopulmonary function after myocardium ischemia/reperfusion injury 总被引:1,自引:0,他引:1
RDepartmentofAnesthesiology ,RenminHospital,WuhanUniversity,Wuhan 4 30 0 6 0 ,China (ChenXJ,WangX ,XiaZYandLuoT)DepartmentofCardiacSurgery ,RenminHospital,WuhanUniversity ,Wuhan 4 30 0 6 0 ,China (TuZF) Correspondingauthor:Tel:86 2 7 880 82 4 78,E mail:xue0 30 8@mail.tom .com .cnecentlyischemiapreconditioninghasprovedtoamelioratethesubsequentsustainedmyocardiumischemia reperfusioninjury .1,2 Someexperimentsreportedthatremoteorgansischemiapreconditioning(RPC) ,suchasinkidney ,can… 相似文献
20.
目的 探讨缺血后处理联合远隔缺血后处理对大鼠局灶性脑缺血再灌注损伤的影响.方法 成年雄性SD大鼠86只,体重270~330 g,随机分为5组,假手术组(Ⅰ组,n=19)仅实施手术,不行缺血再灌注;缺血再灌注组(Ⅱ组,n=19)阻断右侧大脑中动脉缺血1.5 h,再灌注24 h制备大鼠局灶性脑缺血再灌注损伤模型;Ⅲ组(n=16)再灌注前脑缺血30 s,再灌注30 s,重复3次;Ⅳ组(n=16)再灌注前右侧股动脉缺血5 min恢复灌注;V组(n=16)再灌注前行缺血后处理及远隔缺血后处理.于再灌注2和24 h时行神经功能缺损评分(NDS评分);再灌注24 h时断头取脑,测定脑梗死面积,检测脑组织微管相关蛋白2(MAP2)的表达水平;股静脉注射异硫氰酸,右旋糖酐,断头取脑,行共聚焦扫描,以对侧作为对照.结果 与l组比较,Ⅱ组、Ⅲ组、Ⅵ组和V组NDS评分和缺血侧脑梗死面积百分比明显升高,缺血侧脑组织MAP2表达水平、血浆容量、微血管直径和长度明显降低(P<0.05);与Ⅱ组比较,Ⅲ组、Ⅳ组和V组NDS评分和缺血侧脑梗死面积百分比明显降低,缺血侧脑组织MAP2表达水平、血浆容量、脑微血管直径和长度明显增加(P<0.05).结论 缺血后处理联合远隔缺血后处理可减轻大鼠局灶性脑缺血再灌注损伤,其效果与两者单独应用时相似. 相似文献