Mesna protects splanchnic organs from oxidative stress induced by pneumoperitoneum

Background  We investigated the potential beneficial effect of the antioxidant 2-mercaptoethane-sulfonate (mesna) against oxidative stress induced by pneumoperitoneum in splanchnic organs. Methods  Wistar rats were subjected to either (a) CO₂ pneumoperitoneum (15 mmHg for 60 min) (group P), (b) pretreatment with mesna (400 mg/kg, p.o.) followed by pneumoperitoneum with a 180 min interval (group MP), (c) sham operation (group S), or (d) administration of mesna only (group M). Forty-five minutes after desufflation (groups P and MP), 60 + 45 min after the induction of anesthesia (group S), or 180 min after mesna administration (group M), tissue specimens were excised from liver, kidneys, jejunum and stomach. Tissue oxidative state was assessed on the basis of glutathione-to-glutathione disulfide ratio, malondialdehyde concentration , and superoxide dismutase activity. Results  Pneumoperitoneum deteriorated all the oxidative stress markers in the organs studied. Mesna prevented the occurrence of oxidative stress following pneumoperitoneum in all the organs studied. In the absence of pneumoperitoneum, the administration of mesna caused mild enhancement of the oxidative state of liver, stomach, and kidneys compared to sham controls. Conclusions  Prophylaxis with mesna prevents oxidative stress induced by pneumoperitoneum in splanchnic organs.     

The effect of pentoxifylline on oxidative stress in CO2 pneumoperitoneum

Background  Carbon dioxide (CO₂) pneumoperitoneum induces peritoneal oxidative stress. This experimental, randomized, controlled study was designed to investigate the effect of pentoxifylline on oxidative stress induced by CO₂ pneumoperitoneum. Methods  For this study, 36 Swiss albino rats were randomized into three groups. Arteria, vena femoralis, and peritoneal cavity were cannulated after anesthesia. The arterial pH, partial arterial oxygen pressure (PaO₂), venous PO₂, arterial and venous PO₂ difference (P_(a-v)O₂), serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and thiobarbituric acid-reactive substances (TBARS) were studied at the end of the first and second hours in group 1 (control). In group 2, 1 cc isotonic NaCl was injected into peritoneal cavity and then CO₂ pneumoperitoneum was established. At the end of the first hour of insufflation and one hour after desufflation, the same parameters as in group 1 were studied. In group 3, the CO₂ pneumoperitoneum plus pentoxifylline group, all procedures as in group 2 were repeated, with the exception of pentoxifylline (50 mg/kg) injected in place of saline. Results  At the end of the first hour, P_(a-v)O₂ value in group 2 was significantly less than in the control group (group 1) and group 3 (p < 0.05). There were no significant differences in PaO_2, pH, AST, and ALT values between groups (p > 0.05). TBARS level in group 1 was significantly lower than in the other groups, but there was no significant difference in TBARS level between groups 2 and 3. At the end of the second hour, TBARS level in group 3 was significantly lower than in group 2 (p < 0.05). Conclusions  Pentoxifylline may reduce the oxidative injury following laparoscopic procedures.     

CO2气腹对慢性肺功能不全兔肺组织氧化应激反应影响的实验研究

目的探讨CO2气腹对慢性肺功能不全兔肺组织氧化应激反应的损伤机制。方法兔肺气肿模型稳定后，施加CO2气腹2h，压力为10mmHg和15mmHg。分别于气腹解除即时、2h、6h和18h各时间点测定肺组织中SOD、GSH—PX、MPO、CAT活力和MDA、GSH含量。结果在气腹作用后即时肺组织中SOD、CAT、GSH—PX活力和GSH含量开始下降，至气腹2h后达最低，后开始增高，但18h后仍未恢复到气腹前水平。而MDA含量和MPO活力变化则相反。在15mmHg压力下上述指标变化更为显著。结论在CO2气腹条件下肺组织缺血、缺氧，活性氧自由基生成增加，氧化应激反应增强，导致了肺功能的损伤。气腹压力越高，损伤程度越显著。     

Aprotinin reduces injury of the spinal cord in transient ischemia

Objective: The protective effect of aprotinin, which is a protease inhibitor, was assessed in a rabbit spinal cord ischemia model. Design: Randomized, controlled, prospective study. Setting: University research laboratory. Subjects: New Zealand white rabbits (36) of both sexes. Methods: In 24 animals, ischemia was induced with midline laparotomy and clamping the aorta just distal to left renal artery and proximal to aortic bifurcation for 20 min. Aprotinin was given 30 000 KIU as a short intravenous injection after anesthesia, and was followed by 10 000 KIU/h by continuous infusion in group 1 (n=12). Similar volume of saline solution was used in control group of animals (group 2, n=12). Group 3 of animals (sham group, n=12) were anesthetized and subjected to laparotomy without aortic occlusion. Physiological parameters and somatosensory evoked-potentials (SEP) were monitored in animals before ischemia, during ischemia and in the first 60 min of reperfusion. Their neurological outcome was clinically evaluated up to 48 h postischemia. Their motor function was scored, and the intergroup differences were compared. The animals were sacrificed after two days of postischemia. Their spinal cord, abdominal aorta, and its branches were processed for histopathological examination. Results: In group 3, SEP amplitudes did not change during the procedures, and all animals recovered without neurologic deficits. At the end of ischemic period, the average amplitude was reduced to 53±7% of the baseline in all ischemic animals. This was followed by a gradual return to 89±8 and 81±13% of the initial amplitude after 60 min of reperfusion in group 1 and group 2 correspondingly (P>0.05). The average motor function score was significantly higher in group 1 than group 2 at 24 and 48 h after the ischemic insult (P<0.05). Histological observations were clearly correlated with the neurological findings. Conclusion: The results suggest that aprotinin reduces spinal cord injury and preserves neurologic function in transient spinal cord ischemia in rabbits.     

地氟醚对内毒素诱导大鼠肺组织氧化应激反应的影响

目的探讨地氟醚对内毒素（LPS）诱导大鼠肺组织氧化应激反应的影响。方法雄性Wistar大鼠48只,体重200～290 g,随机分为4组（n=12）,对照组（C组）股静脉注射生理盐水1.2ml后机械通气4 h;LPS组（L组）股静脉注射LPS 5mg/kg后机械通气4 h;地氟醚1.0MAC组（D1）和地氟醚1.5 MAC组（D2）组：股静脉注射LPS 5 mg/kg后机械通气,分别吸入地氟醚1.0 MAC和1.5 MAC 4 h,机械通气4 h后处死大鼠,测定肺组织超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量、一氧化氮（NO）含量、总一氧化氮合酶（tNOS）活性、诱导型一氧化氮合酶（iNOS）活性、iNOS mRNA和iNOS表达水平。结果与C组比较,L组SOD活性下降,MDA含量、NO含量、tNOS活性、iNOS活性、iNOS mRNA和iNOS表达升高（P〈0.01）;与L组比较,D1组上述各项指标差异无统计学意义（P〉0.05）,D2组SOD活性下降,MDA含量、iNOS活性、iNOS mRNA和iNOS表达升高（P〈0.05）;与D1组比较,D2组SOD活性下降,MDA含量、iNOS活性、iNOS mRNA和iNOS表达升高（P〈0.05）。结论吸入地氟醚1.5 MAC 4 h可加重LPS诱导大鼠肺组织氧化应激反应,吸入地氟醚1.0 MAC对其无影响。     

Penehyclidine hydrochloride ameliorates renal ischemia–reperfusion injury in rats

Background

Renal ischemia–reperfusion (I/R) injury is a major cause of acute kidney failure by mechanisms that involve oxidative stress, inflammation, and apoptosis. Penehyclidine hydrochloride (PHC), a selective anticholinergic agent, possesses anti-inflammatory, antioxidative stress, and antiapoptotic effects. Therefore, we investigated the ability of PHC to ameliorate renal I/R injury in Sprague–Dawley rats.

Materials and methods

Rats were randomly assigned to three groups (35 rats per group): sham operated, saline-treated I/R, and PHC-treated I/R. After removing the right kidney, renal I/R injury was induced by clamping the left renal artery for 45 min followed by reperfusion. The rats were administered PHC (0.45 mg/kg, intravenously) or saline 30 min before renal ischemia. The blood and kidneys were harvested at 1, 3, 6, 12, or 24 h after reperfusion. Renal function and histologic changes were assessed. Markers of oxidative stress, inflammation, and apoptosis in the kidneys were also measured.

Results

PHC treatment significantly attenuated renal dysfunction and histologic damage caused by I/R injury. The treatment also decreased malondialdehyde level and attenuated the reduction in superoxide dismutase activity in the kidney. Moreover, the levels of activated p38 mitogen-activated protein kinase, nuclear factor kappa B, and caspase 3 were lower in the PHC-treated animals.

Conclusions

PHC protected rat kidneys from I/R injury by attenuating oxidative stress, inflammatory response, and apoptosis. Thus, PHC may represent a novel practical strategy for the treatment of renal I/R injury.     

Oxidative stress in lung tissue induced by CO2 pneumoperitoneum in the rat

Background: Clinical trials have found that the pneumoperitoneum has potentially hazardous side effects. The biochemical basis of organ injury induced by pneumoperitoneum is, however, not well defined. Since oxidative stress is believed to play an important role in many pathological conditions, we set out to examine oxidative stress markers in the lung, liver, kidney, and pancreas by using a rat model of laparoscopy with CO₂ pneumoperitoneum and comparing it to a group with gasless laparoscopy. Methods: Malondialdehyde (for lipid peroxidation), protein-bound carbonyls (for protein oxidation), reduced and oxidized glutathione, and the neutrophil marker myeloperoxidase were evaluated in tissue homogenates at 2 h, 6 h, and 18 h after laparoscopy. Immunoblotting was used to analyze the modification of lung proteins by 4-hydroxynonenal at 6 h. Results: Significant lipid peroxidation was found selectively in lungs at 2 h and 6 h after CO₂ pneumoperitoneum. This was accompanied by a loss of glutathione but only minor protein oxidation. Further, lung proteins were clearly modified by the aldehydic product of lipid peroxidation 4-hydroxynonenal. Myeloperoxidase in lungs increased continuously up to 18 h in both experimental groups, but there were higher levels in the group with pneumoperitoneum. Conclusion: Oxidative stress is likely to contribute to the impairment of pulmonary function after laparoscopic operations using a CO₂ pneumoperitoneum. Received: 22 November 1999/Accepted: 22 March 2000/Online publication: 10 July 2000     

气腹性肺损伤的机制与防治策略

背景 腹腔镜手术具有创伤小、恢复快等特点.但手术过程中建立CO2气腹会造成腹腔内高压和酸碱平衡失调,引起不同程度的肺组织损伤,导致术后肺功能不全,严重者甚至可以发展为急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS). 目的 阐述气腹性肺损伤的机制和防治研究新进展. 内容 气腹性肺损伤的发生机制很复杂,可由通气/血流比例失调、氧化和抗氧化系统失衡、缺血/缺氧、缺血/再灌注损伤、促炎和抗炎反应失衡等因素引起.通过小潮气量联合呼气末正压通气的肺通气模式,允许性高碳酸血症,气腹前预处理和药物的应用可以减轻气腹引起的肺损伤. 趋向 通过对CO2气腹引起肺损伤的发生机制及防治策略进行综述,期望为气腹性肺损伤的预防及治疗提供新的思路.     

右美托咪定对经皮冠状动脉介入治疗患者氧化应激的影响

目的评价右美托咪定对经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)患者氧化应激的影响。方法选择急性心肌梗死需行急诊PCI患者50例,男39例,女11例,年龄47~79岁,体重45~83kg,ASAⅢ或Ⅳ级,采用随机数字表法将患者分为右美托咪定组(D组)和对照组(C组),每组25例。D组麻醉诱导前30min静脉泵注负荷剂量右美托咪定0.5μg/kg,泵注时间10min,随后持续静脉泵注右美托咪定0.2~1.0μg·kg~(-1)·h~(-1)至术毕;C组采用同样方法静脉泵注等量生理盐水。根据RASS镇静程度评估表,维持RASS评分-2~2分。于麻醉诱导前(T_0)、术毕(T_1)、术后6h(T_2)和24h(T_3)采集颈静脉血4ml,分别进行中性粒细胞(PMN)计数、血清丙二醛(MDA)浓度和超氧化物歧化酶(SOD)活性测定。记录术中低血压、心动过缓和低氧血症等不良反应的发生情况。结果与T_0时比较,T_1~T_3时两组血清PMN计数、MDA浓度均明显升高,血清SOD活性明显降低(P0.01或P0.05);T_1~T_3时D组PMN计数、MDA浓度均明显低于C组,血清SOD活性明显高于C组(P0.05)。两组患者术中低血压、心动过缓和低氧血症的发生率差异无统计学意义。结论持续静脉泵注右美托咪定0.5μg/kg,可以更好地抑制PCI患者的氧化应激反应,有助于减轻心肌缺血-再灌注损伤。     

ERK信号通路在右美托咪定减轻小鼠神经母细胞瘤细胞氧化应激损伤中的作用

目的观察右美托咪定对过氧化氢(H_2O_2)所致小鼠神经母细胞瘤细胞(mouse neuroblastoma N2acells,N2a)氧化应激损伤的影响,探讨ERK信号通路的作用。方法在N2a细胞培养基中加入一定浓度的H_2O_2建立N2a细胞氧化应激损伤模型。将细胞分为五组:对照组(C组)、右美托咪定组(D组)、H_2O_2组(H组)、H_2O_2+右美托咪定组(HD组)、H_2O_2+右美托咪定+ERK抑制剂组(HDP组)。H组、HD组和HDP组给予200μmol/L的H_2O_2,HD组在H_2O_2处理前30min加入100ng/ml右美托咪定,HDP组在H_2O_2处理前30 min加入100ng/ml右美托咪定和20μmol/LERK抑制剂PD98059,D组在相应时点加入100ng/ml右美托咪定,C组给予等容量生理盐水。在H_2O_2刺激1h,检测细胞上清SOD活性,并分析ERK磷酸化水平;H_2O_2刺激4h,观察细胞生存、细胞形态学变化。结果与C组比较,H组N2a细胞生存率明显降低,细胞形态明显损伤,SOD活性明显下降(P0.05);与H组比较,HD组的细胞生存率明显升高,细胞形态明显改善,SOD活性明显升高,ERK磷酸化水平明显增强(P0.05);与HD组比较,HDP组细胞生存率明显降低,细胞形态明显恶化,SOD活性明显降低(P0.05)。C组和D组细胞生存率、细胞形态、SOD活性及ERK磷酸化水平差异无统计学意义。结论右美托咪定预处理能够减轻H_2O_2所致的N2a细胞氧化应激损伤,其机制可能是通过激活细胞内ERK信号通路和提高SOD活性。     

Myocardial protection with and without leukocyte depletion: a comparative study on the oxidative stress

We tested the hypothesis that controlled reperfusion with leukocyte-depleted blood could improve myocardial protection by reducing the oxidative stress in patients undergoing myocardial revascularization. Thirty-four patients receiving antegrade/retrograde blood cardioplegia were divided into: group A: 11 patients with ejection fractions (EF) less than 35%, treated with leukocyte-depleted controlled blood reperfusion, group B: 11 patients with EF less than 35% in whom no leukocyte depletion was performed, group C: 6 patients with EF more than 45% treated as group A and group D: 6 patients with EF more than 45% without leukocyte depletion. To asses the oxidative stress, we evaluated total, total oxidized (GSSX), and reduced glutathione (GSH) in coronary sinus plasma, immediately before cross-clamping the aorta (T0), and at 0 (T1), 15 (T2) and 30 (T3) min after unclamping it. In groups A and B a significant shift towards oxidation of redox status of glutathione (GSH/GSSX) at T1 vs T0 was observed. Glutathione redox ratio remained low in group B while in group A it returned to the basal value at T2 with a significant difference from group B at T2 and T3. No differences were observed between groups C and D. In conclusion, our data show that leukocyte-depleted reperfusion can afford a better myocardial protection in patients with left ventricular dysfunction, while it seems unnecessary in patients with normal EF.     

七氟醚后处理对体外循环下心脏瓣膜置换术患者心肌氧化应激损伤的影响

目的 探讨七氟醚后处理对体外循环下心脏瓣膜置换术患者心肌氧化应激损伤的影响.方法 拟在体外循环下行心脏瓣膜置换术的风湿性心脏病患者30例,年龄30～59岁,体重42～62 kg,射血分数＞55%,ASA分级Ⅱ或Ⅲ级,NYHA心功能分级Ⅱ或Ⅲ级,采用随机数字表法,将患者随机分为对照组(C组)和七氟醚后处理组(S组),每组15例.S组于主动脉开放即刻经体外循环机给予2%七氟醚15 min,C组不做此项处理.于切皮前即刻(T1)、主动脉开放后30 min(T2)、3 h(T3)和24 h(T4)时取颈内静脉血样,检测血浆MDA浓度.于术前和停机后取左心耳组织,采用Western blot法测定α-谷胱甘肽-S-转移酶(α-GST)的表达.结果 与C组比较,S组T2,3时血浆MDA浓度降低,停机后心肌组织α-GST表达上调(P＜0.05).结论 七氟醚后处理可增强体外循环下心脏瓣膜置换术患者抗氧化能力,减轻心肌氧化应激损伤,该作用有助于减轻心肌再灌注损伤.

Abstract：

Objective To investigate the effect of sevoflurane postconditioning on the myocardial oxidative stress injury in patients undergoing heart valve replacement with cardiopulmonary bypass (CPB) . Methods Thirty ASA Ⅱ or Ⅲ and NYHA class Ⅱ or ID patients, aged 30-59 yr, weighing 42-62 kg, scheduled for cardiac valve replacement with CPB, were randomly divided into 2 groups ( n = 15 each) : control group (group C) and sevoflurane postconditioning group (group S) . Anesthesia was induced with iv injection of midazolam 0.05-0.08 mg/kg, fentanyl 3-6 μg/kg, vecuronium 0.10-0.15 mg/kg and etomidate 0.1-0.2 mg/kg. The patients were tracheal intu- bated and mechanically ventilated. Anesthesia was maintained with intermittent iv boluses of fentanyl and midazolam and continuous infusion of atracurium and propofol. In group S, 2% sevoflurane was given over 15 min via the cardiopulmonary bypass machine immediately after aortic unclamping. Blood samples from the internal jugular vein were collected immediately before skin incision (T1 ) and at 30 min, 3 h and 24 h after aortic unclamping (T2-4 ) for measurement of the plasma malondialdehyde level. Myocardial tissues were taken from the left auricle before operation and after termination of CPB for determination of α-glutathione-S-transferase expression by Western blot. Results The plasma malondialdehyde concentration was significantly lower at T2, 3, while a-glutathione-S-transferase expression in myocardial tissues higher after termination of CPB in group S than in group C ( P ＜ 0.05) . Conclusion Sevoflurane postconditioning can enhance the antioxidant capacity and attenuate the myocardial oxidative stress injury in patients undergoing cardiac valve replacement with CPB, which may be helpful to reduce myocardial ischemia-reperfusion injury.     

七氟醚后处理对大鼠局灶性脑缺血再灌注时氧化应激反应的影响

目的 探讨七氟醚后处理对大鼠局灶性脑缺血再灌注时氧化应激反应的影响.方法 健康雄性Wistar大鼠24只,体重240 ～ 280 g,采用随机数字表法,将大鼠随机分为3组(n=8):假手术组(S组)、局灶性脑缺血再灌注组(I/R组)和七氟醚后处理组(SP组).采用大脑中动脉阻断法制备局灶性脑缺血再灌注模型.SP组于再灌注前20 min至再灌注后10 min吸入3.9％(1.5 MAC)七氟醚.再灌注24 h时取脑组织,测定丙二醛(MDA)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)和谷胱甘肽还原酶(GR)水平,观察脑组织病理学结构;TTC染色法测定脑梗死体积.结果 与S组相比,I/R组和SP组脑梗死体积增加,MDA水平升高,I/R组GSH、SOD、CAT、GSH-Px和GR水平降低,SP组GSH-Px水平降低(P＜0.05);与I/R组相比,SP组MDA水平降低,脑梗死体积减小,GSH、SOD、CAT、GSH-Px和GR水平升高(P＜0.05).SP组脑组织病理学损伤较I/R组减轻.结论 七氟醚后处理减轻大鼠局灶性脑缺血再灌注损伤的机制与增强抗氧化酶活性,抑制氧化应激反应有关.     

Reduction of renal ischemia reperfusion injury by hydrogen sulfide preconditioning through inhibiting oxidative stress

Objective To investigate the possible role of oxidative stress in the protection of hydrogen sulfide during renal ischemia reperfusion. Methods Male Wistar rats were randomly divided into 3 groups: sham operation (Sham) group, renal ischemia reperfusion (IR) group subject to occlusion of left renal pedicle for 45 min then reperfusion for 24 h, and sodium hydrosulfide (NaHS) preconditioning group with continuous infusion of NaHS (450 nmol/min) by left renal artery for 10 min before ischemia reperfusion. Renal injuries were evaluated by PAS staining. The protein levels of NADPH oxidase (NOX) 4, NOX2 were analyzed by Western blotting. The reactive oxygen species (ROS) level of renal tissue was determined by dihydroethidium (DHE) staining assay. Renal superoxide dismutase (SOD), malonic dialdehyde (MDA) and Scr, BUN were evaluated by chromatometry assay. Cell apoptosis were evaluated by TdT-mediated dUTP nick end labeling (TUNEL) staining. Results Compared with Sham group, in IR group the renal NOX4 and NOX2 protein expressions, the existence of acute tubular necrosis and ROS expression were up-regulated (all P＜0.01); MDA, Scr, and BUN were increased and SOD was decreased significantly in IR-treated kidney (all P＜0.01); Moreover, more apoptotic cells presented in the risk zone of IR-treated kindey (P＜0.01). The effects induced by IR were inhibited by NaHS. Compared to that in IR group, NaHS precondition reversed IR-induced damages of renal function and renal tissue, increased SOD activity and decreased MDA expression (all P＜0.05), as well as reduced the expression of NOX4, NOX2 and ROS (all P＜0.05). Moreover, NaHS precondition reduced apoptosis after IR (P＜0.05). Conclusions NaHS alleviates renal ischemia reperfusion injury through inhibiting oxidative stress. Hydrogen sulfide can decrease ROS by inhibiting the activation of NOX, further inhibit the activation of NOD-like receptor, and alleviate kidney damage.     

家兔CO2气腹时胰岛素抵抗的发生

目的 评价家兔CO2气腹时胰岛素抵抗的发生.方法 雄性家兔10只,随机分为2组(n=5),对照组和实验组CO2气腹压力分别为0、15 mm Hg,时间1 h.于气腹前、气腹30、60 min、气腹后4、24 h测定血浆葡萄糖、胰岛素、肿瘤坏死因子-α(TNF-α)水平及红细胞的胰岛素高亲和力受体、低亲和力受体的亲和常数和结合位点数,计算胰岛素敏感指数.结果 与对照组比较,实验组气腹中及气腹后血浆葡萄糖、胰岛素和TNF-α水平均升高,气腹后胰岛素敏感指数降低(P＜0.05或0.01),气腹中及气腹后红细胞的胰岛素高亲和力受体、低亲和力受体的亲和常数和结合位点数差异无统计学意义(P＞0.05).结论 15 mm Hg CO2气腹1 h可引起家兔血浆葡萄糖和胰岛素水平升高,胰岛素敏感性降低,发生了胰岛素抵抗.     

虎杖苷对脓毒症急性肾损伤大鼠炎症反应和氧化应激的影响

目的观察虎杖苷在脓毒症急性肾损伤(acute kidney injury,AKI)大鼠中的抗炎和抗氧化应激作用。方法 SD大鼠72只,体重180~220g,随机分为四组:假手术对照组(Sham组);盲肠结扎穿刺术(CLP)+生理盐水组(CN组);CLP+溶媒组(CV组);CLP+虎杖苷组(CD组),每组18只。对CN、CV和CD组大鼠施行CLP,模拟脓毒症AKI动物模型,Sham组大鼠盲肠既不被结扎也不被穿孔,余步骤则与CLP组相同,未行其他任何处理。CLP术后6、12、18h,CN、CV和CD组经大鼠尾静脉分别注射生理盐水、溶媒、虎杖苷30 mg/kg。在CLP术后24h记录血清肌酐(Cr)和尿素氮(BUN)等肾功能指标,观察肾脏组织病理形态改变并进行肾小管损伤评分,检测血清TNF-α、IL-1β和IL-6浓度,测定肾组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)、谷胱甘肽(GSH)浓度。结果与Sham组比较,CN组和CV组血清Cr、BUN、TNF-α、IL-1β和IL-6浓度、肾小管损伤评分和肾组织MDA浓度明显升高(P0.01),肾组织SOD活性、GSH浓度明显降低(P0.01)。与CN组和CV组比较,CD组血清Cr、BUN、IL-1β和IL-6浓度、肾小管损伤评分和肾组织MDA浓度明显降低(P0.05),肾组织SOD活性、GSH浓度明显升高(P0.05)。结论盲肠结扎穿刺术导致的脓毒症可引起急性肾损伤,虎杖苷可通过显著的抗炎和抗氧化应激作用,减轻肾组织损伤,改善肾功能。     

Bosentan reduces oxidative burst in acid aspiration-induced lung injury in rats

Background

Acid aspiration induces lung injury by causing an intense inflammatory reaction. Neutrophils are attracted by various cytokines, such as TNFβ, and release reactive oxygen species, which then cause acute lung injury. Endothelin antagonists, such as bosentan, have been found to possess anti-inflammatory properties.

Materials and methods

We performed a prospective, randomised, controlled study to evaluate the effects of bosentan in a rat model of acid-induced lung injury. Sprague-Dawley rats underwent sevoflurane anaesthesia; lung injury was then induced by instillation of 1.2 mL/kg, 0.1 M hydrochloric acid. The lungs were ventilated for 6 h and then randomised into three groups: bosentan 30 mg/kg body weight, 90 mg/kg body weight or sodium chloride, each applied immediately after acid aspiration via a gastric tube.

Results

After induction of acute lung inflammation, the production of reactive oxygen species by PMN following stimulation with FMLP increased significantly. Comparison of pre-treatment and post-treatment in the 90 mg/kg bosentan treatment group did not show a significant increase of reactive oxygen species following stimulation with FMLP. A comparison of the absolute difference of the MESF demonstrated a significant difference between the control group and the group treated with 90 mg/kg bosentan.

Conclusions

Bosentan administration at 90 mg/kg body weight reduced the release of reactive oxygen species after 360 min in acid aspiration-induced lung injury in rats.     

N-乙酰半胱氨酸对CO2气腹导致急性肾损伤的预防作用

目的探讨N-乙酰半胱氨酸（NAC）对CO2气腹所引起的肾功能损害的保护作用。方法42只成年Wistar大鼠被分为7组,每组6只。组1-4未经NAC处理,其中组1为无气腹对照,组2为1h气腹后24h评估,组3为3h气腹后24h评估,组4为3h气腹后72h评估;组5～7于气腹前2d开始服用NAC直至评估前,其中组5为无气腹对照,组6组为3h气腹后24h评估,组4为3h气腹后72h评估。通过菊粉清除试验检测肾小球滤过率;采用硫代巴比妥酸法（TBARS）评估肾脏氧化应激程度。结果短时间（1h）气腹对肾小球滤过率和血清TBARS无明显影响（组2比组1,P〉0．05）;而长时间（3h）气腹会导致肾小球滤过率明显降低,血清TBARS明显升高（组3和组4比组1,均P〈0．05）。而服用NAC后,长时间（3h）气腹则不再会导致肾小球滤过率的降低和血清TBARS的升高（组6和组7比组5,均P〉0．05）。结论NAC可有效预防因长时间气腹通过诱发氧化应激所导致的肾功能损害。     

Dexamethasone pretreatment alleviates intestinal ischemia–reperfusion injury

Background

Activated mast cells are involved in the pathogenesis of intestinal ischemia–reperfusion (I/R)-related injury. Dexamethasone has been widely used to protect organs from I/R injury. This study was conducted to investigate the impact of treatment with dexamethasone at different stages of the II/R process on mast cell infiltration and activity and intestinal injury.

Methods

Kunming mice were randomized and subjected to a sham surgery or the II/R induction by clamping the superior mesenteric artery for 30 min and then reperfusion. During the II/R induction, the mice were treated intravenously with dexamethasone (10 mg/kg) for 30 min before ischemia (pretreatment group), at 5 min after clamping the superior mesenteric artery (isc-treatment group), or at the beginning of perfusion (rep-treatment group), respectively. The levels of intestinal injury, mast cell infiltration and activity, tumor necrosis factor α (TNFα) and myeloperoxidase (MPO) activity in the intestines, and mouse survival rates were measured.

Results

The death rates, levels of intestinal injury, mast cell infiltration and activity, and tumor necrosis factor α and myeloperoxidase activity in the intestinal tissues from the II/R group were similar to those from the isc-treatment and rep-treatment groups of mice and were significantly higher than those from the sham group. In contrast, pretreatment with dexamethasone significantly mitigated the II/R-induced mast cell infiltration and activity, inflammation, and intestinal injury and reduced the death rates in mice.

Conclusions

Pretreatment with dexamethasone inhibits II/R injury by reducing mast cell–related inflammation in mice.