Renal effects of three endoaortic occlusion strategies in a swine model of hemorrhagic shock

IntroductionTrauma patients are predisposed to kidney injury. We hypothesized that in shock, zone 3 REBOA would increase renal blood flow (RBF) compared to control and that a period of zone 3 occlusion following zone 1 occlusion would improve renal function compared to zone 1 occlusion alone.Materials and methodsTwenty-four anesthetized swine underwent hemorrhagic shock, 45 min of zone 1 REBOA (Z1, supraceliac), zone 3 REBOA (Z3, infrarenal), or no intervention (control) followed by resuscitation with shed blood and 5 h of critical care. In a fourth group (Z1Z3), animals underwent 55 min of zone 3 REBOA following zone 1 occlusion. Physiologic parameters were recorded, blood and urine were collected at specified intervals.ResultsDuring critical care, there were no differences in RBF between the Z1 and Z3 groups. The average RBF during critical care in Z1Z3 was significantly lower than in Z3 alone (98.2 ± 23.9 and 191.9 ± 23.7 mL/min; p = 0.046) and not different than Z1. There was no difference in urinary neutrophil gelatinase-associated lipocalin-to-urinary creatinine ratio between Z1 and Z1Z3. Animals in the Z1Z3 group had a significant increase in the ratio at the end of the experiment compared to baseline [median (IQR)] [9.2 (8.2–13.2) versus 264.5 (73.6–1174.6)]. Following Z1 balloon deflation, RBF required 45 min to return to baseline.ConclusionNeither zone 3 REBOA alone nor zone 3 REBOA following zone 1 REBOA improved renal blood flow or function. Following zone 1 occlusion, RBF is restored to baseline levels after approximately 45 min.     

黄芪甲苷对大鼠肺缺血再灌注后氧化应激损伤的影响

目的：研究黄芪甲苷对大鼠肺缺血再灌注损伤后氧化应激的影响。方法将50只实验用大鼠随机分为假手术组、模型组和黄芪甲苷(20、40、80 mg/kg)组,每组10只。采用夹闭左肺门45 min后松夹的方法制备肺缺血再灌注损伤大鼠模型,各组分别于术前30 min腹腔注射给药。再灌注2h后,测定各组大鼠肺组织湿/干重比,测定肺组织中抗氧化酶(超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶)活性,测定血清中总抗氧化能力、髓过氧化物酶活性和丙二醛含量,通过HE染色法观察肺组织形态结构变化,TUNEL 法观察肺组织细胞凋亡状况并计算凋亡指数,采用Western blot法测定肺组织中核转录因子κB蛋白表达并进行半定量分析。结果与模型组比较,黄芪甲苷(40、80 mg/kg)组大鼠肺组织湿/干重比显著降低,肺组织中超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶活性显著升高,血清中总抗氧化能力升高,髓过氧化物酶活性、丙二醛含量降低,肺组织形态结构变化和肺细胞病变显著减轻,肺细胞凋亡状况明显改善,肺细胞凋亡指数降低,肺组织中核转录因子κB蛋白表达量降低,差异均有统计学意义(P<0.05或P<0.01)。结论黄芪甲苷具有抑制肺缺血再灌注损伤大鼠氧化应激的作用,作用机制可能与黄芪甲苷能够改善肺组织和血清中抗氧化酶活性、提高氧自由基清除能力以及下调核转录因子κB蛋白表达、抑制肺细胞凋亡有关。     

大鼠脑缺血后脑内MPO、NSE活性变化

目的 通过测定大鼠局灶性脑缺血-再灌流后不同时点脑组织中髓过氧化物酶(MPO)和神经元特异性烯醇化酶(NSE)活性的变化,探讨炎症反应与脑缺血损伤的关系.方法 用线栓法制备大鼠左侧大脑中动脉缺血-再灌流模型,检测缺血3h再灌流后6h、12h、24h、48h、72h和7d脑组织中MPO和NSE活性、脑梗死体积的变化.结果 缺血组脑组织中NSE和MPO活性升高,再灌流后48h的NSE为(5.44±0.95)ng/ml,MPO为4.49±0.22;72h分别为(5.36±0.65)ng/l和5.96±0.19,升高最为明显.脑梗死体积随再灌流时间延长而增加,第7d梗死体积百分比为(39.18±0.63)%.局灶性缺血脑组织中MPO活性与组织损伤(NSE活性)间具有高度正相关性.结论 炎症反应是加重脑缺血损伤的重要因素.     

Non-coding RNAs as therapeutic targets for preventing myocardial ischemia-reperfusion injury

Introduction: New treatments are required to improve clinical outcomes in patients with acute myocardial infarction (AMI), for reduction of myocardial infarct (MI) size and preventing heart failure. Following AMI, acute ischemia/reperfusion injury (IRI) ensues, resulting in cardiomyocyte death and impaired cardiac function. Emerging studies have implicated a fundamental role for non-coding RNAs (microRNAs [miRNA], and more recently long non-coding RNAs [lncRNA]) in the setting of acute myocardial IRI.

Areas covered: In this article, we discuss the roles of miRNAs and lncRNAs as potential biomarkers and therapeutic targets for the detection and treatment of AMI, review their roles as mediators and effectors of cardioprotection, particularly in the settings of interventions such as ischemic pre- and post-conditioning (IPC & IPost) as well as remote ischemic conditioning (RIC), and highlight future strategies for targeting ncRNAs to reduce MI size and prevent heart failure following AMI.

Expert opinion: Investigating the roles of miRNAs and lncRNAs in the setting of AMI has provided new insights into the pathophysiology underlying acute myocardial IRI, and has identified novel biomarkers and therapeutic targets for detecting and treating AMI. Pharmacological and genetic manipulation of these ncRNAs has the therapeutic potential to improve clinical outcomes in AMI patients.     

瑞舒伐他汀预处理对缺血再灌注大鼠大脑中动脉血管平滑肌细胞炎症因子的影响及其机制

目的 探讨瑞舒伐他汀预处理对大鼠局灶性脑缺血再灌注后大脑中动脉血管平滑肌细胞（VSMCs）中炎性细胞因子白细胞介素（IL）-1β、IL-6、肿瘤坏死因子ɑ（TNF-α）表达的影响以及可能的机制。 方法 36只健康成年SD大鼠,雌雄不限,随机分为假手术组,局灶性脑缺血再灌注组,瑞舒伐他汀预处理组,每组12只。大脑中动脉缺血2 h再灌注24 h后, Real-time PCR及Western blotting法检测大鼠大脑中动脉VSMCs中IL-1β、IL-6和TNF-α以及核因子κB（NF-κB）mRNA和蛋白的表达。 结果 再灌注24 h后,模型组VSMCs IL-1β、IL-6 以及TNF-αmRNA和蛋白的表达明显增加,而给予瑞舒伐他汀预处理后,可明显抑制大脑中动脉VSMCs中IL-1β、IL-6和TNF-α mRNA和蛋白的高表达,同时也可发现,VSMCs中NF-κB mRNA和蛋白的表达也明显减少。 结论 瑞舒伐他汀预处理可有效抑制大脑中动脉VSMCs中IL-1β、IL-6和TNF-α mRNA和蛋白的表达,从而减轻缺血再灌注后炎症反应对脑组织的进一步损伤作用。瑞舒伐他汀预处理对IL-1β、IL-6及TNF-α的作用可能与其减少VSMCs中NF-κB的表达有关。     

Milrinone-induced postconditioning reduces hepatic ischemia-reperfusion injury in rats: the roles of phosphatidylinositol 3-kinase and nitric oxide

Background

Ischemic postconditioning (PostC) protects the liver against ischemia-reperfusion (IR) injury. Milrinone, a phosphodiesterase 3 inhibitor, has been reported to exhibit preconditioning properties against hepatic IR injury; however, its PostC properties remain unknown. This study investigated whether milrinone has PostC properties against hepatic IR injury and the roles of phosphatidylinositol 3-kinase (PI3K) and nitric oxide synthase (NOS).

Materials and methods

Male Wistar rats were separated into six groups: (1) group S: animals that underwent sham operation without ischemia, (2) group C: ischemia followed by reperfusion with no other intervention, (3) group M: milrinone administered immediately after reperfusion, (4) group MW: wortmannin, a PI3K inhibitor, injected before milrinone administration, (5) group MN: l-NAME, a NOS inhibitor, injected before milrinone administration, and (6) group MD, milrinone administered 30 min after reperfusion. Except for group S, all groups underwent 1 h of warm ischemia of median and left lateral lobes, followed by 5 h of reperfusion. Biochemical liver function analysis and histologic examination were performed.

Results

Serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels, histologic damage scores, and apoptotic rate in group M were significantly lower than those in group C. The inhibition of PI3K or NOS prevented this protective effect. Milrinone administered 30 min after reperfusion did not show obvious protective effects.

Conclusions

Milrinone-induced PostC protects against hepatic IR injury when it is administered immediately after reperfusion, and PI3K and NOS may play an important role in this protective effect.     

The effects of iloprost on ischemia-reperfusion injury in skeletal muscles in a rodent model

Purpose

The aim of this study was to investigate the effects of iloprost (IL) on ischemia-reperfusion injury in a rodent model.

Materials and methods

Twenty-four Wistar Albino rats were randomized into four groups (n = 6). Laparotomy was performed in all groups under general anesthesia. Only laparotomy was applied in group S (Sham). Ischemia-reperfusion group (group I/R) underwent ischemia and reperfusion performed by clamping and declamping of the infrarenal abdominal aorta for 120 min. The iloprost group (group IL) received intravenous infusion of IL 0.5 ng/kg/min, without I/R. Group I/R + IL received intravenous infusion of IL 0.5 ng/kg/min immediately after 2 h period of ischemia. At the end of the reperfusion period, all rats were killed under anesthesia and skeletal muscle samples of lower extremity were harvested for biochemical and histopathologic analyses.

Results

Tissue levels of endothelial nitric oxide were significantly higher in I/R groups than those in groups S and IL. The heat shock protein 60 levels were higher in group I/R than the other groups. But the heat shock protein 60 levels in group I/R + IL were found to be similar with the groups S and IL. Malondialdehyde levels were significantly higher in group I/R. On the other hand, in group I/R + IL, malondialdehyde levels were higher than those in groups S and IL but lower than those in group I/R. Superoxide dismutase (SOD) enzyme activities were found to be significantly lower in group I/R than the other groups. Also in group I/R/I, the SOD enzyme activities were higher than those in group I/R. But, in group I/R + IL, SOD levels were found to be higher than those in group I/R but lower than those in groups S and IL.

Conclusions

These results indicate that IL has protective effects on I/R injury in skeletal muscle in a rodent model.     

1,6-二磷酸果糖对肝脏冷缺血-再灌注时肺的保护作用

目的评价1,6-二磷酸果糖(FDP)对大鼠肝脏冷缺血-再灌注时肺的保护作用。方法健康雄性SD大鼠24只,周龄8～10周,体重200～250g,采用随机数字表法将其分为三组,每组8只。O组大鼠仅进行单纯开关腹手术,游离相应血管;K组大鼠采用肝脏冷缺血-再灌注模型手术,不给予任何干预措施;F组大鼠采用肝脏冷缺血-再灌注模型,在切皮时经睾丸静脉给予FDP 250mg/kg。于再灌注后6h收集血清和肺组织标本,利用ELISA和免疫组化检测TNF-α和IL-6表达水平;测定肺组织MDA和SOD含量,光镜下观察肺组织病理学结果。结果与O组比较,K组和F组大鼠血清TNF-α和IL-6浓度及肺组织MDA含量均明显升高(P0.05),肺组织SOD含量明显降低(P0.05);与K组比较,F组血清TNF-α和IL-6浓度及肺组织MDA的含量均明显降低(P0.05),肺组织SOD含量均明显升高(P0.05)。免疫组化染色显示O组TNF-α和IL-6表达较K组和F组明显降低,与K组比较,F组TNF-α和IL-6的表达明显降低。O组肺组织形态结构未见明显异常,K组肺泡腔内渗出明显,大量的炎症细胞浸润,F组肺组织损伤较K组减轻。结论 1,6-二磷酸果糖可明显减轻大鼠肝脏冷缺血-再灌注后的急性肺损伤。     

血塞通预处理对心肌缺血再灌注损伤的早期保护作用

目的观察血塞通预处理对大鼠心肌缺血再灌注(I/R)损伤的早期保护作用,并研究其可能机制.方法采用开胸冠状动脉结扎建立缺血再灌注模型,25只雄性SD大鼠随机分为假手术组,缺血再灌注组(I/R组),缺血预处理组(IPC组),血塞通预处理组(PNS预处理组).再灌注后2 h测定各组血清肌酸磷酸激酶-MB(CK-MB)含量以及心肌细胞凋亡情况和心肌细胞Bcl-2和Bax蛋白的表达,并观察心肌超微结构变化.结果IPC组及PNS预处理组血清CK-MB均明显低于I/R组(P＜0.05).IPC组及PNS预处理组TUNEL阳性细胞数,Bax阳性细胞数均明显低于I/R组(P＜0.05).和I/R组相比,IPC组及PNS预处理组心肌超微结构损伤减轻.结论PNS预处理后心肌细胞凋亡减少,心肌细胞损伤减轻,对I/R损伤产生有和缺血预处理类似的早期保护作用.     

七氟醚后处理对糖尿病大鼠脑缺血-再灌注损伤的影响

目的研究七氟醚后处理对糖尿病大鼠脑缺血-再灌注损伤的影响。方法雄性SD大鼠32只,3.0~3.5月龄,体重280~320 g,采用随机数字表法分为四组:非糖尿病缺血-再灌注对照组(NDC组)、糖尿病缺血-再灌注对照组(DC组)、非糖尿病缺血-再灌注七氟醚后处理组(NDS组)和糖尿病缺血-再灌注七氟醚后处理组(DS组),每组8只。采用栓线法和链脲佐霉素制备缺血-再灌注损伤大鼠模型和糖尿病大鼠模型。缺血2 h,再灌注24 h后,进行大鼠神经缺损评分,采用TTC法测定脑梗死体积,Western blot法测定血管生成素-1(angiopoiettin-1,Ang-1)蛋白含量。结果DC组神经缺损评分、脑梗死体积百分比明显高于NDC组,Ang-1蛋白含量明显低于NDC组(P0.05);NDS组神经缺损评分、脑梗死体积百分比明显低于NDC组,Ang-1蛋白含量明显高于NDC组(P0.05);DS组神经缺损评分、脑梗死体积百分比明显低于DC组,Ang-1蛋白含量明显高于DC组(P0.05)。结论大鼠脑缺血-再灌注后,糖尿病可加重神经缺损,增大脑梗死体积,减少Ang-1蛋白含量;七氟醚可减轻神经缺损,减小脑梗死体积,增加Ang-1蛋白含量;七氟醚后处理减轻大鼠脑缺血-再灌注损伤与Ang-1蛋白含量增加有关。