H_2S Protecting against Lung Injury following Limb Ischemia-reperfusion by Alleviating Inflammation and Water Transport Abnormality in Rats

Objective To investigate the effect of H2S on lower limb ischemia-reperfusion （LIR） induced lung injury and explore the underlying mechanism. Methods Wistar rats were randomly divided into control group, IR group, IR＋ Sodium Hydrosulphide （NariS） group and IR＋ DL-propargylglycine （PPG） group. IR group as lung injury model induced by LIR were given 4 h reperfusion following 4 h ischemia of bilateral hindlimbs with rubber bands. NariS （0.78 mg/kg） as exogenous H2S donor and PPG （60 mg/kg） which can suppress endogenous H2S production were administrated before LIR, respectively. The lungs were removed for histologic analysis, the determination of wet-to-dry weight ratios and the measurement of mRNA and protein levels of aquaporin-1 （AQP1）, aquaporin-5 （AQP5） as indexes of water transport abnormality, and mRNA and protein levels of Toll-like receptor 4 （TLR4）, myeloid differentiation primary-response gene 88 （MyD88） and p-NF-KB as indexes of inflammation. Results LIR induced lung injury was accompanied with upregulation of TLR4-Myd88-NF-κB pathway and downregulation of AQP1/AQP5. NariS pre-treatment reduced lung injury with increasing AQP1/AQP5 expression and inhibition of TLR4-Myd88-NF-KB pathway, but PPG adjusted AO.PJAO.Ps and TLR4 pathway to the opposite side and exacerbated lung injury. Conclusion Endogenous H2S, TLR4-Myd88-NF-κB pathway and AQP1/AQP5 were involved in LIR induced lung injury. Increased H2S would alleviate lung injury and the effect is at least partially depend on the adjustment of TLR4-Myd88-NF-κB pathway and AQP1/AQP5 expression to reduce inflammatory reaction and lessen pulmonary edema.

Oxidative stress and hypoxia-induced factor 1α expression in gastric ischemia

AIM:To investigate the relation of reactive oxygen species (ROS) to hypoxia induced factor 1α (HIF-1α) in gastric ischemia. METHODS:The animal model of gastric ischemia reperfusion was established by placing an elastic rubber band on the proximal part of the bilateral lower limb for ligature for 3 h and reperfusion for 0,1,3,6,12 or 24 h. Ischemic post-conditioning,three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were conducted before reperfusion. Histological and immunohistochemical methods were used to assess the gastric oxidative damage and the expression of HIF1-α in gastric ischemia. The malondialdehyde (MDA) content and superoxide dismutase (SOD),xanthine oxidase (XOD) and myeloperoxidase (MPO) activities were determined by colorimetric assays. RESULTS:Ischemic post-conditioning can reduce post-ischemic oxidative stress and the expression of HIF-1α of gastric tissue resulting from limb ischemia reperfusion injury. MDA,SOD,XOD and MPO were regarded as indexes for mucosal injuries from ROS,and ROS was found to affect the expression of HIF-1α under gastric ischemic conditions. CONCLUSION:ROS affects HIF-1α expression under gastric ischemic conditions induced by limb ischemia reperfusion injury. Therefore,ROS can regulate HIF-1α expression in gastric ischemia.

Ischemic preconditioning produces more powerful anti- inflammatory and cardioprotective effects than limb remote ischemic postconditioning in rats with myocardial ischemia-reperfusion injury

Background Both ischemic preconditioning （IPC） and limb remote ischemic postconditioning （LRIPOC） have been shown to possess significantly different cardioprotective effects against the myocardial ischemia reperfusion injury （IRI）, but no study has compared the anti-inflammatory effects of IPC and LRIPOC during myocardial IRI process. We hypothesized that IPC and LRIPOC would produce different anti-inflammatory effects in an in vivo rat model with myocardial IRI.

Mechanism of the protective effects of noninvasive limbs preconditioning on myocardial ischemia-reperfusion injury

Background This study aimed at assessing the effect of noninvasive limb preconditioning on myocardial infarct size, and determining whether nitric oxide and neurogenic pathway play an important role in the mechanism of acute remote ischemic preconditioning （IPC）.Methods Forty Wistar rats were randomly divided into four experimental groups. In Group I , the rats underwent 30-minute occlusion of the left anterior descending coronary artery, and 120-minute reperfusion. In Group PL, the rats underwent four cycles of 5-minute occlusion and reperfusion of both hind limbs using a tourniquet before the experiment was continued as in Group I. In Group PL-N and Group PL-,, we administered L-nitro-arginine methyl ester （L-NAME） 10 mg/kg or hexamethonium chloride 20 mg,/kg intravenously, 10 minutes before IPC. Infarct size as a percentage of the area at risk was determined by triphenyhetrazolium chloride staining.Results There were no statistically significant differences in mean arterial pressure and heart rate among these groups at any time point during the experiment （ P〉0. 05 ）. The myocardial infarct size （IS） was decreased significantly in Group PL and Group PL-U compared with Group I , and the IS/AAR was 34. 5%± 7.6%, 35.9%±8.6% and58.5%±8.5%, respectively （P〈0.05）. The IS/AAR was 49.1%±6.5% in Group PEN, and there was no significant difference compared with Group I （P〉0. 05 ）.Conclusions Noninvasive limb IPC is effective in protecting the myocardium from ischemia reperfusion injury. Nitric oxide plays an important role in the mechanism of acute remote IPC, in which the neurogenic pathway is not involved.

Comparative study of the effect of basic fibroblast growth factor and vascular endothelial growth factor on limb ischemia/reperfusion injury of rats

Objective To investigate the effect of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) on limb ischemia/reperfusion injury of rats and the mechanism Methods The hind limb ischemia/reperfusion injury of male SD rats was induced by tourniquet for 2 hours and then reperfusing for 12 hours with administration of different agents Animals were divided into control, bFGF 10 and bFGF 50, VEGF 10 and VEGF 50 group by infusing physiological saline, 10 and 50?μg/kg bFGE, 10 and 50?μg/kg VEGF, respectively Blood was collected to determine malonyldialdehyde (MDA), and the ischemic reperfused gastrocnemius muscle and the contralateral control one were harvested together for measurement of tissue viability, water content, myeloperoxidose (MPO) activity, ATP and MDA concentration Results Compared with control group, tissue viability of ischemia/reperfusion limb in bFGF 10 and bFGF 50 group increased by 16 0% ( P <0 05) and 32 8% ( P <0 01), ATP content increased by 14 8% and 35 6% ( P <0 01), and plasma MDA level decreased by 45 2% and 56 2% ( P <0 01) 10?μg/kg bFGF had no significant effect on tissue water content, MPO activity, MDA concentration of ischemia/reperfusion limb, while 50?μg/kg of bFGF lowered these values by 15 7%, 32 5% and 13 6% ( P <0 05) and 14 7% ( P <0 01), MPO activity augmented by 44 9% and 96 1% ( P <0 01), ATP content decreased by 13 1% ( P <0 05) and 33 3% ( P <0 01) Plasma and tissue MDA concentrations in VEGF 10 group had no significant changes ( P >0 05), while in VEGF 50 group, these values were elevated by 46 4% and 38 6% ( P <0 01) Conclusion bFGF attenuated, while VEGF exacerbated ischemia/reperfusion injury of rat limb significantly, the mechanism of which was probably related to preventing or enhancing lipid peroxide, and increasing or decreasing energy store

3-硝基-N-甲基水杨酰胺对肢体缺血再灌注损伤大鼠骨骼肌的保护作用及机制

背景:线粒体活性氧爆发已被证明在骨骼肌缺血再灌注中起着关键作用。3-硝基-N-甲基水杨酰胺(3-nitro-N-methyl salicylamide,3-NNMS)可以有效降低电子传递速度,对肢体缺血再灌注损伤具有潜在的保护作用,但目前尚无明确的研究和临床应用。目的:探讨3-NNMS对肢体缺血再灌注损伤大鼠骨骼肌的保护作用及机制。方法:40只健康8周龄SD大鼠随机分为对照组及3-NNMS的0μg/mL组、25μg/mL组、125μg/mL组,每组10只。除对照组外,其余各组制备肢体缺血再灌注损伤大鼠模型,于再灌注前30 min,向损伤部位注射相应浓度的3-NNMS。再灌注2 h后,心尖取血,取大鼠右下肢股直肌组织进行检测。苏木精-伊红染色观察大鼠股直肌组织病理形态;ELISA检测血清骨骼肌损伤因子肌酸激酶(Creatine Kinase found in the skeletal muscle,CK-MM)、乳酸脱氢酶、髓过氧化物酶水平,并检测股直肌核因子κB、肿瘤坏死因子α、白细胞介素1β、环氧合酶2、丙二醛、活性氧、超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶水平,以及股直肌ATP水平、ATPase活性、线粒体呼吸控制率(RCR)水平。结果与结论:①与对照组相比,缺血再灌注模型大鼠血清CK-MM、乳酸脱氢酶、髓过氧化物酶水平升高,股直肌核因子κB、肿瘤坏死因子α、白细胞介素1β、环氧合酶2、丙二醛及活性氧水平升高,过氧化氢酶、谷胱甘肽过氧化物酶水平下降,ATPase活性、线粒体呼吸控制率水平降低;细胞形态不规则,炎性细胞浸润明显,细胞出现肿胀。②与0μg/mL组相比,25μg/mL组大鼠血清CK-MM、乳酸脱氢酶水平降低,股直肌核因子κB、环氧合酶2水平降低,活性氧减少,超氧化物歧化酶活性升高;细胞形态较规则,炎性细胞浸润较轻,细胞肿胀现象缓解。③与0μg/mL组相比,125μg/mL组大鼠血清CK-MM、乳酸脱氢酶、髓过氧化物酶水平降低,股直肌核因子κB、肿瘤坏死因子α、环氧合酶2量减少,丙二醛、活性氧水平降低,超氧化物歧化酶、谷胱甘肽过氧化物酶活性升高,线粒体呼吸控制率水平升高;细胞排列较整齐,轮廓较清晰完整,炎性细胞浸润较轻。④结果说明:3-NNMS可以减轻肢体缺血再灌注引起的骨骼肌功能损伤,其作用机制可能是通过改善线粒体功能、减少活性氧产生、降低氧化应激和炎症反应,进而减轻组织损伤,修复骨骼肌功能。

Angiogenesis effect of Astragalus polysaccharide combined with endothelial progenitor cells therapy in diabetic male rat following experimental hind limb ischemia

Background Diabetes mellitus （DM） is a common disease accompanied with a high incidence of hind limb ischemia （HLI）.In recent years,numerous studies demonstrated that endothelial progenitor cells （EPCs） are involved in angiogenesis and maintenance of vascular integrity following HLI.On the other side,it has been proved that Astragalus polysaccharide （APS） could promote angiogenesis.In the present study,we aimed to evaluate the effect of APS and EPCs on enhancing angiogenesis after experimental HLI caused by femoral artery ligation in rats with streptozotocin （STZ）-induced diabetes.Methods Rats （n=110） were randomly assigned to the following groups：sham group,ischemia group,APS group,EPCs group and APS＋EPCs group.APS,EPCs or an equal volume of vehicle was administered intramuscularly after HLI induction,and 6 rats were assessed by angiography at 28 days after induction of HLI,6 rats were sacrificed at the same time point to take histological studies,biochemical tests were also performed at that point in the rest rats.Results APS or EPCs treatment induced an increase,respectively,in the protein expression of vascular endothelial growth factor （VEGF） （36.61%,61.59%）,VEGF receptor-1 （VEGFR-1） （35.50%,57.33%）,VEGFR-2 （31.75%,41.89%）,Angiopoietin-1 （Ang-1） （37.57%,64.66%） and Tie-2 （42.55%,76.94%） （P 〈0.05）,after HLI injury.And combined therapy of APS and EPCs enhanced the effort of angiogenesis after HLI induction in diabetic rats,through elevating protein expression of VEGF （99.67%）,VEGFR-1 （105.33%）,VEGFR2 （72.05%）,Ang-1 （114.30%） and Tie-2 （111.87%） （P〈0.05）.Similarly,mRNA expression of VEGF,VEGFR-1,VEGFR2,Ang-1,Tie-2 also show similar trends as well as protein expression （P〈0.05）.Conclusion APS or EPCs could enhance angiogenesis,and the combined treatment leads to better effort,at least,partially via VEGFNEGFR and Ang-1/Tie-2 signaling pathway.

桃红四物汤通过miR-675/NF-κB信号通路减轻肢体缺血再灌注损伤炎症反应机制研究

目的:基于miR-675/NF-κB信号通路研究桃红四物汤对肢体缺血再灌注损伤炎症反应的影响。方法:78只大鼠分为四组,除正常对照组外,其余三组均复制缺血再灌注损伤模型。于再灌注0、2、4、8 h四个时间点取材骨骼肌,HE染色观察骨骼肌形态;TUNEL荧光染色观察骨骼肌细胞凋亡情况;RT-qPCR检测miR-675-5p、NF-κB p65、p50表达;Western blot检测NF-κB p65、p50蛋白表达;ELISA检测血清TNF-α、IL-1β、IL-6水平。结果:与模型组相比,桃红四物汤组、miR-675阻滞剂组血清TNF-α、IL-1β、IL-6水平降低(均P<0.05);桃红四物汤、miR-675阻滞剂干预,可保护骨骼肌细胞,减轻凋亡程度,与模型组相比,可降低NF-κB p65、p50的表达(均P<0.05)。结论:桃红四物汤可通过减轻炎症反应保护骨骼肌细胞,这一过程可能与miR-675/NF-κB信号通路的激活有关。

星状神经节阻滞对下肢止血带缺血再灌注损伤及术后镇痛的影响

目的:探讨星状神经节阻滞对下肢止血带缺血再灌注损伤及术后镇痛的影响。方法:在徐州医科大学附属医院麻醉科2020年2月~2022年6月收治的所有下肢损伤手术患者中选取60例为研究对象,采用随机数字表法分为对照组(n=30)与观察组(n=30)两组,观察组采用星状神经节阻滞法进行神经阻滞,对照组患者不进行神经阻滞。分别对比两组患者上止血带前(T0)、止血带充气10 min(T1)、止血带充气30 min(T2)止血带充气60 min(T3)、止血带充气90 min(T4)、松止血带后10 min(T5)、松止血带后30 min(T6)、松止血带后60 min(T7)心率(HR)情况、丙二醇(MDA)、超氧化物歧化酶(SOD)以及炎性因子肿瘤坏死因子(TNF)-α和白细胞介素8(IL-8)表达水平、术后镇痛情况以及术后并发症(术后出血、术后发热以及肺不张)发生率。结果:两组患者T0、T6、T7时刻HR相比差异无统计学意义(P>0.05),T1~T5时刻,观察组的HR明显低于对照组,差异有统计学意义(P<0.05),;两组患者T0时刻MDA、SOD、TNF-α和IL-8相比差异无统计学意义(P>0.05),T7时刻观察组SOD明显高于对照组,MDA、TNF-α和IL-8均低于对照组,差异均有统计学意义(P<0.05);观察组患者的首次镇痛药物服用时间长于对照组患者,48 h镇痛泵使用次数少于对照组患者,差异有统计学意义(P<0.05);观察组患者并发症发生率(3.33%)低于对照组(26.66%),差异有统计学意义(P<0.05)。结论:在对于下肢止血带缺血再灌注损伤患者的治疗中,运用星状神经节阻滞的方法能有效减轻止血带为患者所带来的疼痛,避免脏器损伤,减轻缺血再灌注损伤出现的可能,提高疾病的预后效果,运用效果显著。

常温机械灌注技术在离断肢体保存中的作用研究进展

肢体离断伤在临床工作中较为常见,对离断肢体实施安全有效的保护是肢体再植成功的关键。常温机械灌注技术已经在器官移植领域取得很大突破,可长时间维持器官和组织的活性功能,延长其保存时间,在大动物模型以及临床应用中得到了很好的验证。同时这项技术有望为离断肢体的保存和功能恢复提供新的参考。因此,本文就静态冷保存在离断肢体保存中存在的问题、机械灌注的发展历程、离断肢体常温机械灌注的临床应用现状以及有待解决问题进行综述,并展望其发展方向和临床应用前景,以期推动该技术在临床广泛应用。

人源化基因修饰猪血红细胞常温机械灌注技术对人断肢的保护作用

目的探讨人源化基因修饰猪血红细胞常温机械灌注对人离断肢体的保存作用。方法采用人源化基因修饰猪血红细胞灌注人离断肢体6 h。每小时取灌注液检测血氧分压、Na^(+)、K^(+)、Ca^(2+)、pH值、葡萄糖、乳酸及肌酸激酶水平,取浅层屈肌检测肿瘤坏死因子(TNF)-α、白细胞介素(IL)-2、IL-1变化。灌注0 h、6 h取适量前臂浅层屈肌,进行病理学检查,观察骨骼肌细胞间隙及糖原消耗情况。每2 h取适量前臂血管,检测血管内皮细胞凋亡情况。灌注开始前及灌注6 h行X线造影,观察指端末梢血管充盈度。结果灌注过程中氧分压处于正常范围。Na^(+)在1 h出现高峰,达到138.7 mmol/L,之后波动于正常范围;K^(+)在2 h出现高峰,为6.08 mmol/L,之后下降,波动于正常范围;Ca^(2+)在4 h达高峰,为1.03 mmol/L。葡萄糖在灌注开始时逐渐降低,灌注2 h时达最低值17.7 mmol/L,之后维持动态平衡。pH值在灌注6 h降低为7.28,乳酸水平在灌注1 h时升高,达到9.6 mmol/L,之后逐渐呈下降趋势。肌酸激酶水平从灌注开始升高,于2 h到达高峰,为20030 U/L,之后下降,在灌注结束时保持稳定。灌注结束肌纤维形态正常,肌纤维间隙略有增大,骨骼肌糖原未见明显蓄积。灌注0 h时血管内皮凋亡细胞数量较多,6 h时凋亡细胞数量减少。灌注0 h时血管充盈明显,6 h时指间部分血管充盈程度减低。结论人源化基因修饰猪血红细胞常温机械灌注人断肢能持续稳定的供能供氧,保持灌注液离子酸碱度平衡,维持细胞正常代谢,对离断肢体有一定保护作用。

基于生物模型网络的肢体缺血再灌注损伤关键基因及免疫浸润机制研究

目的:建立生物模型网络,分析肢体缺血再灌注损伤(IRI)关键基因及免疫浸润机制并实验验证。方法:通过GEO数据库获取IRI芯片。使用随机森林、LASSO回归和SVM算法筛选IRI相关特征基因。构建肢体IRI动物模型,用RT-qPCR实验验证关键基因mRNA相对表达量。用CIBERSORT算法预估IRI与筛选出的潜在生物标志物的生物信息学关联。结果:共获取差异基因169个,其中上调基因116个,下调基因53个。通过2种机器学习算法筛选到最相关的4个相关特征基因(WNT5A、PLCG、ITPR1、CAMK2A),RT-qPCR结果显示,与对照组相比,IRI组中WNT5A、PLCG、ITPR1、CAMK2A表达量上调(P<0.01)。免疫细胞浸润显示,IRI组中浆细胞、滤泡辅助性T细胞、初始世噬细胞、M2型巨噬细胞的浸润程度降低(P<0.05);M1型巨噬细胞、静止树实状细胞、活化肥大细胞的浸润程度增高(P<0.05)。静息状态肥大细胞与单核细胞(r=0.76)、M2型巨噬细胞与CD8+T细胞(r=0.75)、M2型巨噬细胞与活化肥大细胞(r=0.75)等呈现正相关;静息状态肥大细胞与M2型巨噬细胞(r=-0.88)、M2型巨噬细胞与M1型巨噬细胞(r=-0.86)、活化的自然杀伤细胞与初始B细胞(r=-0.75)等之间呈现负相关。WNT5A记忆B细胞、记忆CD4+T细胞呈负相关;PLCG与NK激活细胞呈正相关;CAMK2A与初始B细胞呈正相关;ITPR1与γδT细胞呈正相关。结论:WNT5A、PLCG、ITPR1、CAMK2A可能在肢体IRI发病过程中起重要作用,并与多种免疫细胞存在相关性,在防治肢体IRI的过程中,同时应重视免疫细胞作用。

吸入性七氟烷对创伤性下肢骨折患者缺血再灌注损伤的防治效果研究

目的:探讨在创伤性下肢骨折患者术中应用吸入性七氟烷麻醉对缺血再灌注损伤的防治效果。方法:回顾性分析2020年3月-2022年6月郑州市骨科医院收治的124例创伤性下肢骨折患者临床资料,经抽签法将其分为观察组和对照组,每组各62例。两组患者术中均予以丙泊酚靶控输注麻醉,观察组在此基础上全程予以吸入性七氟烷辅助麻醉,比较两组患者术后基础体征、肾脏组织及心肌组织功能,免疫功能变化情况、缺血再灌注损伤发生情况及苏醒质量。结果:术后,观察组的尿酸(UA)、尿素氮(BUN)、血肌酐(SCr)、肾上腺皮质醇(Cor)等肾脏功能指标水平均低于对照组,差异有统计学意义(t=20.984、29.043、15.350、8.682,P<0.05);术后,观察组的肌红蛋白(Mb)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)水平均低于对照组,差异有统计学意义(t=14.695、5.177、19.790、14.086,P<0.05);术后,观察组T淋巴细胞亚群CD3+、CD4+、CD8+水平均高于对照组,差异有统计学意义(t=12.035、7.605、7.123,P<0.05);术后,观察组的肾脏损伤、心肌损伤发生率均低于对照组,差异有统计学意义(χ^(2)=6.306、5.994,P<0.05);苏醒后,观察组Ricker镇静评分(SAS)、心率(HR)、平均动脉压(MAP)、血氧饱和度(SaO2)与对照组比较,差异无统计学意义(t=0.922、0.756、1.895、1.808,P>0.05)。结论:在创伤性下肢骨折患者术中应用吸入性七氟烷辅助麻醉可有效降低缺血再灌注后肾脏、心肌损伤发生,对提升患者免疫功能具有积极意义,同时此麻醉方案为影响患者术后苏醒质量,苏醒后基础体征指标也较为稳定。

β-七叶皂甙钠对肢体缺血再灌注损伤的保护作用

目的 :观察 β 七叶皂甙钠对肢体缺血再灌注损伤的保护作用。方法 :用兔造成肢体缺血再灌注损伤动物模型。实验分对照组、缺血再灌注组和 β 七叶皂甙钠组。取血浆测定丙二醛、肌酸磷酸激酶、谷草转氨酶和乳酸脱氢酶含量。取骨骼肌标本测定丙二醛、髓过氧化酶活性、肌细胞线粒体钙含量和组织湿 /干重比值。结果 :缺血再灌注组与对照组比较 ,血浆和骨骼肌的各项生化指标显著增高 (P <0 .0 1) ;使用 β 七叶皂甙钠后 ,血浆及骨骼肌各项测定指标较缺血再灌注组相比明显降低 (P <0 .0 5 ,P <0 .0 1)。结论 :β 七叶皂甙钠可减轻肢体缺血再灌注损伤 。

缺血预处理对大鼠肢体缺血再灌注损伤保护效应的实验研究

目的探讨缺血预处理不同时间方案对肢体缺血再灌注损伤保护作用的差异性,选择合理的缺血预处理时间。方法 40只SPF级SD大鼠随机分成5组:假手术组(A组,仅行开腹,分离腹主动脉不阻断);缺血再灌注组(B组,夹闭腹主动脉缺血2 h后再灌注2 h);C、D、E组:分别阻断腹主动脉1、5和10 min,再灌注1、5和10 min,重复3个循环后进行2 h缺血2 h再灌注。测定血清超氧化物歧化酶(SOD)、丙二醛(MDA)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)水平,观察各组氧化/抗氧化指标及炎症因子表达的差异性。结果 D组SOD活性升高、MDA含量下降,与B组比较差异有统计学意义(P<0.05);E组改变更明显,和D组比较差异有统计学意义(P<0.05)。与B组比较,C、D、E组的IL-6、TNF-α明显升高,差异均有统计学意义(P<0.05);E组的各炎症因子水平最高,与C组比较差异均有统计学意义(P<0.05)。结论预缺血时间与氧化损伤的保护作用在一定时间窗内呈平行关系,预缺血并无明显抗炎作用,过长时间预缺血甚至能导致全身性炎症反应;5 min/3个循环缺血预处理方案较为适宜。

一氧化氮、内皮素-1对大鼠肢体缺血/再灌注后脑损伤的影响

目的 :研究一氧化氮 (NO)和内皮素 1(ET 1)在大鼠肢体缺血 /再灌注 (LI/R)后脑损伤中的作用 ,探讨NO/ET 1平衡关系的变化对脑损伤的影响。方法 :在大鼠LI/R损伤模型上 ,应用NO合成前体物质L 精氨酸 (L Arg)、一氧化氮合酶 (NOS)抑制剂氨基胍 (AG)、ETA 受体阻断剂BQl2 3进行干预 ,观察血浆NO、ET 1、MDA、XOD、SOD、LDH及脑组织tNOS、iNOS、cNOS、NO、ET 1、MDA、XOD、MPO、SOD的变化。结果 :与对照组比较 ,I/R组血浆MDA、XOD、LDH及脑组织MDA、XOD、MPO升高 ,SOD活性降低 (P <0 .0 1) ,脑组织tNOS和iNOS明显升高 ,而cNOS明显降低 (P <0 .0 1) ,I/R组血浆及脑组织NO、ET 1增加 ,NO/ET 1比值降低 ,脑损伤加重。应用L Arg及BQ12 3后 ,血浆及脑组织NO/ET 1比值较I/R组升高 ,脑损伤减轻 ,应用AG后 ,NO/ET 1比值降低 ,脑损伤进一步加重。结论 :肢体缺血 /再灌注后 ,一氧化氮与内皮素 l的比值降低时脑损伤加重。

局部低温对肢体缺血/再灌注损伤的保护作用实验研究

目的：探讨局部低温对肢体缺血／ 再灌注损伤的保护作用。方法：４８ 只兔分成常温、甘露醇、１５ ℃、１０ ℃和５ ℃共５ 组。血管夹阻闭股动脉。５ｈ 后放松，并施以保护因素。胫前肌镜检。静脉血生化检测。结果：各项检查均提示低温组有意义，１５ ℃组及１０ ℃组更好。结论：局部低温可减轻肢体缺血／ 再灌注损伤。

无创性肢体缺血预适应增强糖尿病大鼠缺血/再灌注损伤后心肌抗氧化能力

目的研究无创性肢体缺血预适应对糖尿病大鼠心肌缺血/再灌注损伤的保护作用,并从氧化-抗氧化角度初步探讨其作用机制。方法大鼠经尾静脉一次性注射链脲佐菌素(STZ)造成急性糖尿病模型后,被随机分为缺血/再灌注(I/R)、心脏缺血预适应(CIP)和无创肢体缺血预适应(NLIP)3组。NLIP组连续3d经历左后肢缺血预适应。d4,各组动物均经历心肌缺血/再灌注损伤,CIP组于缺血前行心肌缺血预适应。连续监测血压和心电图变化,检测心肌梗死范围,测定心肌组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、黄嘌呤氧化酶(XOD)活性以及丙二醛(MDA)含量。结果成模动物表现出血糖明显升高,体重下降。与I/R组比较,NLIP及CIP组ST-段抬高幅度降低,室早和室速出现时间推迟,持续时间缩短,室性心律失常发生率降低,心肌梗死范围缩小,SOD、GSH-PX活性升高,XOD活性降低,MDA含量减少。结论NLIP对糖尿病大鼠具有与CIP程度相当的心脏保护作用,其机制与增强心肌抗氧化能力有关。

远程预处理对兔脊髓缺血再灌注损伤的保护作用(英文)

目的:探讨远程预处理对兔脊髓缺血再灌注损伤的保护作用。方法:20只成年雄性新西兰大白兔随机分成2组(各组n=10),即对照组和远程预处理(RPC)组。所有动物脊髓缺血前1h戊巴比妥钠麻醉动物(30mg/kg,iv)。RPC组动物麻醉后进行双后肢短暂缺血2次(充气式压力止血带环扎双后肢,压力26.6kPa,阻断10min,松开10min,再阻断10min),最后一次缺血后再灌注30min,阻闭肾下腹主动脉20min,制作兔脊髓缺血模型。对照组动物不进行双后肢短暂缺血,其余同RPC组。再灌注后4,8,12,24和48h分别对动物后肢运动功能评分。再灌注48h后,处死动物取脊髓(L5～7),石蜡包埋切片行组织病理学观察。结果:RPC组神经功能评分在各时间点均明显高于对照组(P=0.000);与对照组相比,RPC组脊髓前角正常神经细胞数明显增多(P=0.000),且神经功能评分与脊髓前角正常神经细胞计数之间有显著相关性(r=0.868,P<0.01)。结论:远程预处理对兔脊髓缺血再灌注损伤有显著的保护作用。

非创伤性肢体缺血预适应对心肌缺血再灌注损伤的影响

目的探讨非创伤性肢体缺血预适应对缺血再灌注心肌是否具有早期保护作用。方法Wistar大鼠36只,随机分为假手术对照组(C组);缺血再灌注组(I组);经典缺血预适应组(PC组);非创伤性肢体缺血预适应组(PL组)。建立体内大鼠心肌缺血再灌注的动物模型,分别结扎前降支30min,再灌注120min,观察大鼠血流动力学参数、血中磷酸肌酸激酶(CPK)及乳酸脱氢酶(LDH)含量及心肌梗死面积的变化。结果平均动脉压(MAP)、心率(HR)组间比较无显著性差异。I组CK及LDH含量明显升高(P<0.05);PC组、PL组与I组比较,心肌梗死范围明显缩小(P<0.05)。结论非创伤性肢体缺血预适应对心脏缺血再灌注损伤具有早期保护作用,能明显缩小心肌梗死面积。