Changes of proton transportation across the innner mitochondrial membrane and H＋^-ATPase in endotoxic shock rats

To investigate the changes of protontransportation across the inner mitochondriai membrane(IMM) and H^ -ATPase of hepatocytes in endotoxic shockrats.     

Levosimendan in rats decreases acute kidney injury after cardiopulmonary resuscitation by improving mitochondrial dysfunction

BackgroundAcute kidney injury (AKI), the most common complication after cardiac resuscitation, is highly prevalent and harmful. There is increasing evidence that levosimendan can improve cardiac output, increase renal blood flow, and prevent AKI. As a novel calcium sensitizer, levosimendan may exert its protective effect via mitochondria.MethodsRat models of asphyxia-induced cardiac arrest and cardiopulmonary resuscitation (CPR) were set up. Thirty healthy adult male SD rats were randomly divided into CPR group (CPR group, n=10), levosimendan-treated group (levo group, n=10), and sham-operated group (sham group, n=10). Twelve hours after CPR, serum renal function indicators were measured, the kidney injury and mitochondrial morphological changes were observed. Oxygen uptake of the mitochondria, mitochondrial adenosine triphosphate (ATP) and mitochondrial free Ca²⁺ concentration were measured. Oxidative stress-related indicator levels in rat kidney tissues were further detected to analyze the differences in apoptosis rates among these three groups. Mitochondrial optic atrophy 1 (Opa1), dynamin-related protein 1 (Drp1), and apoptosis-related proteins were detected using Western blotting.ResultsCompared with the sham group, the CPR group had a significant increase in renal tissue damage. PAS staining and HE stains confirmed that CPR led to renal histopathological damage and destruction of the mitochondrial structure. Levosimendan improved the histopathological and ultrastructural damages of kidneys. Further analysis revealed that mitochondrial ATP content, NADH dehydrogenase, succinate dehydrogenase/cytochrome C oxidase, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (CSH-Px) decreased. Free Ca²⁺ concentration and malondialdehyde (MDA) significantly increased (all P<0.05) in the kidney tissues of rats in the CPR group. However, mitochondrial ATP content, NADH dehydrogenase, succinate dehydrogenase/cytochrome C oxidase, SOD, CAT, and CSH-Px increased, whereas free Ca²⁺ concentration and MDA decreased (all P<0.05) in the levo group. The apoptosis rate increased in the CPR group. There were significantly increased levels of Drp1 protein levels, and significantly decreased Opa1 expression (all P<0.05). However, the levo group showed the opposite effects (all P<0.05).ConclusionsLevosimendan can alleviate AKI following CPR, which may be achieved by improving mitochondrial dysfunction and suppressing the mitochondrial apoptosis pathway.     

Inhibition of mitochondrial respiratory function by an organic solvent extractable component from an extract of burn eschar.

Saline extracts of burn eschar (CEBE) and normal skin (CENS) caused inhibition to mitochondrial respiration and inner membrane function. Ethyl acetate extracts from CEBE (D1) and CENS (D'1) caused depression of the Respiratory Control Ratio, (RCR), an inhibition of respiration rate in state 3 and stimulation to state 4 respiration. Excellent linear correlations exist between the degree of inhibition to state 3, rate of stimulation to state 4 respiration and the logarithm of doses of D1 and D'1. The effective dose ranges (0.75-0.25 mg/ml for D1 and 4-1 mg/ml for D'1) differ by one order of magnitude. The activity of NADH dehydrogenase and succinate dehydrogenase of mitochondria after incubation with the highest toxic dose of D1 or D'1 remained normal. Dinitrophenol (DNP)-stimulated respiration was moderately inhibited by D1 and D'1. No change of oligomycin-sensitive ATPase activity was demonstrated. Exogenous malondialdehyde (MDA) did not show any inhibitory effect. Preliminary studies show that D1 contains a family of free fatty acids (FFA). Incubation of normal mitochondria with D1 increased the content of saturated FFA and a decrease of unsaturated FFA. The role of other peroxidative products is under investigation.     

Effects of seawater immersion on the functions of mitochondria of myocardium and hepatocyte in hemorrhagic shock rats

wereheldabovewater,thevalueofBPwasrecorded for1hourandthehemodynamicindexeswere measured.Incontrolgroup,theratswereneither exsanguinatednorimmersedinseawaterandallother treatmentsweresimilar.Preparationofmitochondriaandsub mitochondriaTheleftventricularmuscleandliver tissuewereobtainedfromtheseratskilledimmediately afterthehemodynamicindexesweremeasured.The mitochondriaandsub mitochondriafromventricular muscleandlivertissue(6g/eachsample)were extractedthroughdifferentialcentrifugation,then su…     

Glucose homeostasis in a guinea pig model of hemorrhagic shock

This study aimed to define the interrelationships of hepatic mitochondrial energy-linked dysfunction, glucose homeostasis, and hepatic adenine nucleotide content in a guinea pig model of hemorrhagic shock. Hepatic mitochondria from shocked animals demonstrated significant decreases in state 3 respiratory rate with each of several substrates. Uncoupled oxidative phosphorylation was detected in mitochondrial preparations from 14 of the 21 hemorrhaged animals. Substrates linked to the cytochrome chain via NADH/NAD⁺ were more sensitive in detecting mitochondrial function than succinate. Hepatic glycogen depletion was a prominent feature following shock but the sequence of glycogen exhaustion and hypoglycemia occurred independently of the status of oxidative phosphorylation. There was no significant difference in the correlation coefficient between the log of the hepatic glycogen content and the blood glucose correlation in those animals with coupled (0.84) and uncoupled oxidative phosphorylation (0.87). ATP decreased significantly in shocked animals (0.41 ± 0.03 μmole/g) compared with controls (1.37 ± 0.10, P < 0.01) but there was no difference between animals with coupled versus uncoupled oxidative phosphorylation. However, the shock animals that remained normal or hypoglycemic had significantly greater hepatic ATP (0.46 ± 0.04 μmole/g) than shock animals that became hypoglycemic (0.31 ± 0.05, P < 0.05). This study indicated that important differences exist between the guinea pig and the rat with regard to effects of shock on glucose homeostasis. These differences may reflect known species differences in the intracellular mechanisms that regulate gluconeogenesis. If so, the guinea pig may be more appropriate than the rat as a model of human shock.     

L-精氨酸对内毒素诱导大鼠肺组织线粒体损伤的影响

目的 评价L精氨酸(L-Arg)对内毒素(LPS)诱导大鼠肺组织线粒体损伤的影响,探讨其减轻内毒素性急性肺损伤的作用机制.方法 雄性SD大鼠24只,随机分为3组(n=8):假手术组(S组)、LPS组和L-Arg组.LPS组和L-Arg组静脉注射LPS 5 mg/kg(用生理盐水稀释至1 ml/kg),S组给予生理盐水1 ml/kg,3 h后L-Arg组腹腔注射L-Arg 500 mg/kg(用生理盐水稀释至1 ml/kg),S组和Au组给予生理盐水1 ml/kg.注射L-Arg或生理盐水后3 h.取肺组织.提取线粒体,测定超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、ATPase、丙二醛(MDA)、一氧化氮合酶(NOS)、诱生型一氧化氮合酶(iNOS)、结构型一氧化氮合酶(cNOS)、一氧化氮(NO)的水平、线粒体膜肿胀度、线粒体活力和线粒体膜流动性;电镜观察肺组织超微结构.结果 与S组比较,LPS组SOD、GSH-Px、ATPase、线粒体活力和线粒体膜流动性降低,MDA、NOS、iNOS、NO及线粒体膜肿胀度升高(P<0.01);与LPs组比较,L-Arg组SOD、GSH.Px、ATPase、线粒体活力和线粒体膜流动性升高,MDA含量和线粒体膜肿胀度降低(P<0.05).L-Ars组细胞肿胀、线粒体肿胀和空泡化的程度轻于LPS组.结论 L-Arg可减轻LPS诱导大鼠肺组织线粒体损伤,其机制与增强抗过氧化能力有关.     

缺血后处理对大鼠肝缺血再灌注时肝细胞线粒体损伤的影响

目的 评价缺血后处理对大鼠肝缺血再灌注时线粒体损伤的影响.方法 雄性SD大鼠30只,体重180～230 g,随机分为3组(n=10):假手术组(S组)、肝缺血再灌注组(IR组)和缺血后处理组(Ipo组).IR组和Ipo组采用阻断肝门60 min再灌注6 h的方法 制备肝缺血再灌注模型,Ipo组缺血60 min时再灌注10 s、缺血10 s,反复6次,进行缺血后处理.于再灌注6 h时取静脉血样,测定血清谷丙转氨酶(ALT)及天门冬氨酸氨基转移酶(AST)活性,然后取肝组织,制备病理切片及分离肝细胞,电镜下观察线粒体超微结构,测定线粒体膜电位及线粒体Na+-K+-ATP酶活性.结果 与S组比较,IR组和Ipo组血清ALT和AST活性升高,线粒体Na+-K+-ATP酶活性及线粒体膜电位降低(P<0.01);与IR组比较,Ipo组血清ALT和AST活性降低,线粒体Na+-K+-ATP酶活性及线粒体膜电位升高(P<0.05或0.01).Ipo组线粒体损伤程度轻于IR组.结论 缺血后处理可减轻大鼠肝缺血再灌注时肝细胞线粒体损伤.     

瑞芬太尼对过氧化氢处理脐静脉内皮细胞的抗氧化应激作用

目的以人脐静脉内皮细胞为细胞模型,建立过氧化氢处理的氧化应激模型,研究瑞芬太尼的抗氧化应激保护机制,并确定信号转导通路。方法过氧化氢0.1mol/L孵育原代培养的人脐静脉内皮细胞,建立细胞损伤模型,然后进行瑞芬太尼保护及相关通路研究。实验共分为九组:空白对照组(C组)、过氧化氢组(H1组)、过氧化氢+SP600125组(H2组)、过氧化氢+SB203580组(H3组)、过氧化氢+PD98059组(H4组);过氧化氢+瑞芬太尼组(HR1组)、过氧化氢+瑞芬太尼+SP600125组(HR2组)、过氧化氢+瑞芬太尼+SB203580组(HR3组)、过氧化氢+瑞芬太尼+PD98059组(HR4组)。H1组、H2组、H3组和H4组仅进行MAPK通路阻断实验,HR1组、HR2组、HR3组和HR4组分别加入瑞芬太尼10ng/ml保护1h。随后分别检测超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量及Caspase-3活性,观察瑞芬太尼抗氧化应激作用并初步确定转导通路;利用RT-PCR观察瑞芬太尼10ng/ml处理前后c-Jun的表达水平,确定转导通路的信号分子。结果H1、H2、H3、H4组SOD活性明显低于C组,MDA含量明显高于C组(P0.05);HR1组SOD活性明显高于H1组,MDA含量明显低于H1组(P0.05);HR2组与H2组SOD活性及MDA含量差异无统计学意义;HR3组SOD活性明显高于H3组,MDA含量明显低于H3组(P0.05);HR4组SOD活性明显高于H4组,MDA含量明显低于H4组(P0.05)。H1、H2、H3、H4组Caspase-3活性明显高于C组(P0.05)。H1组和HR1组c-Jun mRNA表达量明显高于C组,且HR1组明显低于H1组(P0.05)。结论瑞芬太尼10ng/ml可激活JNK通路及其下游信号分子c-Jun,上调SOD活性,降低MDA含量,进而起到抗氧化应激作用。     

Protection of melatonin against damage of sperm mito-chondrial function induced by reactive oxygen species

Aim: To study the mitochondrial function damage of sperm in-duced by reactive oxygen species (ROS) and the protection of melatonin (MLT) against the damage. Methods: Normal function spermatozoa were selected from semen samples by Percoll gradi-ent centrifugation technique. The ROS generated by the hypoxan-thine xanthine oxidase system was incubated with the normal sper-matozoa in the presence or absence of MLT (6 retool/L) for 30 and 60 minutes.     

Hepatic microsomal adenosine triphosphatase and mitochondrial function. Response to cold and warm ischemia

We investigated the response of mitochondrial function and microsomal adenosine triphosphatase (ATPase) activity in rat liver tissue subjected to in vitro ischemia at either 0 degree C to 4 degrees C or 37 degrees C for 30 to 60 minutes. Mitochondrial coupling, expressed as respiratory control index, was preserved at up to 60 minutes' cold ischemia. However, respiratory control index was decreased significantly from control by 30 minutes of warm ischemia. Both microsomal magnesium-activated ATPase and sodium-potassium ATPase activity were significantly increased by 60 minutes of warm ischemia yet were unaltered by 60 minutes of ischemia at 0 degree C to 4 degrees C. Warm ischemia produces deleterious effects on energy-generating (mitochondria) and energy-utilizing (ATPase) activity. Hypothermia provides a significant prolongation of cellular viability in ischemic tissue in terms of bioenergetic status. In addition to organ procurement and transplantation, hypothermic cytoprotection may prove valuable in areas such as shock, ischemia, and other clinical conditions of compromised visceral perfusion.     

大鼠脊髓损伤后线粒体代谢功能和还原型谷胱甘肽水平的变化

目的 探讨大鼠脊髓损伤后伤段脊髓线粒体代谢功能和还原型谷胱甘肽(GSH)水平的变化.方法 取48只SD大鼠,随机分为假手术组(对照组)和脊髓损伤组(SCI组),每组又分为处理后6、12、24 h 3个时相组,每个时相组8只,分别提取伤段脊髓的线粒体,测定线粒体呼吸功能[呼吸Ⅲ态(R3)、呼吸Ⅳ态(R4)、呼吸控制率(RCR)及磷氧比(P/O)值]、三磷酸腺苷酶(ATPase)活性(Na+、K+-ATP酶和Ca2+、Mg2+-ATP酶活性)及GSH的变化.结果 SCI组在伤后6、12、24 h伤段脊髓线粒体的R3、RCR及P/O均显著低于对照组,R4显著高于对照组,差异有统计学意义(P＜0.05).SCl组Na+、K+-ATP酶和Ca2+、Mg2+-ATP酶较对照组明显降低,伤后6 h急剧下降,12 h后稍有代偿性升高,24 h后又下降,与对照组比较差异有统计学意义(P＜0.05).GSH水平SCI组与对照组相比明显降低,以伤后12 h最为明显,差异有统计学意义(P＜0.05).结论 脊髓损伤后伤段脊髓线粒体的呼吸功能、ATPase酶活性及GSH水平明显下降,说明脊髓损伤后线粒体能量代谢功能和自由基清除能力均受到明显损害.     

Altered ryanodine receptor of canine cardiac sarcoplasmic reticulum and its underlying mechanism in endotoxin shock.

Effects of endotoxin administration on ryanodine receptor in canine cardiac junctional sarcoplasmic reticulum (SR) were studied. The results show that the Bmax for [3H]ryanodine binding to cardiac junctional SR was decreased by 25% (8 +/- 0.38 vs 6 +/- 0.41 pmole/mg protein for control and endotoxic, respectively; (P less than 0.01) while the kd (13.7 +/- 1 nM for control vs 13.2 +/- 2 nM for endotoxic) was unaffected 4 hr following endotoxin administration. Ca2+ activated [3H]ryanodine binding in both groups sigmoidally but the Vmax for Ca2+ activation was decreased by 24% (P less than 0.05) while the S0.5 and the Hill coefficient values remained unchanged after endotoxin injection. Caffeine, ATP, and AMP-PCP activated while calmodulin, SKF-525A, ruthenium red, and Mg2+ inhibited [3H]ryanodine binding in both groups but the A0.5 (concentration requires for half-maximum activation) and the I50 (concentration requires for half-maximum inhibition) for the above-mentioned activators and inhibitors, respectively, were unaffected during endotoxin shock. Digestion of cardiac SR isolated from control dogs with phospholipase A2 inhibited [3H]ryanodine binding and the inhibition was reversed completely by the addition of phosphatidylserine. Addition of phosphatidylserine to cardiac SR isolated from endotoxic dogs stimulated [3H]ryanodine binding and the stimulation represents a complete reversal of the inhibition caused by endotoxin administration. Based on these findings together with previous observation that phospholipase A2 activity is activated during endotoxin shock, it is concluded that endotoxin administration decreases the number of ryanodine receptor in canine cardiac junctional SR and the decrease in ryanodine receptor is associated with a mechanism involving a modification of membrane lipid microenvironment in response to phospholipase A2 activation.     

Bacteremic shock: aspects of high-energy metabolism of rat liver following living Escherichia coli injection

Sublethal and lethal doses of living Escherichia coli (E. coli) (serotype: O-18) were injected intravenously into rats. The amounts of live E. coli injected were 0.5 ml of 0.8 – 1.0 × 10⁹ or 2.5 – 3.0 × 10⁹ organisms/ml saline per 100 g body weight for the sublethal (SL) or lethal (L) groups, respectively. The adenylate energy charge (ATP + 1/2ADP/ATP + ADP + AMP) and free NAD⁺/NADH ratios of the mitochondrial and cytoplasmic compartments in rat livers were measured at 3, 6, 12, and 24 hr following E. coli injection. At 6 hr in both groups, the hepatic energy charge levels were decreased from 0.856 in controls to 0.823 (SL) and 0.812 (L), associated with elevated mitochondrial NAD⁺/NADH ratios (P < 0.05). At 12 hr the sublethal group maintained the above state. In the lethal group, however, the hepatic energy charge was markedly decreased (P < 0.001), associated with remarkably decreased NAD⁺/NADH ratios in both mitochondria and cytoplasm (P < 0.01 and P < 0.001). In both groups the total ketone body (acetoacetate + β-hydroxybutyrate) contents were decreased with an elevation of mitochondrial NAD⁺/NADH. From these results, it is concluded that the difference between the sublethal and lethal groups is characterized by the progressive deterioration of the high-energy level in the lethal group, possibly due to restricted mitochondrial respiration. In addition, it is suggested that the elevated mitochondrial NAD⁺/NADH ratio may play a role in decreased ketone body contents in the liver following E. coli injection.     

褪黑素在活性氧致精子线粒体功能损伤中的保护作用

目的 :探讨活性氧 (ROS)对精子线粒体功能的损伤以及褪黑素 (MLT)的保护作用。　方法 :采用Percoll梯度离心法选择具有正常生理功能的精子 ,作为本实验的正常精子模型。应用次黄嘌呤—黄嘌呤氧化酶体系产生ROS ,在MLT存在与不存在情况下 ,与精子模型分别孵育 30和 6 0min后 ,采用酶组织化学方法分析精子线粒体部位的琥珀酸脱氢酶 (SDH)活性 ,采用Rhodamine 1 2 3(Rh1 2 3)荧光探针标记精子 ,通过流式细胞仪检测线粒体膜电位。　结果 :正常精子与ROS孵育后 ,精子线粒体膜电位明显降低 ,线粒体SDH活力降低极为显著 ;而MLT则减轻了ROS对精子线粒体功能的损伤。　结论 :ROS可通过对精子线粒体膜电位和SDH活力的影响 ,而导致精子线粒体功能损伤 ;MLT可通过其有效的抗氧化能力 ,保护精子对抗ROS对其线粒体功能的损伤     

牛磺酸对烫伤大鼠心肌线粒体成分和酶活性的保护作用

目的 了解牛磺酸对大鼠烫伤后心肌线粒体成分和酶活性变化的影响.方法 将120只大鼠背部脱毛后造成30%TBSA的Ⅲ度烫伤.分为烫伤组(60只),伤后腹腔注射等渗盐水(4mL·kg-1·1%TBSA-1);牛磺酸治疗组(60只),伤后腹腔注射20 g/L牛磺酸液(200 mg/kg).伤后1、3、6、12、24、48 h处死大鼠.取心肌组织检测心肌线粒体琥珀酸脱氢酶(SDH)、细胞色素c氧化酶(CCO)、超氧化物歧化酶(SOD)、Ca2+-腺苷三磷酸酶(ATPase)活性和细胞色素c、细胞色素aa3、丙二醛(MDA)、细胞质及线粒体内ca2+含量.另取10只大鼠作为对照组,模拟烫伤不予补液,1 h后处死大鼠取心肌组织检测以上指标.结果 烫伤组大鼠伤后1 h CCO活性即开始下降,伤后6、12 h下降最明显,而SDH活性在伤后6 h下降最明显,且各时相点均低于对照组;牛磺酸治疗组CCO和SDH下降不明显,伤后3、6、12 h CCO活性与烫伤组比较,差异有统计学意义(P＜0.05).伤后3、6、12、及24 h烫伤组心肌线粒体细胞色素c和细胞色素aa3均显著降低.而牛磺酸组虽然有所下降,但以上4个时相点的值均高于烫伤组(P＜0.05).烫伤组SOD活性在伤后3、6、12 h均显著性下降,ca2+ATPase活性在伤后3、6、12及24 h均有不同程度下降;而牛磺酸治疗组虽然有所下降,但以上4个时相点SOD、Ca2+-ATPase值均高于烫伤组(P＜0.05).伤后3～48 h烫伤组、牛磺酸治疗组MDA值均高于对照组(P＜0.05),但牛磺酸治疗组低于烫伤组(P＜0.05).伤后1 h烫伤组大鼠心肌线粒体中Ca2+即开始升高为13.7±1.5,伤后3、6、12、24 h分别为24.8±2.6、29.7±3.1、16.3±1.9及13.5±1.7.均高于对照组(10.7±1.6,P＜0.05);心肌细胞质中ca2+在伤后3、6、12、24 h也明显高于对照组(P＜0.05).伤后3、6、12及24 h牛磺酸治疗组大鼠心肌线粒体中ca2+浓度分别为16.8±2.8、18.7±1.9、10.5±1.8及13.3±1.7,均低于烫伤组.结论 牛磺酸对烫伤大鼠心肌线粒体成分和酶活性破坏具有保护作用,其机制与提高线粒体清除氧自由基的能力和减轻Ca2+超载有关.     

氨基胍对内毒素休克大鼠肝损伤的保护作用研究

目的 探讨诱导型一氧化氮合酶(iNOS)抑制剂氨基胍对内毒素休克大鼠肝脏的组织学和超微结构的影响。方法 取雄性wistar大鼠24只．随机分为正常对照组、内毒素对照组和氨基胍治疗组．每组各8只。用大肠杆菌内毒素(LPS)复制大鼠内毒素性休克模型．氨基胍治疗组采用氨基胍治疗。观察并比较三组大鼠肝脏的组织学、超微结构及其血浆一氧化氮(NO)含量的变化。结果 光镜下可见．内毒素组肝组织有散在小脓肿灶形成．肝细胞坏死，中性白细胞浸润．而氨基胍治疗组的肝组织受损程度较轻。电镜下可见，内毒素组的肝细胞核出现融解性空斑．线粒体肿胀和线粒体嵴数量减少．而氨基胍则对肝脏的结构起到一定的保护作用。内毒素对照组血浆NO水平明显高于正常对照组．给予氨基胍治疗后血浆NO水平明显下降．但仍高于正常对照组。结论 氨基胍通过选择性抑制iNOS活性．抑制了大鼠内毒素休克时过量的NO的产生．保护了肝脏的功能．具有潜在的临床应用价值．值得更深入地研究。     

星状神经节阻滞对急性脑梗塞患者红细胞免疫功能的影响

目的探讨星状神经节阻滞（SGB）对急性脑梗塞患者红细胞免疫功能的影响。方法急性脑梗塞患者（病程〈3d）24例，年龄51—64岁，体重52—71kg，随机分为常规治疗组（A组）和常规治疗＋SGB组（B组），每组12例。2组均进行常规治疗。B组以1％利多卡因10ml行SGB，1次/d，双侧交替、10次为一疗程。分别于治疗前1d（T1）、治疗后第1天（T2）、治疗后第5天（T3）、治疗后第10天（T4）清晨空腹取静脉血。采用硫代巴比妥酸法及黄嘌呤氧化酶法测定血浆丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性，酵母菌红细胞免疫花环法测定红细胞C3b受体花环率（RBC-C3bRR）及红细胞免疫复合物花环率（RBC-ICR），孔雀绿比色分析法测定红细胞膜Na^＋ - K^＋ - ATP酶活性。结果与T1相比，A组T3,4时、B组T2-4时血浆MDA含量降低，SOD活性升高，红细胞膜Na^＋ - K^＋ - ATP酶活性升高，A组和B组T3,4时RBC-ICR降低，RBC-C3bRR增高（P〈0．05或0．01）；与A组相比，B组T3,4时血浆MDA含量及RBC-ICR降低，血浆SOD、红细胞膜Na^＋ - K^＋ - ATP酶活性及RBC-C3bRR均升高（P〈0．05或0．01）。结论SGB可降低机体氧化应激反应，提高红细胞膜Na^＋ - K^＋ - ATP酶活性，增强急性脑梗塞患者红细胞的免疫功能。     

The effect of aminoguanidine on blood and tissue lipid peroxidation in jaundiced rats with endotoxemia induced with LPS.

Obstructive jaundice (OJ) is a severe condition that leads to several complications. One of the important problems in OJ is the increased incidence of endotoxemia, which is the result of bacterial translocation (BT) and defective host immune response. Lipid peroxidation (LP) is an important problem in OJ and sepsis in which nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity are increased and antioxidative activity is decreased. Formation of peroxynitrite (ONOO(-)) anion leads to cellular damage and apoptosis. In this experimental study, we explore the effect of specific iNOS inhibitor aminoguanidine (AG) on blood and tissue (liver and renal) LP and iNOS levels in jaundiced rats with endotoxemia induced with lipopolysaccharide (LPS). Rats were randomized into six groups; group A, sham; group B, obstructive jaundice (OJ); group C, OJ + LPS; group D, OJ + AG; group E, OJ + LPS + AG; group F, OJ + AG + LPS. Serum malondialdehyde (MDA) and serum myeloperoxidase (MPO) activity and liver and renal tissue MDA, MPO, and Na(+)/K(+)-ATPase activity levels were detected in biochemical methods. Liver and renal tissue iNOS levels were examined immunohistopathologically. Serum and tissue MDA and MPO levels and tissue iNOS expression were increased significantly in groups B, C, and E, while tissue ATPase levels were decreased significantly in the same groups. In the group treated with AG (group D), serum and tissue MDA and MPO levels and tissue iNOS expression were decreased while tissue ATPase levels were increased significantly. In group F, if AG was administrated before LPS, we observed that serum and tissue MDA and MPO levels and tissue iNOS expression were decreased while tissue ATPase levels were increased significantly. Thus, our study showed that AG had a protective effect when it was administrated before LPS, but it failed to prevent tissue iNOS expression and LP if there was established endotoxemia in OJ.     

Biological significance of enhanced mitochondrial ketogenesis during the early stages after 70% hepatectomy in rats

Ketogenic capacity of mitochondria from the remnant liver of 70% hepatectomized rats was studied in relation to mitochondrial phosphorylative activity. Ketogenic capacity increased to a maximum of 6.04 +/- 0.39 from 3.84 +/- 0.13 of control, with an enhancement of mitochondrial phosphorylative activity 6 hr after hepatectomy, and then decreased to normal levels within 24 hr. Adenylate energy charge, (ATP + 1/2ADP)/(ATP + ADP + AMP), of the remnant liver decreased to 0.825 +/- 0.006 as compared to 0.849 +/- 0.002 of control 6 hr after operation. At 12 hr, total ketone body concentrations of the arterial blood increased concomitant with a fall in ketone body ratio (acetoacetate/3-hydroxybutyrate) which reflects the decreased liver mitochondrial redox (NAD+/NADH) state. These findings suggest that an enhancement of mitochondrial fatty acid oxidation and ketogenesis occurs concomitant with an enhancement of mitochondrial phosphorylative activity in the remnant liver in response to a decreased energy charge after 70% hepatectomy.     

The Effect of Aminoguanidine on Blood and Tissue Lipid Peroxidation in Jaundiced Rats With Endotoxemia Induced With LPS

Obstructive jaundice (OJ) is a severe condition that leads to several complications. One of the important problems in OJ is the increased incidence of endotoxemia, which is the result of bacterial translocation (BT) and defective host immune response. Lipid peroxidation (LP) is an important problem in OJ and sepsis in which nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity are increased and antioxidative activity is decreased. Formation of peroxynitrite (ONOO^?) anion leads to cellular damage and apoptosis. In this experimental study, we explore the effect of specific iNOS inhibitor aminoguanidine (AG) on blood and tissue (liver and renal) LP and iNOS levels in jaundiced rats with endotoxemia induced with lipopolysaccharide (LPS). Rats were randomized into six groups; group A, sham; group B, obstructive jaundice (OJ); group C, OJ + LPS; group D, OJ + AG; group E, OJ + LPS + AG; group F, OJ + AG + LPS. Serum malondialdehyde (MDA) and serum myeloperoxidase (MPO) activity and liver and renal tissue MDA, MPO, and Na⁺/K⁺-ATPase activity levels were detected in biochemical methods. Liver and renal tissue iNOS levels were examined immunohistopathologically. Serum and tissue MDA and MPO levels and tissue iNOS expression were increased significantly in groups B, C, and E, while tissue ATPase levels were decreased significantly in the same groups. In the group treated with AG (group D), serum and tissue MDA and MPO levels and tissue iNOS expression were decreased while tissue ATPase levels were increased significantly. In group F, if AG was administrated before LPS, we observed that serum and tissue MDA and MPO levels and tissue iNOS expression were decreased while tissue ATPase levels were increased significantly. Thus, our study showed that AG had a protective effect when it was administrated before LPS, but it failed to prevent tissue iNOS expression and LP if there was established endotoxemia in OJ.