Amelioration of radiation-induced oxidative stress and biochemical alteration by SOD model compounds in pre-treated gamma-irradiated rats

INTRODUCTION: The role of metalloelements in tissue maintenance, function and response to injury offer a new approach to decreasing and/or treating radiation injury. We investigated the roles of CuL(2)SO(4), [MnL(2)O](2)Cl(4)(H(2)O)(2) and [(VL(2)O)(VL(2)H(2)O)]Cl(6) complexes (L=2-methylaminopyridine) of SOD-mimetic activities, in ameliorating the radiation-induced oxidative stress and alterations in some biochemical parameters in liver, kidney, spleen and brain in pretreated female rats exposed to gamma-irradiation. METHODS: Both untreated-rats and rats treated with the above complexes were subjected to whole-body gamma-irradiation (6 Gy). 5'-Nucleotidase (5'-NT), acetylcholinesterase (AChE), adenosne triphosphatase (ATPase), superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GSSG-R) were assessed as well as liver DNA and RNA contents and total protein concentration were estimated in tissue homogenates of the above organs. The same parameters were assessed in non-irradiated treated rats and normal control rats. Results were compared to irradiated non-treated and normal control rats. RESULTS: Pretreatment of gamma-irradiated rats with Mn(IV) or V(IV) complex produced a significant decrease in liver 5'-NT activity compared to the corresponding value of the untreated irradiated rats. In contrast, liver DNA and RNA contents and brain AChE and ATPase activities were significantly increased in irradiated rat group pre-treated with these metal complexes. Cu II, Mn IV or V IV complex inoculation prior to irradiation of normal rats exhibited a significant increase in SOD, CAT, GSSG-R activities and protein content of liver, kidney, spleen and brain homogenates compared with that of the untreated irradiated rats. The treatment of non-irradiated rats with these complexes produced a highly significant increase in mean activities of SOD and CAT, with no changes in other parameters vs. controls. CONCLUSIONS: Cu(II), Mn(IV) and V(IV) 2-methylaminopyridine complexes offer a physiological approach to ameliorate the radiation-induced biochemical alterations. In addition, they provide sufficient protection against radiation injury of radiosensitive tissues.     

Inhibition of matrix metalloproteinases by chemically modified tetracyclines in sepsis

Sepsis precipitates a systemic inflammatory stimulus that causes systemic release of cytokines and sequestration of polymorphonuclear neutrophils, resulting in degranulation of matrix metalloproteinases (MMPs), which causes extracellular matrix basement membrane degradation. One of the important anti-inflammatory properties of tetracyclines is their ability to inhibit MMPs. In this study, we focused on the regulation of MMPs in sepsis and their reduction by treatment with nonantimicrobial chemically modified tetracyclines (CMTs), which retain their anti-inflammatory activity. Sepsis was induced by cecal ligation and puncture (CLP) method. At 24 h and 1 h before CLP, some rats received CMT-3 (25 mg/kg), another group of rats received hydroxamate (H; an inhibitor of MMP; 25 mg/kg), and untreated rats received saline by gavage. At 0 h, 0.5 h, 1.5 h, and 24 h after CLP, blood and liver samples were collected. Plasma and liver MMP-9 by zymography and Western immunoblotting, plasma nitric oxide by measuring nitrate level, plasma glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) by enzymatic method, and liver gelatinase by radiolabeled gelatin lysis assay and 24 h mortality were determined. Plasma MMP-9 (92 kDa), nitrate, and GOT and GPT levels were elevated compared with the time 0 level and reached peak at 1.5 h CLP and remained high for 24 h. Both CMT-3 and H treatment reduced GOT,GPT, 92-kDa gelatinase, and nitrate levels throughout the 24 h. CMT-3 and H are equally effective in sepsis treatment. The 24-h mortality for CLP rats was 30%, whereas pretreatment with CMT-3 and H resulted in 0% mortality. Hepatic MMP-9 and gelatinase activity increased significantly after CLP, and pretreatment with CMT-3 and H inhibited these expressions. These results indicate the beneficial effect of CMT-3 in preventing the increase in GOT, GPT, NO, MMP-9, gelatinase activity, and the ensuing septic shock.     

Blood levels of glutamate oxaloacetate transaminase are more strongly associated with good outcome in acute ischaemic stroke than glutamate pyruvate transaminase levels

Ischaemic stroke is associated with an excessive release of glutamate in brain. GOT (glutamate-oxaloacetate transaminase) and GPT (glutamate-pyruvate transaminase) are two enzymes that are able to metabolize blood glutamate facilitating the lowering of extracellular levels of brain glutamate. Our aim was to study the association between blood levels of both enzymes and stroke outcome in patients with acute ischaemic stroke. We prospectively studied 365 patients with first ischaemic stroke<12 h. Glutamate, GOT and GPT levels were determined in blood samples obtained at admission. We considered functional outcome at 3 months [good outcome: mRS (modified Rankin Scale)≤2; poor outcome mRS >2], END (early neurological deterioration) in the first 72 h [increment ≥4 points in NIHSS (National Institutes of Health Stroke Scale)] and infarct volume [CT (computed tomography) at 36-72 h] as end points. We have found an inverse correlation between GOT and GPT levels and blood glutamate levels. Patients with poor outcome showed lower levels of GOT (11.9±8.2 compared with 22.7±10.2 m-units/ml, P<0.0001) and GPT (19.5±14.3 compared with 24.7±20.3 m-units/ml; P=0.004). A negative correlation has been found between GOT (Pearson coefficient=-0.477, P<0.0001) and GPT (Pearson coefficient=-0.116; P=0.027) levels and infarct volume. Patients with END showed higher levels of blood glutamate (381.7±97.9 compared with 237.6±114.0 μmol/l, P<0.0001) and lower levels of GOT (10.8±6.7 compared with 18.1±10.8 m-units/ml; P<0.0001). This clinical study shows an association between high blood GOT and GPT levels and good outcome in ischaemic stroke patients, this association being stronger for GOT than GPT levels.     

Serum glutathione S-transferase activity in liver diseases

Assay conditions of human liver glutathione S-transferase and its activity in human serum from liver disease patients were investigated. One mmol/l reduced glutathione, and 1 mmol/l-1-chloro-2,4-dinitrobenzene, pH 6.5, were used for the measurement, because of the very low non-enzymatic conjugation. Glutathione S-transferase activity was inhibited by bilirubin, but this inhibition was counteracted by the presence of a low concentration of albumin. The normal human serum glutathione S-transferase activity was 5.2 +/- 2.4 I.U./l (mean +/- S.D.), and was not influenced by any differences of age, sex or leukocyte count. A significant increase in serum enzyme activity was noted in cases of acute hepatitis with GPT exceeding 200 I.U./l, primary hepatoma and metastatic liver cancer. Some of the cases with fulminant hepatitis showed extremely high values. The degree of correlation between serum glutathione S-transferase and GOT or GPT was high in acute hepatitis, with GOT or GPT exceeding 200 I.U./l, in fulminant hepatitis, primary hepatoma and gall stones, while in chronic hepatitis and liver cirrhosis it was low. In cases of acute hepatitis and fulminant hepatitis, the disappearance of serum glutathione S-transferase from the blood was much faster than that of GOT and GPT. Serum glutathione S-transferase measurements will provide new and unique information for the diagnosis of acute liver diseases.     

Inhibition of Matrix Metalloproteinase on Hepatic Transforming Growth Factor β1 and Caspase-3 Activation in Hemorrhage

Objectives: Hemorrhage initiates an inflammatory response that induces the systemic release of cytokines and sequestration of polymorphonuclear neutrophils. Sequestered polymorphonuclear neutrophils release proteases, including matrix metalloproteinases (MMPs) that degrade elements of the extracellular matrix, contributing to the morbidity and mortality seen from hemorrhage. Activation of MMPs may be associated with changes in transforming growth factor β1 (TGF‐β1) and caspase‐3 signaling pathways. In this study, the authors examined hemorrhage‐induced changes in the expression of rat hepatic MMP‐9, tissue inhibitor of metalloproteinase‐1 (TIMP‐l), TGF‐β1, and caspase‐3 activities in the presence and absence of the MMP inhibitor hydroxamate. Methods: Hemorrhagic shock was induced in fasted, anesthetized, and cannulated rats by rapid phlebotomy to a mean arterial pressure level of 40 mm Hg, maintained for 90 minutes by withdrawal and infusion of blood, followed by a resuscitation period of lactated Ringer's infusion. Rats received either hydroxamate (25 mg/kg) or vehicle by gavage before hemorrhage. Twenty‐four hours after resuscitation, plasma and liver samples were collected. Liver MMP‐9, TGF‐β1, and caspase‐3 levels were quantified by Western immunoblotting. Plasma glutamic oxaloacetic transaminase (GOT) and plasma glutamic pyruvic transaminase (GPT) were determined enzymatically. Results: Plasma GOT, plasma GPT, and liver MMP‐9, TGF‐β1, and caspase‐3 levels were all significantly elevated at 24 hours postresuscitation when compared with the control values. Hepatic TIMP‐1, an in vivo inhibitor of MMP‐9, was unaltered at 24 hours. Hydroxamate treatment reduced GOT, GPT, MMP‐9, TGF‐β1, and caspase‐3 levels at 24 hours. The mortality of hemorrhaged untreated rats was 29% after 24 hours, and pretreatment with hydroxamate reduced mortality to 0%. Conclusions: These results indicate the beneficial effects of MMP inhibitor in preventing an increase in GOT, GPT, MMP‐9, TGF‐β1, and caspase‐3 activity with the potential for improvement of hepatic injury due to hemorrhage.     

Fluvastatin ameliorates endotoxin induced multiple organ failure in conscious rats

OBJECTIVES: Sepsis is a severe inflammatory disorder that may lead to multiple organ failure. Lipopolysaccharide (LPS) is associated with Gram-negative sepsis and can activate monocytes and macrophages to release pro-inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO) and anti-inflammatory mediator such as interleukin-10 (IL-10). In this present study, we used fluvastatin, a HMG-CoA reductase inhibitor, to study its effects upon LPS-induced endotoxic shock in conscious rats. METHODS: The experiments were designed that rats received an intravenous injection of 1mg/kg fluvastatin followed 10min later, by an intravenous injection of 10mg/kg Klebsiella pneumoniae LPS, the latter inducing endotoxic shock amongst conscious rats. Subsequently, the levels of certain biochemical variables and cytokines in serum were then measured during the ensuing 48-h period following sepsis. These included total cholesterol (TCH), triglyceride (TG), blood urea nitrogen (BUN), creatinine (Cre), creatine phosphokinase (CPK), lactic dehydrogenase (LDH), aspartate transferase (GOT), alanine transferase (GPT), tumor necrosis factor-alpha, interleukin-10 and nitric oxide. RESULTS: LPS significantly increased blood TG, BUN, Cre, LDH, CPK, GOT, GPT, TNF-alpha, IL-10 and NO levels but decreased the blood TCH level. Pretreatment of test rats with fluvastatin decreased blood levels of certain markers of organ injury, suppressed the release of TNF-alpha and increased IL-10, and NO levels following LPS treatment. Fluvastatin did not affect the blood TCH and TG level subsequent to the development of sepsis. CONCLUSIONS: Pre-treatment with fluvastatin suppresses the release of plasma TNF-alpha, increases plasma IL-10, and NO production, and decreases the levels of markers of organ injury associated with endotoxic shock, so ameliorating LPS-induced organ damage amongst conscious rats.     

丙溴磷对家兔肝组织脂质过氧化及肝功能的影响

背景丙溴磷为有机磷酸酯类农药杀虫剂,以往对其毒性的研究主要集中在胆碱酯酶的抑制上,而丙溴磷对脂质过氧化及肝功能影响的研究尚较少.目的探讨丙溴磷对肝组织脂质过氧化及肝功能的影响.设计完全随机对照的实验研究.地点、材料和干预本实验在济宁医学院职业卫生与环境医学研究所毒理研究室完成.实验选择3.5月龄的健康家兔42只,雌雄各半.采用随机数字表法将家兔分为高剂量组[染毒剂量为0.08 g/(kg·d)]、低剂量组[染毒剂量为0.02 g/(kg·d)]、丙酮对照组3个组,高、低剂量组每组12只,丙酮对照组18只(给予1 mL/d丙酮).测定染毒前、染毒后5,10 d家兔血清谷草转氨酶(glutamic oxalacetic transaminase enzyme,GOT),谷丙转氨酶(glutamic-pyruvic transaminase enzyme,GPT)活力;分别对染毒前取对照组6只白兔、染毒后5 d在3组各取6只家兔、染毒后10 d取各组剩余的白兔,进行肝组织中谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、超氧化物歧化酶(superoxide dismutase,SOD)的测定.主要观察指标各组家兔肝组织脂质过氧化指标及肝功能指标.结果高、低剂量组白兔染毒后5,10 d的GSH-Px,GPT,GOT,SOD活力均显著高于丙酮对照组染毒前和处于相同染毒时间的丙酮对照组(t=2.746～10.087,P＜0.01);高剂量组染毒后5 d肝组织GSH-Px,GPT,GOT,SOD活力[(1 275.6±138.2),(811.3±111.9),(1 310.3±127.4),(943.0±104.0)nkat/gl显著高于同时间低剂量组[(1 051.0±124.4),(663.8±97.2),(657.6±93.8),(734.6±99.4)μkat/L](t=2.788～10.105,P＜0.01);高剂量组染毒后10d肝组织GSH-Px,GPT,GOT,SOD活力显著高于同时间低剂量组(t=2.792～7.439,P＜0.01).结论丙溴磷使家兔肝组织脂质过氧化增强,可能是丙溴磷致肝功能受损的机制之一.     

Cell phenotype specific kinetics of expression of intratracheally injected manganese superoxide dismutase-plasmid/liposomes (MnSOD-PL) during lung radioprotective gene therapy

Intratracheal (IT) injection of manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) complexes prior to whole lung irradiation of C57BL/6J mice provides significant protection from acute and chronic irradiation damage. We determined the duration of increased MnSOD biochemical activity and differential expression of a hemagglutinin (HA) epitope-tagged MnSOD transgene. HA-MnSOD-PL was IT injected at doses of 0-1000 microg, and mice were killed 1,2,3 or 4 days later. Other groups of mice were irradiated to 20 Gy to the pulmonary cavity 24 h after injection and killed at the same time points as non-irradiated mice. Both non-irradiated and irradiated groups of mice showed increased MnSOD biochemical activity with plasmid dose that plateaued at 100 microg of MnSOD plasmid DNA. In control mice, MnSOD biochemical activity decreased at 2, 3 or 4 days after injection. In irradiated mice, MnSOD biochemical activity decreased at day 2 but increased on days 3 and 4. HA-MnSOD expression decreased in broncheoalveolar macrophages and alveolar type-II cells 3 days after injection in non-irradiated and irradiated mice, but remained elevated in endothelial and epithelial cells past 4 days. The data provide a rationale for every second-day administration of intrapulmonary MnSOD-PL in clinical trials of radioprotective gene therapy. This should be sufficient to provide radioprotection during radiation treatments.     

献血45d后献血者部分生化和免疫指标变化的研究

目的分析无偿献血者献血后部分生化免疫参数的变化及其对机体功能恢复能力的影响。方法选择生活、工作环境相同,饮食种类和运动量基本一致的献血者250名,年龄18—26岁,按血液采集标准步骤采集外周静脉血,分别测定其总蛋白、白蛋白、总淋巴细胞(CD3)、T辅助细胞(CD4)和T抑制细胞(CD8)浓度(数),45d后再次采集血液测定相同参数并进行比较。结果与献血前比较,所测定的献血后外周血中的生化指标变化无统计学意义(P>0.05);血液中总蛋白和白蛋白浓度均在正常范围内,与献血前比较其浓度明显增加(P<0.05);四色流式细胞仪检测显示,献血后CD3、CD4和CD8均显著增高(P<0.01),CD4/CD8比值变化无统计学意义(P>0.05);此外,还显示献400ml者的总蛋白、白蛋白和总淋巴细胞数有高于献200ml者的趋势。结论献血能启动献血者机体应激反应系统,蛋白合成增加,T细胞亚群比例升高,使机体进入新的平衡状态。     

绿原酸对糖尿病大鼠肾脏氧化应激作用的实验研究

目的 探讨绿原酸对糖尿病大鼠肾脏氧化及抗氧化系统的影响.方法 将36只大鼠随机分成N组(正常组)、DM组(糖尿病组)及CA组(绿原酸干预组).DM组和CA组造糖尿痛模型,分别给予腹腔注射生理盐水和绿原酸,饲养10周后,测定血糖、肾脏重量、体重变化,肾皮质超氧化物歧化酶(SOD)、谷胱甘肽过氧化酶(GSH-PX)、丙二醛(MDA)含量及尿微量白蛋白排泄率(UAER).结果 与DM组大鼠相比,CA组大鼠血糖无明显差别,而肾重、体重明显增加,肾皮质SOD、GSH-PX活性明显上升,MDA含量及UAER则明显减少(均P<0.05).结论 绿原酸有改善糖尿病大鼠的一般状况,提高抗氧化能力,抑制氧化应激.减少尿蛋白的作用.     

Relationship of serum enzyme activities to demographic variables in a healthy population

Estimations of 6 serum enzyme activities were carried out in 519 subjects rigorously screened to exclude overt and latent disease, and obesity. The mean values of AP, GOT and GPT, and CPK were higher in males than in females. A negative correlation between age and activities of GPT and CPK was observed in males, whereas in females all activities measured, except that of GPT, showed a positive correlation with age. Only 5N and HBD failed to demonstrate a positive correlation with total body weight in one or other sex. A positive correlation between social class and AP was noted in females, and some significant correlations between diastolic blood pressure and some enzyme activities were found, but no association between enzyme activity and smoking habit could be detected.Computer programs were used to generate equations expressing enzyme activity as a function of age, total body weight, social class and diastolic blood pressure for each sex independently. From these, sets of reference values were derived which encompassed 95% of the demographically-corrected values for this healthy population. A trial of AP in medical out-patient clinics, and of 3 enzymes in cases of myocardial infarction, suggested that demographically-corrected reference values for serum enzymes may be more accurate than conventional parametric normal ranges in confirming or excluding organic disease.     

Effects of bis(alpha-furancarboxylato)oxovanadium(IV) on non-diabetic and streptozotocin-diabetic rats

BACKGROUND: Bis(alpha-furancarboxylato)oxovanadium(IV) (BFOV), a new orally active anti-diabetic vanadium complex with organic agent, has been synthesized and characterized. The current study examined the stability in aqueous solution and effects of the complex on carbohydrate and lipid metabolism in non-diabetic and streptozotocin-induced diabetic rats. METHODS: Diabetic rats were induced by a single dose injection of streptozotocin (STZ, 50 mg/kg body weight, i.p.). The rats were randomly divided into non-diabetic (control, CON), diabetic (DM) and BFOV (0.2 mmol/kg body weight)-treated, diabetic-BFOV (0.1, 0.2 and 0.4 mmol/kg body weight) groups. All substances were given intragastrically to non-diabetic and STZ-induced diabetic rats for 4 weeks. Blood glucose concentration was monitored during administration and, at the end of experiment glycosylated hemoglobin, serum insulin, lipid concentrations and glycogen content were observed. RESULTS: Administration of BFOV to STZ-diabetic rats dose-dependently reduced blood glucose concentration when compared to diabetic rats (P<0.01), but it did not influence blood glucose in non-diabetic rats. Serum insulin concentrations were not increased in the BFOV-treated diabetic groups and, in contrast, significantly lowered in the 0.2 mmol/kg body weight BFOV-treated non-diabetic group at the end of experiment. Moreover, BFOV markedly reduced glycosylated hemoglobin concentration and improved dyslipidemia in STZ-diabetic rats, in a dose-dependent manner (P<0.05, P<0.01), but had no significant effect on non-diabetic rats. CONCLUSION: The organic vanadium complex was found to effectively attenuate diabetic alterations in STZ-diabetic rats.     

肉毒素和肿瘤坏死因子对大白鼠肝功能的影响

１MaterialsandMethods１．１ExperimentalanimalsSDmaleratswiththeageof１monthproducedinShanghai，weightedfrom９０gto１００g．１．２MainreagentsandinstrumentsDMEMmedium（providedbyGIBCOcompanyofUSA），０．０３％collagenaseⅠsolutions５０ml（SigmaCorporation，withDMEMassolvent），phosphoricbuffersolution（PBS）２５０ml，RDB－７８peristalsispump（InstrumentCorporationofZhangjiaganginJiangsu），cen－trifugalapparatusofBiofuge１５R，productionofGermanycompa－ny．１．３Separationandcultu…     

Elevation of glutamic pyruvic transaminase and gamma-glutamyl transpeptidase in obesity

Study was made of glutamic pyruvic transaminase (GPT), glutamic oxalacetic transaminase (GOT), and gamma-glutamyl transpeptidase (gamma-GTP) in 729 obese subjects in various groups, namely, primary school children, high school children, university students, and outpatients. The incidences of abnormal GPT, GOT, and gamma-GTP in the obese subjects were frequently significantly higher than in the controls. It was most clearly shown in GPT. The incidences of abnormal GPT in the obese females were significantly lower than those in the obese males, but were significantly higher than the controls. Higher incidences of abnormality in the school children were ascribed to the higher degree of obesity in the children. The extent of increase in GPT was considerable. GPT was sometimes higher than 6 times the normal upper limit.     

Alterations in the enzyme profile in intensive care patients undergoing total parenteral nutrition.

Total parenteral nutrition (TPN) has been demonstrated to be an effective therapeutic means in improving the clinical course of the critically ill patients. Various metabolic complications are described; the cause of some of these remain unclear. The changes in some plasma enzyme indices (GOT, GPT, GIDH, LDH, HBDH, CPK, ChE, AP, gamma-GT) in two groups of critically ill patients undergoing TPN (group with more marked enzyme alterations and group with less marked alteration) were examined. Two types of alterations were found: (1) early increase of some enzymes (GOT, GPT, GIDH); (2) constant increase of plasma enzyme level during TPN (AP, gamma GT). These two evolutionary patterns were more evident in the complicated group and the enzyme changes were statistically significant for GOT and GPT (P = 0.05) and not significant for initial values of G1DH, ap and gamma-GT. Both groups presented constant elevated plasma values of LDH, HBDH, CPK and depressed constant ChE value during treatment; the difference was not significant in both groups for the same enzymes. The data were interpreted from a functional point of view; that is they were related to both the metabolic post-aggressive state and TPN. A relationship between the rate of protein catabolism and the inductive increase of some enzymes (GOT, GPT, G1DH) was found. Whereas a final induction in the energy metabolism is suggested for other enzymes (LDH, HBDH), the alteration of CPK, AP, gamma-GT and ChE was interpreted as dependent on: (1) direct muscular trauma (CPK); (2) functional increase in relation to the duration of TPN (AP and gamma-GT); (3) possible depressed malnutritive synthesis (ChE). The improvement of the enzymatic patterns with the early use of TPN and with the improvement of clinical and nutritional conditions was emphasized.     

构建高脂饮食肥胖大鼠模型体质量及代谢变化与天麻素的干预

背景:天麻素广泛应用于眩晕、头痛及高血压等的辅助治疗,其作为干预物质用于高脂肥胖大鼠的治疗有待评估.目的:构建不同浓度天麻素对高脂饮食性肥胖大鼠模型,观察其对体质量与血清代谢物水平的影响,分析其可能的作用机制.设计:随机对照动物实验.单位:兰州大学基础医学院生理与心理研究所.材料:实验于2007-06/2007-08在兰州大学基础医学院生理与心理研究所和甘肃省新药临床前研究重点实验室完成.选用44只生后1周雄性健康SD大鼠,体质量(99.57±2.13)g,由中科院上海斯莱克实验动物有限公司提供.实验过程中对动物的处置符合动物伦理学标准.基础饲料由苏州双狮实验动物饲料科技有限公司生产,高脂饲料由本实验室自行配制.每100克含基础饲料57.5 g、蛋黄粉11.79g、猪油10g、猪胆盐0.2g、酪蛋白7g、奶粉13g、食盐0.085g、酵母粉0.425g;其中含脂肪22.07g、蛋白质23.7g、碳水化合物39g、热量472.16千卡.纯度为98%的天麻素购自陕西旭煌植物科技开发公司.丙二醛和总抗氧化能力试剂盒均为南京建成生物工程研究所生产.方法:构建天麻素干预高脂饮食性肥胖大鼠模型:①采用基础饲料适应喂养大鼠1周,随机数字表法将大鼠分为正常对照组(n=10)、高脂组(n=10)、高脂 天麻素低、中、高剂量组(每剂量组各8只).②正常对照组喂基础饲料,其它各组均喂高脂饲料.正常对照组和高脂组每天灌胃0.9%生理盐水0.3 mL,高脂 天麻素低、中、高组灌胃同等容量浓度分别为15,30,60mg/(kg·d)的天麻素溶液.③各组大鼠自由进食和饮水,共8周.主要观察指标:①每周末检测各组大鼠体质量.②每日上午定时记录大鼠摄入热量.③高脂喂养结束后,于大鼠股动脉取血测血糖值,同时检测血清丙二醛、总抗氧化能力、胰岛素、游离脂肪酸,血脂、谷丙转氨酶及谷草转氨酶水平,并计算胰岛素敏感指数和抵抗指数.结果:大鼠44只均进入结果分析.①体质量:高脂喂养4～8周高脂组大鼠体质量明显高于正常对照组,差异有显著性意义(P＜0.001).天麻素各剂量组体质量均低于高脂组,差异有显著性意义(P＜0.05～0.01),高脂 天麻素低、中、高剂量组组间比较,差异无显著性意义(P＞0.05),提示天麻素抑制大鼠高脂饮食肥胖无剂量相关性.②摄入热量:高脂组大鼠高于正常对照组,差异有显著性意义(P＜0.01).高脂饮食4周后天麻素各剂量组均低于高脂组,差异有显著性意义(P＜0.05～0.01).③血清丙二醛、总抗氧化能力、谷丙转氨酶、谷草转氨酶水平:与正常对照组相比,高脂组的总抗氧化能力下降,丙二醛水平上升,谷丙转氨酶水平增加,差异均有显著性意义(P＜0.01).与高脂组相比,天麻素低剂量组的总抗氧化能力明显上升,丙二醛水平下降,差异均有显著性意义(P＜0.01).④胰岛素及血糖水平:与正常对照组比较,高脂组大鼠血糖浓度升高,胰岛素敏感指数下降,抵抗指数上升,差异有显著性意义(P＜0.05～0.01).与高脂组比较,天麻素低剂量组血糖浓度降低,胰岛素敏感指数升高,胰岛素抵抗指数降低,差异均有显著性意义(P＜0.05～0.01).⑤游离脂肪酸及血脂水平:与正常对照组比较,高脂组大鼠的游离脂肪酸、低密度脂蛋白胆固醇升高,高密度脂蛋白胆固醇降低,差异有显著性(P＜0.05～0.01).结论:天麻素可抑制高脂饮食性肥胖大鼠体质量增加,作用机理可能与其调节葡萄糖和游离脂肪酸代谢、改善胰岛素抵抗和提高抗氧化能力有关.     

The effects of hemodialysis on blood glutamate levels in chronic renal failure: Implementation for neuroprotection

Purpose

The purpose of the present study is to investigate whether hemodialysis (HD) is effective in lowering blood glutamate levels. In addition, we examined the effect of HD on glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) levels in the blood and described the rate and pattern of blood glutamate clearance during HD.

Materials and Methods

Blood samples were taken from 45 patients with stage V chronic kidney disease immediately after initiation of HD and hourly, for a total of 5 blood samples. Samples were sent for determination of glutamate, glucose, GOT, GPT, hemoglobin, hematocrit, urea, and creatinine levels. A blood sample from 25 healthy volunteers without chronic renal failure was used as a control for the determination of baseline blood levels of glutamate, GOT, and GPT.

Results

Glutamate and GPT levels in patients on HD were higher at baseline compared with healthy controls (P < .001). In the first 3 hours after HD, there was a decrease in blood glutamate levels compared with baseline levels (P < .00001). At the fourth hour, there was an increase in blood glutamate levels compared with the third hour (P < .05).

Conclusions

Hemodialysis may be a promising method of reducing blood glutamate levels.     

Superoxide dismutase mimetic preserves the glomerular capillary permeability barrier to protein

Overproduction of superoxide (O2*) occurs in glomerular disease and may overwhelm the capacity of superoxide dismutase (SOD), thereby intensifying oxidant injury by O2* and related radical species that disrupt the glomerular capillary permeability barrier to protein. We examined the efficacy of the SOD mimetic tempol in preserving glomerular permeability to protein using 1) a rat model of glomerular immune injury induced by an antiglomerular basement membrane antibody (anti-GBM), and 2) isolated rat glomeruli in which injury was induced by the cytokine tumor necrosis factor-alpha (TNFalpha). To induce glomerular immune injury, rats received anti-GBM using a protocol that results in prominent infiltration of glomeruli by macrophages and in which macrophage-derived TNFalpha has been shown to mediate albuminuria. To increase glomerular capillary permeability to albumin (P(alb)) ex vivo, isolated glomeruli were incubated with TNFalpha at concentrations (0.5-4.0 microg/ml) known to stimulate O2* production. Increments in P(alb) were detected by measuring changes in glomerular volume in response to an applied oncotic gradient. Significant increases in the urine excretion of albumin and F(2alpha)-isoprostane were observed in rats with glomerular immune injury without a significant change in systolic blood pressure. Tempol treatment significantly reduced urine isoprostane and albumin excretion. In isolated glomeruli, TNFalpha increased P(alb) and tempol abrogated this effect, both in a dose-dependent manner. These observations indicate that SOD mimetics can preserve the glomerular permeability barrier to protein under conditions of oxidative stress from O2* production.     

血糖和血脂波动对糖尿病大鼠肾脏组织氧化应激、周围神经病变以及认知功能的影响

目的分析血糖和血脂波动对糖尿病大鼠肾脏组织氧化应激、周围神经病变以及认知功能的影响。方法将无特定病原体(SPF)级雄性SD大鼠按照随机数字表法分成空白对照组(NC组)、持续高血糖组(GH组),血糖波动组(GF组)、持续高血糖血脂组(GLH组)和血糖血脂波动组(GLF组),每组各10只。经腹腔注射链脲佐菌素建立糖尿病大鼠模型,经腹腔注射葡萄糖液和胰岛素制备糖尿病血糖波动大鼠模型,经腹腔注射泰洛沙泊制备持续高血糖血脂模型,经腹腔注射葡萄糖液、泰洛沙泊、胰岛素和血脂康制备糖尿病血糖血脂波动大鼠模型,NC组注射等量0.9%氯化钠溶液。每周固定1 d检测大鼠体重,血糖、血脂波动12周后,检测大鼠血糖相关指标[最大血糖波动幅度(LAGE)、平均血糖波动幅度(MAGE)、全天血糖水平的标准差(SDBG)]、血脂相关指标[胆固醇最大波动幅度(MFC)、胆固醇平均值(MC)、胆固醇标准差(SDC)、甘油三酯最大波动幅度(MFT)、甘油三酯平均值(MT)和甘油三酯标准差(SDT)]、糖化血糖蛋白(HbA1c)、氧化应激[超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)]、认知功能和坐骨神经运动传导速度(MNCV)。结果初始大鼠体重差异无统计学意义(P> 0.05)。血糖、血脂波动12周后,与NC组相比,GH组、GF组、GLH组及GLF组大鼠体重、SOD活力、GSH水平、穿越平台次数显著降低,逃避潜伏期、潜伏期距离及血糖相关指标、HbA1c、血脂相关指标、MDA水平显著升高,MNCV显著减慢,差异有统计学意义(P <0.05)。与GH组相比,GF组大鼠体重、血糖相关指标、HbA1c、血脂相关指标、SOD活力、GSH水平及穿越平台次数明显降低,MDA水平、逃避潜伏期、潜伏期距离明显升高,MNCV显著减慢,差异有统计学意义(P <0.05)。与GLH组相比,GLF组大鼠体重、血糖相关指标、HbA1c、血脂相关指标、SOD活力、GSH水平及穿越平台次数明显降低,MDA水平、逃避潜伏期、潜伏期距离明显升高,MNCV显著减慢,差异有统计学意义(P <0.05)。结论血糖、血脂波动可以使大鼠周围神经病变和认知功能障碍加重,其机制可能与氧化应激损伤增高有关。     

缺血预处理预防肝细胞分离过程中的缺血再灌注损伤

背景：缺血预处理能否减轻肝细胞分离过程中的缺血再灌注损伤及改善供体残留肝脏功能？经检索国内外罕见这方面的研究。目的：探讨缺血预处理对分离肝细胞及供鼠残肝缺血再灌注损伤的防治作用。方法：12只SD大鼠随机分为2组：单纯肝部分切除组和缺血预处理组,各6只。采用改良四步胶原酶灌注法分离上述切除肝脏肝细胞,同时收集术前和术后1d大鼠的血清。结果与结论：缺血预处理组切除肝脏分离肝细胞成活率、增殖活性及白蛋白合成、超氧化物歧化酶水平显著高于单纯肝部分切除组（P〈0.05）,而乳酸脱氢酶、谷丙转氨酶、丙二醛水平显著减少（P〈0.05）;与单纯肝部分切除组比较,缺血预处理组大鼠血清白蛋白、乳酸脱氢酶、谷丙转氨酶、超氧化物歧化酶、丙二醛水平差异无显著性意义（P均〉0.05）。结果表明缺血预处理能减轻肝细胞分离过程中的缺血再灌注损伤,其机制可能与其自身缺血性预适应、抗氧化、清除氧自由基的能力相关,但对供鼠肝部分切除后残肝功能的影响不明显。