乐果对大鼠皮层神经元氧化损伤及兴奋性氨基酸递质含量的影响

目的 观察乐果染毒对原代培养的大鼠皮层神经元的的毒性作用及损伤机制.方法 体外原代培养SD大鼠皮层神经元6 d后,加入终浓度为1、5、10、50、100 μmol/L的乐果,于染毒后48 h收获细胞,取匀浆上清液用于氧化损伤及细胞内兴奋性氨基酸递质的测定,流式细胞术检测细胞凋亡.结果 染毒48 h后,乐果浓度在5、10、50、100 μmol/L时,超氧化物歧化酶(SOD)活力[(1.04±0.02)、(0.99±0.02)、(0.96±0.02)、(0.91±0.02)U/mg pro]即明显降低,谷胱甘肽(GSH)含量[(219.35±6.79)、(205.6±6.29)、(194.06±2.63)、(93.68±7.56)mg/g pro]明显降低,丙二醛(MDA)含量[(21.22±0.29)、(24.01±0.34)、(27.15±1.02)、(32.91±1.39)nmol/mg pro]明显升高,与对照组比较,差异均有统计学意义(P<0.01);10、50、100 μmol/L剂量组天冬氨酸含量明显升高,1、5、10、50、100μmol/L剂量组谷氨酸含鼍明显升高,与对照组比较,差异均有统计学意义(P<0.01);1、10、100 μmol/L染毒组乐果对神经无细胞凋亡影响明显.乐果染毒后,神经元内MDA含量与兴奋性氨基酸(天冬氨酸、谷氨酸)含量呈正相关,相关系数分别为0.937和0.759;而与GSH含量呈负相关,相关系数分别为-0.868和-0.801,有统计学意义(P<0.01).结论 乐果可引起神经元氧化损伤及兴奋性氨基酸递质含量变化,共同参与神经元的凋亡过程.     

氯丙烯亚慢性中毒大鼠血清脂质过氧化的时效关系

目的研究氯丙烯(AC)亚慢性中毒大鼠血清脂质过氧化的改变是否存在时间效应关系,探讨其中毒性神经病发病机制。方法选用90只Wistar雄性大鼠随机分为对照组(n=50)和染毒组(n=40),染毒组大鼠以200 mg/kg剂量AC经口灌胃,每周3次,分别在染毒第3、6、9和12周随机从对照组和染毒组取大鼠10只,用生物化学方法测定染毒组与相应时间对照组大鼠血清中丙二醛(MDA)、谷胱甘肽(GSH)含量、抗活性氧能力(anti-ROS)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、超氧化物岐化酶(SOD)和总抗氧化能力(T-AOC)活力等指标。结果随染毒时间的延长和步态评分的增加,MDA呈进行性升高趋势;anti-ROS、GSH、GSH-Px、CAT、SOD、T-AOC呈下降趋势。MDA从染毒第3周和步态评分2分开始升高,与对照组相比差异有统计学意义(P<0.05)。结论AC亚慢性染毒可引起大鼠血清发生脂质过氧化,并且存在明显的时间效应关系,脂质过氧化可能是AC诱导的神经毒性的发病机制之一;MDA改变的最早、最为敏感,可为AC中毒的早期诊断提供了依据。     

铈对大鼠脏器系数及肝肾抗氧化能力的影响

目的　探讨稀土元素铈 (Ce)对SD雌性、雄性大鼠的某些生物学效应。方法　采用动物解剖与生化检测相结合的方法 ,研究长期饮用不同剂量三硝酸铈溶液对大鼠各脏器系数及肝、肾超氧化物歧化酶(SOD)活力和丙二醛 (MDA)含量的影响。结果　与对照组相比 ,低、中、高剂量组雄性大鼠肺器系数均明显升高 ,分别为 (4 1± 0 8) ,(3 7± 0 4 ) ,(4 3± 1 5 )mg/ g ;低、中剂量组雌性大鼠肺器系数明显增加(P <0 0 5 ) ;低剂量组雌性大鼠肝脏重量明显增加 (33 2± 6 3)mg/ g ,而且铈对雌、雄两性大鼠作用的靶器官以及作用程度有所差异 ;各剂量组大鼠肝脏SOD活力均明显降低 ,分别为 (30 34 6± 5 6 6 6 ) ,(30 5 0 5± 4 5 6 3) ,(30 83 4± 5 6 0 3)U/ml,中、高剂量组大鼠肾脏SOD活力也明显下降 (P <0 0 5 ) ;但肝、肾MDA含量无明显变化。结论　稀土元素铈对大鼠具有较强的毒害作用 ,主要靶器官为肝脏和肺 ,并使肝、肾抗氧化能力降低     

大鼠进行性被动性Heymann肾炎模型建立及其发病机制

目的 观察进行性被动性Heymann肾炎（ppHN）模型大鼠的肾损害并初步探讨其发病机制。方法 利用兔抗大鼠BBM抗血清多次免疫建立ppHN模型。检测实验第1、3、6、8周末24h尿蛋白、血清生化指标及超氧化物歧化酶（SOD）和丙二醛（MDA）水平,观察肾组织病理改变。结果 ppHN大鼠24h尿蛋白量进行性升高,血清SOD水平明显低于对照组,MDA水平明显高于对照组;肾脏病理改变为肾小球毛细血管基底膜增厚,上皮下免疫复合物沉积和足突融合。结论 ppHN是研究人类膜性肾病理想的动物模型,脂质过氧化损伤可能是导致肾损害的重要原因。     

葛根素对异丙肾上腺素诱导小鼠心肌纤维化的保护作用

目的探讨葛根素对异丙肾上腺素诱导的小鼠心肌纤维化的保护作用及其可能机制。方法将昆明种小鼠分为溶媒对照组、心肌纤维化模型组、葛根素低、高剂量(0.6、1.2 g.kg-1)组、卡托普利(25 mg.kg-1)组。预先ig给药3 d后,同时皮下注射5 mg.kg-1异丙肾上腺素1 d后,以2.5 mg.kg-1.d-1连续注射30 d。停止注射异丙肾上腺素后,再继续ig给药7 d。称重小鼠,取心脏称重,计算心重指数(CWI);消化法测定心肌羟脯氨酸(Hydro)的含量;Masson染色观察心肌纤维化的程度并计算心肌胶原容积分数(CVF);测定小鼠心肌匀浆中超氧化物歧化酶(SOD)、丙二醛(MDA)的含量。结果葛根素给药组与模型组比较均能降低CWI和Hydro的含量;Masson染色结果显示:葛根素给药组心肌细胞间的胶原含量明显减少,CVF明显下降;与模型组比较,葛根素给药组心肌匀浆中SOD水平增高,MDA含量下降。结论葛根素对异丙肾上腺素诱导的小鼠心肌纤维化有一定的预防作用,该作用与抑制胶原的形成、抗脂质过氧化及清除氧自由基有关。     

Effects of Some Antibiotics on Activity of Glucose-6-Phosphate Dehydrogenase from Human Erythrocytes In Vitro and Effect of Isepamicin Sulfate on Activities of Antioxidant Enzymes in Rat Erythrocytes

The purpose of this study was to investigate effects of some antibiotics on glucose-6-phosphate dehydrogenase (G6PD), antioxidant enzymes, and malondialdehyde (MDA). Initially, for in vitro studies, G6PD was purified from human erythrocyte, 9811-fold in a yield of 42.4% by using ammonium sulfate precipitation and 2′,5′ ADP-Sepharose 4B affinity gel. The purified enzyme showed a single band on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The effects of four different antibiotics (isepamicin sulfate, meropenem, chloramphenicol, and thiamphenicol glisinat hydrochloride) were investigated on the purified enzyme. K_i value and type of inhibition were determined by means of Lineweaver–Burk graphs and regression analysis graphs. Isepamicin sulfate inhibited the enzyme activity (I₅₀ value, 2.1 mM; K_i value, 1.7 mM), whereas thiamphenicol glisinat hydrochloride activated the G6PD dose dependently. Other drugs showed no inhibition and activation effect. In addition, the effects of isepamicin sulfate on the activities of G6PD, glutathione reductase (GR), superoxide dismutases (SOD), glutathione peroxidase (GPx), catalase (CAT), and glutathione S-transferase (GST) and MDA contentrations were examined in Sprague-Dawley rat erythrocytes in vivo. A marked alteration in the activities of these enzymes and MDA levels may be the result of oxidative stress in the rats receiving isepamicin sulfate.     

Levels of paraoxonase,an index of antioxidant defense,in patients with active sarcoidosis

ABSTRACT

Objective: Oxidative mechanisms are currently discussed as playing a crucial role in the genesis of inflammatory lung diseases. We aimed to evaluate the oxidant–antioxidant balance in the pathogenesis and activity of sarcoidosis and to search if the change in the level of PON can be taken as an activity marker.

Methods: 26 active sarcoidosis subjects aged 41.3?±?12.9 years, 37 inactive subjects aged 39.6?±?11.7 years and 48 control subjects aged 48.9?±?2.5 years were recruited in our study. Malondialdehyde (MDA), paraoxonase1 (PON1) and oxidized low density lipoprotein (oxLDL) levels in serum were analyzed by spectrophotometric, kinetic, and ELISA methods, respectively.

Results: PON1 levels were significantly lower in the active disease state than both the inactive form and control groups. MDA levels were significantly higher in active sarcoidosis than both the inactive disease and control groups, and oxLDL levels were significantly higher in the active disease group than the inactive group and control group. The level of PON1 in the inactive disease group is not significantly different from the control group while the oxLDL and MDA levels of inactive group is significantly higher than the control group (p?<?0.001). There was a negative correlation between the PON1 activities and MDA values in both active and inactive groups (p?=?0.008).

Conclusion: Oxidative stress increases in sarcoidosis might be due to both increase in lipid peroxidation and decrease in antioxidant status (PON1) and the relationship between oxidative status and the activation of the disease should be discussed by comparing the previously known activation criteria.     

TESTICULAR GAMETOGENIC AND STEROIDOGENIC ACTIVITIES IN CYCLOPHOSPHAMIDE TREATED RAT: A CORRELATIVE STUDY WITH TESTICULAR OXIDATIVE STRESS

ABSTRACT

The present work examined the changes in testicular activities in relation to testicular oxidative stress in cyclophosphamide as well as human chorionic gonadotrophin (hCG) co-treated cyclophosphamide treated Wistar strain rats. Testicular activities were evaluated by the quantification of spermatogenesis and by the measurement of steroidogenic key enzyme activities along with plasma levels of testosterone. Testicular oxidative stress in relation to cyclophosphamide treatment was monitored by the study of products of free radicals like conjugated dienes and malondialdehyde (MDA) as well as the activity of testicular antioxidant enzymes like peroxidase and catalase. Cyclophosphamide treatment at the dose of 5 mg/kg body weight/day for 28 days resulted a significant diminution in the activities of testicular Δ⁵, 3β-hydroxysteroid dehydrogenase (Δ⁵, 3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD) activities, plasma level of testosterone along with significant reduction in the number of germ cells at stage-VII of spermatogenesis. Levels of testicular MDA and conjugated dienes both were elevated whereas testicular peroxidase and catalase activities both were inhibited significantly in cyclophosphamide treated rats in comparison to control. After hCG co-administration at the dose of 5 I.U./kg body weight/day for 28 days in cyclophosphamide treated rats resulted a significant protection in the activities of testicular peroxidase and catalase along with significant decrease in the levels of MDA and conjugated dienes to the control level. Moreover, the testicular steroidogenic key enzyme activities and spermatogenesis along with plasma levels of testosterone were restored to the control level. Therefore, it may be concluded that there is a correlation between testicular steroidogenic activities as well as spermatogenesis and testicular oxidative stress in cyclophosphamide treated rats. Moreover, as restoration of plasma testosterone to the control level is noted in hCG co-treated cyclophosphamide treated rat, therefore, the results suggest that testosterone may be the key regulator for this correlation.     

Antiepileptogenic effect of curcumin on kainate-induced model of temporal lobe epilepsy

Abstract

Context: Temporal lobe epilepsy (TLE) is an intractable neurological disorder. Curcumin is the bioactive component of turmeric with anti-epileptic and neuroprotective potential.

Objective: The beneficial effect of curcumin on the intrahippocampal kainate-induced model of TLE was investigated.

Materials and methods: Rats were divided into sham, curcumin-pretreated sham, kainate and curcumin-pretreated kainate groups. The rat model of TLE was induced by unilateral intrahippocampal injection of 4?μg of kainate. Rats received curcumin p.o. at a dose of 100?mg/kg/d starting 1 week before the surgery. Seizure activity (SE) and oxidative stress-related markers were measured. Furthermore, the Timm index for evaluation of mossy fiber sprouting (MFS) and number of Nissl-stained neurons were quantified.

Results: All rats in the kainate group had SE, while 28.5% of rats showed seizures in the curcumin-pretreated kainate group. Malondialdehyde and nitrite and nitrate levels significantly increased in the kainate group (p?<?0.01 and p?<?0.05, respectively), and curcumin significantly lowered these parameters (p?<?0.05). Superoxide dismutase activity significantly decreased in the kainate group (p?<?0.05) and curcumin did not improve it. Rats in the kainate group showed a significant reduction of neurons in Cornu Ammonis 1 (CA1) (p?<?0.05), CA3 (p?<?0.005) and hilar (p?<?0.01) regions, and curcumin significantly prevented these changes (p?<?0.05–0.005). The Timm index significantly increased in the kainate group (p?<?0.005), and curcumin significantly lowered this index (p?<?0.01).

Discussion and conclusion: Curcumin pretreatment can attenuate seizures, lower some oxidative stress markers, and prevent hippocampal neuronal loss and MFS in the kainate-induced model of TLE.     

中西医结合治疗对高血压合并冠心病患者血清胆红素、丙二醛和尿酸水平的影响

目的 探讨中西医结合治疗对高血压合并冠心病患者血清胆红素(Bil)、丙二醛(MDA)和尿酸(UA)水平的影响.方法 将2011年5月至2015年5月入住本院的79例高血压合并冠心病患者按照治疗方法分为对照组(n=39)与观察组(n=40).两组均给予吲达帕胺、氨氯地平为基础的联合降压治疗方案,在此基础上治疗组联合降压宝系列中药治疗,对照组联合降压宝系列中药模拟剂治疗,均0.31g/片,每次2片,每日2次口服,治疗时间为8周.比较两组治疗前后血压及血脂水平、治疗前后血清Bil、UA及MDA水平、治疗前后生活质量评分.结果 两组治疗后血压水平(SBP、DBP)均显著低于治疗前(P＜0.05);观察组治疗后TC、TG及LDL-C水平均显著低于治疗前(P＜0.05),且观察组治疗后HDL-C水平显著高于治疗前(P＜0.05);对照组治疗后仅TC水平低于治疗前(P＜0.05),对照组治疗前后其余血脂指标水平差异均无统计学意义(P＞0.05);两组治疗后血清Bil水平均显著高于治疗前(P＜0.05),且治疗后观察组血清Bil水平显著高于对照组(P＜0.05);两组治疗后血清UA及MDA水平均显著低于治疗前(P＜0.05),且治疗后观察组血清UA及MDA水平均显著低于对照组(P＜0.05);两组治疗后SF-36生活量表各维度(躯体功能、心理功能、社会功能及物质功能)评分均显著高于治疗前(P＜0.05),且治疗后观察组上述各维度评分均显著高于对照组(P＜0.05).结论 中西医结合治疗能够有效改善血压及血脂水平,其作用机制可能是通过降低血清UA及MDA水平、提高Bil水平而发挥作用.