冠心病介入术后氧自由基的生成及其对脂质过氧化和纤溶的影响

目的:探讨冠心病介入治疗术后氧自由基的生成及其对患者体内脂质过氧化和纤溶状况的影响。方法:48例接受经皮冠脉介入治疗(PCI)术的冠心病患者分别于术前,术后即刻、30 min、1 h、24 h和一周采用ELISA法测定血浆中丙二醛、D-二聚体、血管假性血友病因子相关抗原(vWF Ag)浓度。结果:PCI术后短时间内(0～24 h)血浆中丙二醛、D-二聚体,vWFAg水平均明显升高(P<0．05)。结论:PCI术后短时间内即有大量的氧自由基生成,凝血系统的激活和继发性纤溶功能亢进。     

The Oxidant-Antioxidant Balance in Mild Asthmatic Patients

We investigated the oxidant-antioxidant balance and the effect of inhaled corticosteroids on this balance in mild stable asthmatics. Included in the study were 30 mild asthmatic patients (11 male, 19 female, mean age (year) ± SD: 35.1 ± 9.7) and 26 healthy adults (7 male, 19 female, mean age (year) ± SD: 40.8 ± 13.3). In all study groups, the peripheral venous blood samples were taken for plasma malonyldialdehyde (MDA), a parameter of lipid peroxidation caused by the oxidants, and erythrocyte superoxide dismutase (SOD), an antioxidant enzyme. The mean plasma MDA level was lower in the asthmatic group (5.7 ± 1.2 nmol/ml) than in the healthy group (6.3 ± 1.7 nmol/ml); and the mean erythrocyte SOD level was higher in asthmatic group (1086.4 ± 247.4 U/gHb) than in the healthy group (1028.0 ± 230.0 U/gHb). However, there were no significant differences in measurements of both plasma MDA levels and erythrocyte SOD enzyme activities between the groups (respectively, p = 0.1 and p = 0.4). When asthmatic patients were divided into subgroups as inhaled steroid user and no inhaled steroid user, no significant differences were observed in the measurements of either plasma MDA level or erythrocyte SOD enzyme activity between the mentioned subgroups. According to the results of our study, we can say that oxidant-antioxidant balance is not significantly affected in mild asthmatics or measurement of plasma level of MDA and erythrocyte SOD enzyme activity is not sensitive to the oxidant-antioxidant balance in mild asthmatics.     

肝细胞色素p450 1A1在大鼠非酒精性脂肪肝形成中的作用

目的研究肝细胞色素p450 1A1在非酒精性脂肪肝大鼠形成中的作用.方法Wistar大鼠40只,随机分为正常对照组和高脂饲料2、4、8和12周组(其中每组各8只);HE染色光镜观察肝脏组织病理改变;硫代巴比妥酸法测定肝脏组织丙二醛(MDA)的含量变化;免疫组织化学和Western blot方法研究高脂饲料诱导的大鼠脂肪肝形成中肝细胞色素p450 1A1表达变化.结果高脂饲料组大鼠肝脏内MDA含量明显高于对照组,随着脂肪肝程度的加重,MDA含量逐渐增强,肝细胞色素p450 1A1蛋白表达亦明显增强.结论非酒精性脂肪肝大鼠肝细胞色素p450 1A1表达变化与脂肪肝引起的脂质过氧化损伤程度密切相关.     

降压灵对自发性高血压大鼠血清中MDA、SOD、NO的影响

目的本试验通过观察降压灵对自发性高血压大鼠血清中的丙二醛（MDA）、超氧化物歧化酶（SOD）、一氧化氮（NO）的影响,进而探讨降压灵的降压机理。方法取Wistar组、SHR组、复方罗布麻组、降压灵小剂量组、中剂量组、大剂量组大鼠血清,用752分光光度计测定血清中的NO、MDA含量以及SOD活性。结果降压灵可以显著的提高血清中SOD活性和NO含量,降低血清中MDA含量。结论降压灵有扩张血管、清除超氧自由基和抗氧化作用。     

依达拉奉对实验性蛛网膜下隙出血后脑损伤的保护作用

目的观察依达拉奉对蛛网膜下隙出血后脑组织丙二醛（MDA）含量及诱导型一氧化氮合酶（iNOS）表达的影响。方法采用血管内穿刺法建立蛛网膜下隙出血（SAH）模型,将24只雄性成年大鼠随机分为假手术组、SAH组、SAH＋依达拉奉组（依达拉奉组）,72h后处死大鼠。处死前每天统计大鼠神经功能缺损评分;处死后采用硫代巴比妥酸法检测大鼠脑组织中MDA含量,运用Westernblot方法检测大鼠脑组织中iNOS蛋白的表达。结果依达拉奉组大鼠神经功能评分高于SAH组,而MDA含量明显低于SAH组（P〈0.05）;Westernblot检测显示,依达拉奉可降低脑组织iNOS的表达。结论依达拉奉可改善蛛网膜下隙出血后脑损伤,具有一定的神经保护作用。     

水芹乙酸乙酯提取物对大鼠心肌缺血和缺血再灌注损伤的保护作用研究

目的:研究水芹乙酸乙酯提取物对大鼠心肌缺血和缺血再灌注损伤的保护作用。方法:使用线栓法复制急性心肌缺血和缺血再灌注损伤模型。缺血前5min静脉注射水芹乙酸乙酯提取物,动态观察模型大鼠心电图的变化,测定心肌缺血引起的心律失常和心肌梗死面积、心肌缺血再灌注引起心律失常情况、血浆中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果:水芹乙酸乙酯提取物可显著对抗心肌缺血引起的心律失常和缩小心肌梗死面积;可显著对抗心肌缺血再灌注损伤引起的心律失常,提高血浆中SOD活性和降低MDA含量。结论:水芹乙酸乙酯提取物对大鼠心肌缺血和缺血再灌注损伤具有保护作用,其机制可能与抗过氧化作用有关。     

七叶皂苷钠对油酸制备大鼠急性肺损伤模型的干预研究

目的探讨七叶皂苷钠对油酸诱导大鼠急性肺损伤模型的干预作用。方法♂SD大鼠54只随机分为5组,分别为正常对照组、注射七叶(非油酸造模)组、油酸造模组、甲基强的松龙组和七叶皂苷钠组。采用鼠尾静脉缓慢注射油酸(OA,0.1ml.kg-1)复制大鼠急性肺损伤模型,模型复制成功后按相应措施处理观察并取血取材检测相关指标。观察检测指标有肺组织形态学、肺湿/干重(W/D)、光镜下半定量肺损伤评分(IQA)、血气分析动脉血氧分压(PaO2)、血浆及肺组织匀浆超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量。结果①肺组织形态学:七叶皂苷钠组及甲基强的松龙组肺表面充血程度较油酸组明显减轻,气管内粉红色分泌物溢出减少;光镜下,七叶皂苷钠组及甲基强的松龙组较油酸造模组肺泡腔内炎症细胞渗出减轻;②肺湿/干重(W/D):油酸造模组W/D较空白对照组明显升高,七叶皂苷钠组及甲基强的松龙组W/D较油酸造模组明显降低;③光镜下半定量肺损伤评分(IQA):油酸造模组IQA较空白对照组明显升高,七叶皂苷钠组及甲基强的松龙组IQA较油酸造模组明显降低;④血气分析动脉血氧分压(PaO2):油酸造模组PaO2较空白对照组明显降低,七叶皂苷钠组及甲基强的松龙组PaO2较油酸造模组升高;⑤血浆及肺组织匀浆超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量:油酸造模组血浆及肺组织SOD活性较空白对照组明显降低,七叶皂苷钠组及甲基强的松龙组血浆和肺组织SOD活性较油酸造模组明显升高;油酸造模组血浆及肺组织MDA含量较空白对照组明显升高,七叶皂苷钠组及甲基强的松龙组血浆和肺组织MDA含量较油酸造模组明显降低。结论七叶皂苷钠通过对急性肺损伤大鼠氧化应急的调节作用,以改善W/D、IQA、PaO2,从而为临床治疗急性肺损伤提供一个可能的途径。     

雷米普利与BQ-123对大鼠在体心肌缺血/再灌注氧化损伤的保护作用

目的研究雷米普利与BQ-123单用及合用对大鼠在体心肌缺血/再灌注损伤的影响,并从氧化-抗氧化角度初步探讨其机制。方法健康♂Wistar大鼠随机分为假手术(Sham)、缺血/再灌注(I/R)、雷米普利(RAM)、BQ-123(BQ)及联合给药(R&B)共5组。除Sham组,其余均行I/R过程。I/R前24h,RAM及R&B组按1mg.kg-1剂量以雷米普利生理盐水溶液灌胃,其余组均以等剂量生理盐水(NS)灌胃;I/R过程中,BQ及R&B组按10μg.kg-1.min-1,于缺血前10min至缺血30min末用注射泵恒速左侧股静脉输入BQ-123生理盐水溶液2ml,其余组均以等剂量NS持续静脉输入。观察动物心率、血压、心电图ST-段变化,记录缺血期室性心律失常(VA);TTC染色检测心肌梗死情况;比色法检测心肌组织中总-超氧化物歧化酶(T-SOD)、锰-超氧化物歧化酶(Mn-SOD)、过氧化氢酶(CAT)活力及丙二醛(MDA)含量。结果与I/R组比较,各给药组ST-段抬高幅度均明显降低、缺血期VA出现时间明显推迟且持续时间明显缩短、心律失常发生率均明显下降、梗死面积明显缩小、心肌组织T-SOD、Mn-SOD及CAT活力均明显升高、MDA含量明显下降。与单用药组比较,联合给药组在VA出现及持续时间、梗死面积、T-SOD和Mn-SOD活力及MDA含量方面变化更为明显。结论雷米普利、BQ-123单用及联合应用均对大鼠在体心肌缺血/再灌注损伤有保护作用,且两药合用在推迟缺血期VA的出现时间,缩短其持续时间,缩小心肌梗死面积,提高心肌组织SOD活力,降低MDA含量方面优于两药各自单用。     

Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-κB, p38 and JNK MAPK pathway

Cardiac dysfunction is a major cause of morbidity and mortality worldwide due to its complex pathogenesis. However, little is known about the mechanism of arsenic-induced cardiac abnormalities and the use of antioxidants as the possible protective agents in this pathophysiology. Conditionally essential amino acid, taurine, accounts for 25% to 50% of the amino acid pool in myocardium and possesses antioxidant properties. The present study has, therefore, been carried out to investigate the underlying mechanism of the beneficial role of taurine in arsenic-induced cardiac oxidative damage and cell death. Arsenic reduced cardiomyocyte viability, increased reactive oxygen species (ROS) production and intracellular calcium overload, and induced apoptotic cell death by mitochondrial dependent caspase-3 activation and poly-ADP ribose polymerase (PARP) cleavage. These changes due to arsenic exposure were found to be associated with increased IKK and NF-κB (p65) phosphorylation. Pre-exposure of myocytes to an IKK inhibitor (PS-1145) prevented As-induced caspase-3 and PARP cleavage. Arsenic also markedly increased the activity of p38 and JNK MAPKs, but not ERK to that extent. Pre-treatment with SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated NF-κB and IKK phosphorylation indicating that p38 and JNK MAPKs are mainly involved in arsenic-induced NF-κB activation. Taurine treatment suppressed these apoptotic actions, suggesting that its protective role in arsenic-induced cardiomyocyte apoptosis is mediated by attenuation of p38 and JNK MAPK signaling pathways. Similarly, arsenic intoxication altered a number of biomarkers related to cardiac oxidative stress and other apoptotic indices in vivo and taurine supplementation could reduce it. Results suggest that taurine prevented arsenic-induced myocardial pathophysiology, attenuated NF-κB activation via IKK, p38 and JNK MAPK signaling pathways and could possibly provide a protection against As-induced cardiovascular burden.     

Gel entrapment culture of rat hepatocytes for investigation of tetracycline-induced toxicity

This paper aimed to explore three-dimensionally cultured hepatocytes for testing drug-induced nonalcoholic steatohepatitis. Gel entrapped rat hepatocytes were applied for investigation of the tetracycline-induced steatohepatitis, while hepatocyte monolayer was set as a control. The toxic responses of hepatocytes were systematically evaluated by measuring cell viability, liver-specific function, lipid accumulation, oxidative stress, adenosine triphosphate content and mitochondrial membrane potential. The results suggested that gel entrapped hepatocytes showed cell death after 96 h of tetracycline treatment at 25 μM which is equivalent to toxic serum concentration in rats, while hepatocyte monolayer showed cell death at a high dose of 200 μM. The concentration-dependent accumulation of lipid as well as mitochondrial damage were regarded as two early events for tetracycline hepatotoxicity in gel entrapment culture due to their detectability ahead of subsequent increase of oxidative stress and a final cell death. Furthermore, the potent protection of fenofibrate and fructose-1,6-diphosphate were evidenced in only gel entrapment culture with higher expressions on the genes related to β-oxidation than hepatocyte monolayer, suggesting the mediation of lipid metabolism and mitochondrial damage in tetracycline toxicity. Overall, gel entrapped hepatocytes in three-dimension reflected more of the tetracycline toxicity in vivo than hepatocyte monolayer and thus was suggested as a more relevant system for evaluating steatogenic drugs.