Oxidative stress and free radicals related diseases of the newborn

Free radicals (FRs) generation is an unavoidable consequence of the life in an oxygen-rich atmosphere. FRs can be considered a double-edged sword. Beneficial effects of FRs occur at moderate concentrations and involve physiological roles in cellular responses to noxia, as in defense against infectious agents, in the function of a number of cellular signaling pathways and the induction of a mitogenic response. The over-production of FRs and the insufficiency of an antioxidant mechanism result in oxidative stress (OS), a deleterious process and important mediator of damage to cell structures and tissues. It occurs at birth in all newborns as a consequence of the hyperoxic challenge after the transition from the hypoxic intrauterine environment to extrauterine life. During the perinatal period, OS can be magnified by others predisposing conditions such as hyperoxia, hypoxia, ischemia, hypoxia-reperfusion, inflammation and high levels of non-protein bound iron. Epidemiological studies linked OS occurring during fetal stages and early infancy with adverse health outcomes later in life, indicating that OS is an early event in the etiology of these chronic diseases. Newborns, especially if preterm, are particularly susceptible to OS and damage due to the increased generation of FRs, the lack of adequate antioxidant protection, and the inability to induce antioxidant defenses during the hyperoxic challenge at birth. This impairment of the oxidative balance has been thought to be the common factor of pathologies grouped together as “free radical disease in the neonate” that include retinopathy of prematurity (which may lead to blindness in severe cases), bronchopulmonary dysplasia (a particularly debilitating pulmonary lesion of the preterm infant), periventricular leukomalacia (an important cause of severe neurodisability) and necrotizing enterocolitis. In this review we discuss in detail these perinatal diseases. Particularly, we analyze the current knowledge about the role of OS in their pathogenesis.

The damage effects of oxy free radicals and fulvic acid on chondrocytes

The damage effects of oxy free radical and fulvic acid on cultivated chicken embryo chondrocytes were studied. The results show that the growrth of chondrocytes is inhibited and the morphology of the cells altered. The collagen synthesizing capability of the damaged cell changes somewhat. A noteworthy change of the type of collagen synthesized by the abnormal cells was observed by CMC-chromatography and amino acid analysis. The results indicated that the abnonml cells tend to synthesize type I instead of type II collagen, which is synthesized and secreted by the intact chondrocyte.

The oxidation damage of type II collagen by oxy free radicals and fulvic acid

The features of oxidative damage to type II collagen from pig cartilage, induced by · OH, O2- and fulvic acid from epidemic district of KBD, were studied in vitro. The results from amino acid analysis of the damaged collagen are characterized by a decrease in hydroxyproline and proline contents, and an increase in glutamic acid content. The change arc dependent on·OH and FA concentration. It is postulated that the FA or other toxic xenobiotics induce the generation of free radicals, which play the role of the trigger in KBD development.

Effects of free radicals and amyloid β protein on the currents of expressed rat receptors in Xenopus oocytes

Objective To investigate the effects of free radicals (FRs) and amyloid β protein 1 40 (Aβ 1 40 ) on the functions of expressed neurotransmitter receptors (NRs) in Xenopus oocytes Methods Total RNA and messenger RNA (mRNA) was prepared from 3 month old Wistar rat brain tissues with Promega kits and microinjected into maturated Xenopus oocytes (stages Ⅴ Ⅵ) with 50?nl (50?ng) for each oocyte The microinjected oocytes were incubated with modified Bath's solution at 19 0℃±1 0℃ for receptor expression and their currents were recorded with double electrode voltage clamp technique Superoxide anion free radicals (SAFRs) were produced via a reaction system (HPX/XO) with hypoxanthine (HPX, 0 05?mol/L) and xanthine oxidase (XO, 0 1?U/L) In order to observe the effects of Aβ and SAFRs on the expressed glutamate receptor, HPX/XO and Aβ 1 40 were added to incubation solution at 12?h, 24?h and 96?h before recording Results The results showed that the oocytes expressed functional NRs originating from rat brain tissues These NRs included muscarinic acetylcholine (mACh), glutamate (Glu), dopamine (DA), serotonin (5 HT) and γ aminobutyric acid (GABA) The current characteristics of expressed receptors were inward currents carried by chloride ion with their equibrilium potentials close to -22?mV The extent of effect on the current of expressed glutamate receptor from rat brain was different among different Aβ concentrations and incubation times Aβ 1 40 at a concentration of 20?nmol/L had little effect on the currents of expressed rat brain glutamate receptors up to 24?h of incubation period; but the currents of glutamate receptor were significantly decreased (25% off, P <0 01) in the treatment of 60?nmol/L Aβ 1 40 over 24?h Moreover, when 20?nmol/L Aβ 1 40 was co incubated over 12?h with SAFRs produced by the reaction system of HPX/XO, it was found that the currents of expressed rat brain glutamate receptors had been changed markedly When the oocytes were co treated with 60?nmol/L Aβ 1 40 and SAFRs over a period of 12?h, the currents of glutamate receptor significantly decreased (21% off, P <0 05), and the decreased percentage reached 52% over 24?h co treatment with 60?nmol/L Aβ 1 40 and SAFRs In addition, vitamin E had a partial effect against this inhibitory effect Conclusion The results suggest that Aβ has a kind of inhibitory effect upon the current of the glutamate receptor, similar to the effects of free radicals The effects can be antagonized by vitamin E These imply that Aβ may play a role via inhibiting receptor function in the pathophysiology of Alzheimer's disease

Predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa squamous cell lung cancer:A retrospective analysis

BACKGROUND Lung cancer(LC)is a global medical,social and economic problem and is one of the most common cancers and the leading cause of mortality from malignant neoplasms.LC is characterized by an aggressive course,and in the presence of disease recurrence risk factors,patients,even at an early stage,may be indicated for adjuvant therapy to improve survival.However,combined treatment does not always guarantee a favorable prognosis.In this regard,establishing predictors of LC recurrence is highly important both for determining the optimal treatment plan for the patients and for evaluating its effectiveness.AIM To establish predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa lung squamous cell carcinoma(LSCC).METHODS A retrospective case-control cohort study included 69 patients with LSCC who underwent radical surgery at the Orenburg Regional Clinical Oncology Center from 2009 to 2018.Postoperatively,all patients received adjuvant chemotherapy.Histological samples of the resected lung were stained with Mayer's hematoxylin and eosin and examined under a light microscope.Univariate and multivariate analyses were used to identify predictors associated with the risk of disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with a high risk of disease recurrence and those with a low risk of disease recurrence.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.Differences were considered to be significant at P<0.05.RESULTS The following predictors of a high risk of disease recurrence in patients with stage IIb-IIa LSCC were established:a low degree of tumor differentiation[odds ratio(OR)=7.94,95%CI=1.08-135.81,P=0.049];metastases in regional lymph nodes(OR=5.67,95%CI=1.09-36.54,P=0.048);the presence of loose,fine-fiber connective tissue in the tumor stroma(OR=21.70,95%CI=4.27-110.38,P=0.0002);and fragmentation of the tumor solid component(OR=2.53,95%CI=1.01-12.23,P=0.049).The area under the curve of the predictive model was 0.846(95%CI=0.73-0.96,P<0.0001).The sensitivity,accuracy and specificity of the method were 91.8%,86.9%and 75.0%,respectively.In the group of patients with a low risk of LSCC recurrence,the 1-,2-and 5-year disease-free survival(DFS)rates were 84.2%,84.2%and 75.8%,respectively,while in the group with a high risk of LSCC recurrence the DFS rates were 71.7%,40.1%and 8.2%,respectively(P<0.00001).Accordingly,in the first group of patients,the 1-,2-and 5-year overall survival(OS)rates were 94.7%,82.5%and 82.5%,respectively,while in the second group of patients,the OS rates were 89.8%,80.1%and 10.3%,respectively(P<0.00001).CONCLUSION The developed method allows us to identify a group of patients at high risk of disease recurrence and to adjust to ongoing treatment.

Acute lung injury and acute respiratory distress syndrome： experimental and clinical investigations

Acute lung injury （ALl） or acute respiratory distress syndrome （ARDS） can be associated with various disorders. Recent investigation has involved clinical studies in collaboration with clinical investigators and pathologists on the pathogenetic mechanisms of ALl or ARDS caused by various disorders. This literature review includes a brief historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the long-term experimental studies and clinical investigations from our laboratory, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.

Is there an optimal time to initiate adjuvant chemotherapy to predict benefit of survival in non-small cell lung cancer?

Objective: Adjuvant chemotherapy (AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer (NSCLC); however, few studies have reported the correlation between the time to initiation of AC (TTAC) and survival in NSCLC patients. Methods: The clinical data of 925 NSCLC patients who received curative resection and post-operative AC at the Cancer Hospital of Chinese Academy of Medical Sciences between 2003 and 2013 were retrospectively analyzed. TTAC was measured from the date of surgery to the initiation of AC. Disease-free survival (DFS) was defined as the duration from surgery to the time of tumor recurrence or last follow-up evaluation. The optimal cut-off value of TTAC was determined by maximally selected log-rank statistics. The DFS curve was estimated using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to identify risk factors independently associated with DFS. Propensity score matching (PSM) was performed for survival analysis using the match data. Results: The optimal discriminating cut-off value of TTAC was set at d 35 after curative resection based on which the patients were assigned into two groups: group A (<= 35 d) and group B (> 35 d). There was no significant difference in the DFS between the two groups (P=0.246), indicating that the TTAC is not an independent prognostic factor for DFS. A further comparison continued to show no significant difference in the DFS among 258 PSM pairs (P=0.283). Conclusions: There was no significant correlation between the TTAC and DFS in NSCLC patients. Studies with larger samples are needed to further verify this conclusion.

Humic acid and free radical in environment of Kaschin-Beck disease areas

The humic acid contents in drinking water and soil in Kaschin-Beck disease areas were found more than that of non-disease areas in this research. Changes of free radical concentration in drinking water were agreed with that of humic acid contents in drinking water of Kaschin-Beck disease areas. A positive correlation of free radical concentration and humic acid content in drinking water has been shown (r=0.913) . The structure of I. R. spectra of humic acid under ultraviolet light has been changed. Thus it indicated that free radical was resulted from benzoqiunonyl groups of humic acid in environment.

中医药干预早期非小细胞肺癌的临床效果研究

目的:分析早期非小细胞肺癌(NSCLC)患者根治术后无瘤生存期的影响因素,观察中医药干预对于早期NSCLC患者的影响。方法:采用单臂、单中心数据回顾性研究,分析415例接受中医药干预的早期NSCLC患者的临床资料,运用Kaplan-Meier法对可能影响早期NSCLC预后的因素进行单因素分析,并将经显著性检验后有意义的可疑影响因素纳入Cox回归分析,建立Cox风险比例模型。结果:415例早期NSCLC患者的1年、2年、3年、5年、10年无瘤生存率为96.1%、87.5%、84.0%、76.5%、67.4%。2)单因素分析显示,性别、年龄、吸烟史、手术方式、病理类型、临床分期、中医辨证分型、中医药物及非药物治疗疗程、中医干预空白期、中医综合治疗持续时间为预后相关影响因素(P<0.05)。Cox回归分析显示,性别、临床分期、中医辨证分型、中成药疗程、中医综合治疗持续时间是影响患者预后的独立危险因素。结论:中医药干预可以提高早期NSCLC患者的无瘤生存率,改善预后。2)早期NSCLC患者中,女性、年轻、不吸烟、行电视胸腔镜辅助手术、肺腺癌(贴壁型为主)、临床分期早、气阴两虚及肺脾气虚型患者预后佳。术后中医药干预空白期短且长期中医综合辨证治疗可以提高患者无病生存率。

对神经元氧化应激损伤具有保护活性的灵芝化合物体外筛选及作用机理

【目的】筛选灵芝中具有保护神经元活性的化合物,并探究其相应的作用机理,为研发具有预防和治疗阿尔茨海默病(AD)功效的灵芝功能性食品、保健品和药品提供科学依据。【方法】基于β-淀粉样蛋白(Aβ)诱导的氧化损伤建立细胞模型,对1,1-二苯基-2-三硝基苯肼(DPPH)自由基清除法、铁离子还原/抗氧化能力检测法和2,2-联氮-双(3-乙基苯并噻唑啉-6-磺酸)二铵盐(ABTS)自由基清除法初步评估得到的抗氧化活性较强的灵芝醇提物进行筛选,并对其神经元保护活性进行评价。进一步利用灵芝醇提物中与抗氧化有关的4种三萜类化合物,验证其活性并通过表面等离子共振技术探究其相关作用机理。【结果】DPPH、ABTS自由基清除及铁离子还原/抗氧化能力等体外理化初筛与细胞水平筛选试验结果表明,6种灵芝醇提物(108、161、106-2、171、173和109)抗氧化保护神经元活性较强,其中108、109和106-2样品对大鼠肾上腺髓质嗜铬瘤细胞(PC12细胞)氧化应激损伤的保护效果最好;灵芝醇提物可通过缓解细胞周期紊乱、抑制细胞早期凋亡、提高超氧化物歧化酶(SOD)活性和谷胱甘肽(GSH)含量,抑制丙二醛(MDA)含量上升来发挥神经元保护作用。灵芝醇提物108、106-2和109中4种三萜类化合物(灵芝醛A、灵芝酸B、灵芝酸C2和灵芝酸LM2)的平均含量占比相对较高。活性验证表明4种化合物对细胞氧化应激损伤均有明显修复效果,其中灵芝醛A与Aβ_(1~42)具有较强的亲和力,其KD值为15.62μmol/L,可通过与Aβ_(1~42)竞争性结合来抑制Aβ_(1~42)与RAGE结合。【结论】灵芝醇提物的抗氧化神经元活性通过灵芝酸C2、灵芝酸B、灵芝酸LM2和灵芝醛A 4种化合物的协同效应来实现。灵芝醛A能通过与RAGE竞争性结合来减轻或抑制Aβ_(1~42)细胞毒性作用。灵芝具有开发防治AD功能性产品的潜力。

参芪固金汤辅助治疗放射性肺炎疗效及对IL-8、氧自由基的影响

目的研究参芪固金汤辅助治疗放射性肺炎(Radiation pneumonia, RP)的疗效及对患者白细胞介素-8(Interleukin 8,IL-8)、氧自由基的变化影响。方法选取医院2020年4月—2022年12月收治的RP患者80例。根据随机数字法分为常规组(40例)和参芪固金汤组(40例)。常规组给予激素、抗感染、止咳化痰、营养支持等常规治疗,参芪固金汤组在常规组基础上加用参芪固金汤治疗。比较两组肺功能、氧自由基、炎症因子的水平,统计两组疗效。结果参芪固金汤组总有效率[90.00%(36/40)]高于常规组[72.50%(29/40)],差异有统计学意义(P<0.05)。两组治疗前肺功能指标组间比较,差异无统计学意义(P>0.05)。参芪固金汤组治疗后肺活量(Vital capacity, VC)[(2.92±0.45)L]、一氧化碳弥散量(Carbon monoxide diffusing capacity, DLCO)[(18.24±3.96)mL/min]水平高于常规组(P<0.05)。两组治疗前白细胞介素-1(Interleukin-1,IL-1)、IL-8、降钙素原(Calcitonin, PCT)、转化生长因子-β1(Transforming growth factor-β1,TGF-β1)、氧自由基水平组间比较,差异无统计学意义(P>0.05)。参芪固金汤组治疗后IL-1、IL-8、PCT、TGF-β1水平低于常规组,其他指标高于常规组(P<0.05)。结论参芪固金汤辅助治疗RP可减轻炎症反应,清除氧自由基,改善肺功能。

扶正祛邪方对ⅠA期微乳头/实性成分阳性浸润性肺腺癌术后患者免疫功能及无病生存期的影响

目的观察扶正祛邪方对ⅠA期微乳头/实性成分阳性(MP/SD+)浸润性肺腺癌术后患者免疫功能及无病生存期(DFS)的影响,为ⅠA期肺腺癌患者的术后治疗提供参考。方法将216例ⅠA期MP/SD+浸润性肺腺癌术后患者分为治疗组(108例)、对照组(108例),对照组不予抗肿瘤干预,治疗组予扶正祛邪方口服,定期随访。观察两组外周血免疫指标[CD3^(+)、CD4^(+)、CD8^(+)、自然杀伤(NK)细胞表达水平及CD4^(+)/CD8^(+)比值]的变化情况,记录DFS,计算无病生存率,绘制Kaplan-Meier生存曲线,并进行安全性评价。结果①最终纳入统计者213例,其中治疗组105例、对照组108例。②治疗前后组内比较,治疗组CD3^(+)、NK细胞比例上升(P<0.05),CD8^(+)比例下降(P<0.05);对照组免疫指标变化差异无统计学意义(P>0.05)。组间治疗后比较,治疗组CD3^(+)、NK细胞比例及CD4^(+)/CD8^(+)比值高于对照组(P<0.05),CD8^(+)比例低于对照组(P<0.05)。③治疗组105例患者中,5例患者复发,1年、2年和3年无病生存率分别为98.9%、96.5%和92.0%;对照组108例患者中,11例复发,1年、2年和3年无病生存率分别为94.9%、89.8%和81.9%。绘制Kaplan-Meier生存曲线后,两组差异有统计学意义(P<0.05)。④试验期间,两组患者血常规、肝肾功能等安全性指标未见明显变化。结论扶正祛邪方可有效调节ⅠA期MP/SD+浸润性肺腺癌术后患者的免疫功能,进而延长DFS,改善预后。

基于动脉期增强CT影像组学模型预测小细胞肺癌无进展生存期

目的 观察基于动脉期增强CT影像组学模型预测小细胞肺癌(SCLC)患者无进展生存期(PFS)的价值。方法 回顾性纳入210例SCLC患者,按7∶3比例将其随机分为训练集(n=147)与测试集(n=63),以Cox比例风险回归分析获取PFS率的临床独立影响因素并构建临床模型;提取肿瘤影像组学特征,于训练集遴选与PFS率最为相关者构建影像组学模型,计算影像组学评分(Radscore)并据以对疾病进展风险进行分层,比较不同层次PFS率;联合临床独立影响因素及影像组学特征构建临床-影像组学模型。于测试集评估并比较各模型预测SCLC患者PFS率的区分度、校准度及临床净收益。结果 广泛期为SCLC患者PFS缩短的临床独立危险因素[HR=1.841,95%CI(1.288,2.633),P=0.001]。基于训练集选出5个与PFS率最为相关的影像组学特征,根据Radscore区分疾病进展风险低(Radscore<0.235)或高(Radscore≥0.235),后者PFS率低于前者(P<0.001)。临床模型、影像组学模型及临床-影像组学模型预测测试集6个月内PFS率的受试者工作特征曲线下面积(AUC)分别为0.646、0.920及0.931,预测12个月内PFS率分别为0.591、0.917及0.919;临床模型的一致性指数(C-index)为0.595,影像组学模型及临床-影像组学模型的C-index分别为0.878和0.884,均高于临床模型。相比临床模型,影像组学模型净重新分类指数(NRI)为75.82%(P<0.001)、综合判别改善指数(IDI)为59.76%(P<0.001),临床-影像组学模型依次为78.94%(P<0.001)及61.13%(P<0.001),后二模型间差异均无统计学意义(P均>0.05)。DCA结果显示影像组学模型和临床-影像组学模型的临床净收益均高于临床模型。结论 基于动脉期增强CT影像组学模型可预测SCLC患者PFS率,有助于临床制定个体化治疗方案。

IB期肺腺癌患者辅助治疗方案的筛选

目的探索IB期肺腺癌患者的辅助治疗方案。方法收集2013年1月~2021年12月在我院行手术治疗的IB期肺腺癌患者,根据术后不同辅助治疗模式分为辅助靶向治疗组(EGFR-TKIs)、辅助化疗组(CT)和临床观察组(CO)。对比3组患者的临床资料和随访结果,无疾病生存期、总生存的分析采用Kaplan-Meier法并行log-rank检验,COX回归分析患者无疾病生存期(DFS)的预测因素。主要研究终点是5年DFS率,次要研究终点为DFS、3年总生存期(OS)以及辅助治疗的安全性。结果共纳入653例术后诊断为IB期肺腺癌患者,其中EGFR-TKIs组111例,CT组108例,CO组434例。中位随访时间43个月,TKIs组、CT组和CO组的5年DFS率分别为92.8%、80.7%及81.7%,TKIs组的5年DFS率显著高于CO组(P<0.01)。TKIs组、CT组和CO组的3年OS均无统计学差异。亚组分析显示,T3~4 cmN0M0中TKIs组、CT组和CO组的5年DFS率分别为92.6%、84.0%及81.4%,TKIs组的5年DFS率显著高于CO组(P<0.05),3组间的3年OS无统计学差异。而T2ViscPlN0M0中TKIs组、CT组和CO组的5年DFS率分别为95.1%、71.4%及83.5%,组间差异并无统计学意义,3组间的3年OS亦无统计学差异。多因素COX回归分析结果显示,年龄(P<0.05;HR 0.631,95%CI 0.401-0.993)、实性结节(P<0.01;HR 7.620,95%CI 3.037-19.121)、微乳头/实性成分(P<0.05;HR 1.776,95%CI 1.010-3.122)、脉管癌栓(P<0.05;HR 2.981,95%CI 1.198-7.419)及辅助治疗(P<0.01)是DFS的独立预测因素。安全性方面,皮疹、甲沟炎及腹泻仍然是靶向药物最常见的不良反应。化疗组不良反应主要为血液系统的抑制和胃肠道反应,3级以上不良反应率高于TKIs组(44.4%vs 9.0%)。结论辅助靶向治疗有助于提高T3~4 cmN0M0的IB期肺腺癌患者的DFS,但T2ViscPlN0M0患者并不能从靶向治疗中获益。辅助化疗并不能改善IB期肺腺癌患者的DFS和OS。

自由基与疾病研究进展

随着基础医学和生命科学的不断发展,人们对自由基的研究越来越多,其中就有大量关于自由基与疾病的研究。自由基作为机体的正常代谢产物,在平衡状态下,其在抗菌、消炎和抑制肿瘤等方面具有重要作用和意义;一旦平衡被打破,如机体受到疾病或某些外源性药物和毒物的侵害,自由基便会产生强大的伤害作用,造成生物膜的脂质过氧化损伤,引起酶、氨基酸、蛋白质的氧化破坏,对内脏器官、免疫系统的形态功能产生影响,从而引起机体疾病,甚至死亡。目前,研究发现很多疾病的发生发展都与自由基有关。文章就自由基的产生、种类、与疾病的关系及清除进行了综述。

油酸引起肺水肿的机制探讨

作者从三个不同层次(整体肺、离体肺及肺血管内皮细胞)的肺损伤模型证实了油酸引起的急性肺水肿中有氧自由基参与,来自嘌呤氧化酶的氧自由基起着原发始动作用,而来自嗜中性白细胞的氧自由基起着继发和扩大损伤的作用。

药物保护体外冲击波碎石肾损伤的作用及其机制

目的 了解钙离子拮抗剂和自由基清除剂对体外冲击波 (ESW )肾损伤的保护作用及其作用机制。方法 制备成单肾模型的雌性SD大鼠 12 0只 ,随机均分为 6组 ,在单用和联用钙离子拮抗剂Verapamil和不同剂量自由基清除剂超氧化物歧化酶 (SOD)后 ,以JDPN V型碎石机 14kV对肾脏震波冲击 10 0 0次 ,观察大鼠尿N 乙酸 β 葡萄糖苷酶 (NAG)、尿内皮素 (ET)、尿丙二醛 (MDA)水平和内生肌酐清除率 (CCr)的变化以及肾脏组织学和超微结构改变。结果 所有治疗组尿NAG、尿MDA的升高幅度和CCr降低幅度均明显小于对照组 ,组织损伤程度也比较轻 ,恢复较快。SOD用 2万和 4万U/kg体重时生化指标和病理改变无显著差别。Verapamil组尿ET升高幅度下降 ;联用组效果最好。结论 钙离子拮抗剂不仅有减轻脂质过氧化的作用 ,还可以减少ET的释放 ,对ESWL肾损伤有显著的保护作用 。

葛根素对糖尿病致肺损伤的保护作用及其机制的研究

目的:探讨糖尿病对肺脏损伤及葛根素对肺组织影响的可能机制。方法:腹腔注射链脲佐菌素(STZ)建立大鼠糖尿病(DM)模型,SD大鼠随机分为对照组(C组)、糖尿病组(DM组)、糖尿病+葛根素组(DM+Pur组)。检测注药前及模型成立后第20d、40d、60d的血糖及体重的改变。检测肺组织中一氧化氮(NO)和丙二醛(MDA)的含量、超氧化物歧化酶(SOD)活性。结合光镜、电镜、免疫组织化学染色方法综合评价。结果:①DM组NO、MDA高于C组(P<0.01),SOD活性低于C组(P<0.01),DM+Pur组NO含量明显低于DM组(P<0.01),MDA含量40d开始显著降低(P<0.01),SOD活性高于DM组(P<0.01)。②光镜下见肺泡隔增厚,炎性细胞浸润;电镜下见Ⅱ型肺泡上皮细胞微绒毛数量明显减少,嗜锇性板层小体数量明显减少,细胞间质胶原纤维增生,葛根素可减轻肺组织上述病理性改变。③免疫组织化学染色结果:DM组细胞胞质中可见ONOO-特征性代表物硝基酪氨酸(ni-trotyrosine,NT)黄染阳性信号表达,且较对照组略为增强,DM+Pur组黄染信号较DM组略为减弱。结论:①DM时可发生肺组织损伤,可能与长期高血糖诱导产生大量自由基有关。②NO/ONOO-通路是DM造成肺组织细胞损伤的机制之一。③初步证实葛根素能在一定程度上抑制高血糖诱导肺组织中自由基的过量生成,降低肺组织中的ONOO-的过度表达,这可能是其抗DM时肺组织损伤的作用机制之一。

肉苁蓉总苷对β-淀粉样肽所致阿尔采末病小鼠模型学习记忆的影响及其机制

目的研究肉苁蓉总苷(G lycosides of c istanche,GCs)对β-淀粉样肽(β-AP)所致阿尔采末病(AD)模型小鼠的保护作用,并探讨其作用机制。方法采用小鼠脑室内一次性微量注射β-AP25-35诱发β-AP在脑内的沉积,造成AD小鼠模型。10 d后,一次性训练被动回避跳台实验测定AD小鼠学习记忆能力;检测脑组织SOD活性、MDA含量及GSH-Px活性;电子显微镜检测脑组织神经细胞的病理变化;TUNEL法检测脑细胞凋亡;免疫组化SABC法检测Bax/Bc l-2的表达。结果GCs可提高β-AP所致AD小鼠学习记忆水平;降低脑组织MDA含量,提高SOD及GSH-Px活性;使脑组织中某些病理改变得到改善;降低脑细胞凋亡率;使Bax的表达减弱,Bc l-2的表达增强。结论GCs对β-淀粉样肽所致AD小鼠学习记忆能力提高,其作用机制可能与其增强自由基清除酶活性,防止脂质过氧化作用,抑制β-AP在脑内的沉积及抑制脑细胞凋亡有关。

牛磺酸在大鼠止血带休克后肺损伤中的保护作用

目的 :观察牛磺酸对大鼠止血带休克 (ToS)后肺损伤的保护作用 .方法 :采用大鼠止血带休克模型 ,将Wistar大鼠随机分为 3组 :对照组 (control)、止血带休克组 (ToS)、牛磺酸 +止血带休克组 (Tau +ToS) ,分别测定动脉血氧分压 (PaO2 )和二氧化碳分压 (PaCO2 ) ,肺系数 (LI)和肺通透指数 (LPI)以及肺组织黄嘌呤氧化酶 (XOD)、超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH PX)、过氧化氢酶 (CAT)及活性氧 (ROS)、组织Ca2 + 含量、丙二醛 (MDA)和髓过氧化物酶 (MPO)的含量 .结果 :po牛磺酸可有效地改善肺呼吸功能 [PaO2 (1 1 .7± 1 .6 )kPavs (8.5± 0 .7)kPa ,P <0 .0 1 ],降低自由基生成酶的活性[XOD (6 7± 7) μkat/gvs (79± 1 3) μkat/g;(76± 1 1 ) μkat/gvs(1 0 9± 2 6 ) μkat/g ,P <0 .0 5或 P <0 .0 1 ],增加自由基清除酶的活性 [SOD (4 8± 8) μkat/gvs (2 0± 3) μkat/g;CAT (38± 8)vs (1 9± 6 ) μkat/g ;GSH PX (86± 2 ) μkat/gvs (2 3± 4 ) μkat/g,P <0 .0 1 ],抑制组织脂质过氧化的发生 [MDA (1 0 8± 1 7)μmol/gvs (1 4 7± 2 3) μmol/g ,P <0 .0 5 ;(1 32± 1 3) μmol/gvs(1 5 1± 1 9) μmol/g ,P <0 .0 5 ],减轻组织水肿及中性粒细胞的聚集 [MPO (0 .0 1 7± 0 .0