用怀孕母鼠及其子鼠复制大骨节病实验模型的研究

本文首次报道应用怀孕母鼠进行实验,复制大骨节病模型。同胎母鼠经过交配后分笼饲养;对照组饲实验室常规粮、蒸馏水;非病区组饲辽宁省北镇粮、100ppm 北镇 FA 水;病区组饲甘肃省天水粮、100ppm 天水 FA 水。子鼠生后6周检测,结果是:1、病区组仔鼠生长速度缓慢,体重明显小于非病区组和对照组;2、与非病区组比较,病区组子鼠血液 SOD 活力显著升高,GSH-Rx 活力显著降低,LPO 量也显著减少。心肌、肝、和腓肠肌三种组织相比较,心肌反应性较安定,酶活力改变不大;肝组织反应强烈,SOD 活力显著降低,GSH-Px 活力显著升高,与血液的酶活力变化相反;腓肠肌 SOD 活力没有变化,GSH-Px 活力显著降低,LPO 量也显著减少,改变与血液相似,可能属于病理性反应;3、病区组子鼠的胫骨近端见有骺板变薄、酸性粘多糖明显减少、骨小梁稀少、深层肥大细胞胞质少、核缺失等病理改变。对大骨节病的有机质病因学与过氧化损伤的关系做了粗浅讨论。     

还原型谷胱甘肽对体外循环下心肌缺血再灌注损伤的影响

对15例心脏直视手术患者给予还原型谷胱甘肽(GSH),观察在心肌缺血再灌注过程中血浆过氧化脂质(LPO)、红细胞超氧化物歧化酶(SOD)含量动态变化,并以15例同种病人作为对照,发现对照组于再灌注期血浆LPO显著升高,红细胞SOD显著降低;GSH组血浆LPO显著低于对照组,红细胞SOD显著高于对照组。提示外源性GSH有可能减轻心肌缺血再灌注损伤。     

硝苯地平和维生素C对心肌缺血-再灌注中血浆LFO和红细胞SOD的影响

观察硝苯地平和维生素C对体外循环心脏直视手术病人心肌缺血-再灌注过程中血浆LPO和红细胞SOD含量的影响,并与常规手术病人进行对比,发现在再灌注过程中,对照组血浆LPO含量升高,红细胞SOD含量降低,硝苯地平组和维生素C组上述指标无明显变化。表明硝苯地平具有清除氧自由基和抗脂质过氧化作用,效果与维生素C相同。     

丹参对家兔实验性动脉粥样硬化预防作用的研究

丹参预防组主动脉斑块面积占主动脉总面积的百分比为（１９．８５±１１．７９％），明显小于动脉粥样硬化（ＡＳ）模型组（３７．７９±１０．８０％），Ｐ＜０．０５。丹参有显著保护超氧化物歧化酶（ＳＯＤ）活性和清除脂质过氧化物中间产物丙二醛（ＭＤＡ）的作用。丹参能明显抑制在高脂条件下３Ｈ－ＴｄＲ掺入培养的平滑肌（ＳＭＣ），抑制ＳＭＣ、ＤＮＡ合成。本研究初步探讨了丹参抑制家兔实验性ＡＳ病变发生发展的作用机制。     

月见草油抗衰老作用的实验研究

目的探讨月见草油抗衰老的作用和机制。方法用含月见草油的饵料饲喂大鼠80d后采血,用TBA反应比色法和光化学扩增法测定不同剂量,不同组别的大鼠脂质过氧化物和SOD的活性情况。结果月见草油能显著提高大鼠血清中SOD和Mn-SOD活性,能显著降低大鼠血浆中脂质过氧化物的生成,且呈剂量-效应关系。结论月见草油含有抗氧化物质的成分,对于清除或抑制自由基的产生,阻断自由基反应蔓延,减轻对机体的损伤,延缓衰老,具有十分重要的意义。     

依布硒啉对心肌缺血再灌注损伤大鼠心功能的保护作用及其机制

目的探讨依布硒啉(Ebs)对心肌缺血再灌注损伤大鼠心功能的保护作用及其机制。方法取24只雄性大鼠,结扎其冠状动脉左前降支30 min、灌注90 min制作心肌缺血再灌注损伤模型,观察Ebs对大鼠心功能、心肌酶学和脂质过氧化的影响。结果Ebs能够对抗心肌缺血再灌注引起的左心室内压(LVSP)、左心室内压最大上升与下降速率(±dp/dtmax)、动脉血压下降,并能够稳定心肌组织Na -K -ATPase和Ca2 -Mg2 -AT-Pase活性,降低丙二醛(MDA)含量和增高SOD活性。结论提示依布硒啉(Ebs)对大鼠心肌缺血再灌注引起的心功能减弱具有明显的保护作用,其机制可能为改善能量代谢障碍,抑制自由基生成或清除氧自由基。     

北五味子抗衰老作用的实验研究

北五味子[Schisandra Chinensis(Turcz)Baill]属木兰科植物,药用其成熟、干燥的果实.临床多用于久咳虚喘、津亏口渴、遗精、自汗、久泻、神经衰弱、肝炎等症[1].近年来,通过大量动物和临床实验发现五味子还有多种临床疗效,但是,对于北五味子的抗衰老作用及其机理的研究尚未见报道[1].     

清开灵注射液对大鼠心肌缺血再灌注损伤的保护作用

目的探讨清开灵(QKL)注射液对大鼠实验性缺血/再灌注(I/R)损伤的保护作用及机制。方法 Wistar大鼠40只,随机分为假手术组、模型组、清开灵注射液高剂量组(QKL 40 mg/kg)、清开灵注射液低剂量组(QKL 20 mg/kg),每组10只。结扎大鼠冠状动脉左前降支40 min、再灌120 min制备心肌I/R损伤模型。检测QKL对I/R损伤大鼠血清中LDH、CK、AST、SOD、MDA、NO含量的影响;同时以TTC染色检测心肌梗死面积变化。结果与模型组比较,QKL高剂量组及QKL低剂量组大鼠血清中LDH、CK、AST含量明显降低(P<0.05),SOD活性明显升高(P<0.01),MDA及NO含量降低(P<0.01)。QKL高剂量组及QKL低剂量组心肌梗死面积明显低于模型组(P<0.05)。免疫组化法检测结果显示,QKL高剂量组及QKL低剂量组心肌细胞iNOS表达量低于模型组(P<0.05)。结论 QKL可能通过抑制iNOS,对大鼠心肌I/R损伤具有保护作用。     

急性心肌缺血氧自由基与血液高凝状态的实验研究

本文研究急性心肌缺血氧自由基及其清除剂对抗凝血酶及纤溶系统的影响。结果表明:心肌缺血4小时引起血浆丙二醛(MDA)增高,血浆抗凝血酶Ⅲ(AT-Ⅲ)及组织型纤溶酶原激活剂(t-PA)活性降低。纤溶酶原激活剂抑制物(PAI)活性增高。MDA与AT-Ⅲ呈负相关,与PAI呈正相关。自由基清除剂超氧化物歧化酶(SOD)及过氯化氢酶(CAT)可降低自由基,升高AT-Ⅲ与t-PA活性,降低PAI活性。作者认为氧自由基可能对急性心肌缺血产生高凝状态起重要作用。     

Cigarette Smoking and Free Radical Activity in Young Adults with Insulin-dependent Diabetes

Cigarette smoke is potentially capable of generating a high free radical load in the body and many patients with diabetes are smokers. This study was designed to investigate the relationship between long-term smoking and free radical activity in young adult insulin-dependent diabetic patients with no evidence of macrovascular disease. Eighty-five patients (48 male) aged 17–40 years were studied. Mean duration of diabetes was 10.5 years (0.08–33) and 39 were cigarette smokers. All had normal serum creatinine levels. The free radical markers measured were: thiobarbituric acid reactive substances, glutathione perioxidase, and superoxide dismutase. No significant differences in thiobarbituric acid reactive substances, glutathione peroxidase, or superoxide dismutase, were found between the diabetic smokers and non-smokers. Also, no difference was found comparing the diabetic patients with 40 non-diabetic control subjects (20 smokers). Persistent albuminuria was present in 16 patients (10 microalbuminuria) and free radical marker concentrations in these subjects were similar to the normoalbuminuric patients. This data suggests that any increase in free radical activity due to cigarette smoke is adequately scavenged in young adults with diabetes who are free of significant macrovascular disease.     

丹参对肝硬化上消化道大出血患者体内脂质过氧化状态的影响

目的:探讨肝硬化上消化道大出血患者体内脂质过氧化状态的变化及丹参注射液对其的影响.方法:肝硬化上消化道大出血患者91例,随机分为丹参注射液治组(n=36)和传统治疗组(n=55).分别测定患者血中超氧化物岐化酶(SOD)活性和过氧化脂质(LPO)含量.结果:传统治疗组患者血中LPO含量在出血后明显增加,72h左右达最高峰(11.0±4.1 nmol/L),较出血前或12h内(7.8±3.3 nmol/L)明显升高(P<0.01),1wk后开始下降,4wk后可不同程度恢复.而经丹参注射液治疗的患者血中LPO含量亦于72h左右达最高峰,但变化幅度较小(9.9±4.6nmol/L vs 7.8±3.1nmol/L,P<0.05),恢复较快.两组SOD活性变化与LPO含量变化相反,72h降至最小值(传统治疗组:0.87±0.2 nkat/L vs 1.3±0.2 nkat/L,P<0.01;丹参注射液治组:0.9±0.3 nkat/L vs 1.4±0.2 nkat/L,P<0.01),4 wk后可不同程度恢复.丹参注射液治疗组患者的预后明显优于传统治疗组(P<0.01),且Child-Pugh B级者优于C级(P<0.05).结论:丹参注射液可提高机体的抗氧化能力,改善肝硬化上消化道大出血患者的预后.     

卡氏肺孢子菌肺炎大鼠超氧化物歧化酶和过氧化脂质变化的研究

24只SD大鼠分为卡氏肺孢子菌肺炎感染组(18只)和健康对照组(6只)。感染组以地塞米松磷酸钠3.5mg/(只.次),每周2次,连续8周腹股沟皮下注射SD大鼠,建立卡氏肺孢子菌肺炎动物模型。肺组织印片六亚甲基四胺银染色和肺组织病理切片伊红-苏木素(HE)染色观察实验大鼠肺组织的病理学变化。分光光度法检测肺组织匀浆超氧化物歧化酶(SOD)活力和过氧化脂质(LPO)含量。结果显示,感染组大鼠可见卡氏肺孢子菌包囊并发现典型病理改变;感染组SOD值[(31.49±7.18)U/mgprot]与健康对照组[(54.41±8.97)U/mgprot]相比,差异有统计学意义(P<0.01);感染组LPO值[(2.26±0.21)nmol/mgprott]与健康对照组[(1.63±0.01)nmol/mgprot]相比,差异有统计学意义(P<0.01)。     

不同增龄期雌雄大鼠肝脏与性腺自由基浓度测定

本文利用电子自旋共振技术比较测定了青、中、老年雌雄大鼠肝和性腺自由基浓度,结果表明:老年大鼠的睾丸与卵巢自由基浓度明显低于青年鼠,24月龄雄鼠的肝自由基浓度亦明显低于13月龄鼠。     

丹参粉针剂对高血压病患者氧自由基、纤溶活性、一氧化氮的干预作用

目的：探讨丹参粉针剂对原发性高血压病（EH）患者氧自由基、纤溶活性、一氧化氮的干预作用。方法：测定80例EH患者血浆丙二醛（MDA）、超氧化物歧化酶（SOD）、组织型纤维酶原激活物（t-PA）,t-PA抑制剂（PAI）及一氧化氮（NO）,随机分为常规治疗对照组（40例,予左旋氨氯地平75 mg/d降压治疗）;观察组（40例,在常规治疗对照组的基础上加用丹参粉针剂400mg加入250ml 5%葡萄糖注射液中静脉滴注,1次/d）,治疗2周后测定并比较两组治疗前后MDA、SOD、t-PA、PAI及NO水平的变化。结果：治疗前两组MDA、SOD、t-PA、PAI及NO水平比较无显著性差异（P〉0.05）。常规治疗对照组治疗前后上述指标无显著性差异（P〉0.05）。与治疗前比较,观察组治疗后MDA[（5.66±1.30）μmol/L∶（3.86±0.88）μmol/L]、PAI[（5.67±2.15）AU/ml∶（2.65±1.10）AU/ml]水平明显下降（P〈0.01）,且明显低于常规治疗对照组治疗后水平（P均〈0.01）,而SOD[（87.4±21.6）U/L∶（138.2±18.9）U/L],t-PA[（0.67±0.3）IU/ml∶（1.23±0.46）IU/ml],NO[（7.58±2.66）μmol/L∶（12.86±3.61）μmol/L]水平则明显升高（P〈0.01）,且明显高于常规治疗对照组治疗后水平（P均〈0.01）。结论：丹参粉针剂能提高患者的超氧化物歧化酶活力,降低丙二醛含量,促进纤溶活性及增加一氧化氮合成、释放。     

Experimental study on the pathogenesis of acute acalculous cholecystitis,with special reference to the roles of microcirculatory disturbances,free radicals and membrane-bound phospholipase A2

To elucidate the pathogenesis of acute acalculous cholecystitis, the gallbladder was subjected to ischemia-reperfusion by simultaneously occluding the middle hepatic artery and the superior mesenteric vein in dogs, and the degree of inflammation and biochemical changes in the gallbladder mucosa were studied by varying the duration of ischemia or reperfusion. Ischemia alone did not induce cholecystitis either macroscopically and histologically, although it increased phospholipase A₂ (PIA₂) activity, content of lipid peroxide, and Superoxide dismutase (SOD) activity in the mucosa with prolongation of the ischemic time. Cholecystitis was produced in all animals by 45-min ischemia followed by 90-min reperfusion as the shortest ischemia and reperfusion times. In this model, prolongation of the ischemic time increased the area of mucosal inflammation horizontally with increases of the PIA₂ activity, content of lipid peroxide, and SOD activity, whereas by prolonging the reperfusion time the inflammation area spread deeper vertically toward the serosal side with significant increase in the mucosal PIA₂ activity, content of lipid peroxide, and SOD activity. These results revealed that ischemia-reperfusion plays an important role in the pathogenesis of acute acalculous cholecystitis, causing the generation of free radicals and the activation of membrane-bound PIA₂. Abstracts of this study were presented at the 30th and 31st Annual Meeting of the Japanese Society of Gastroenterology and the 25th Annual Meeting of the Japan Biliary Association.     

Free Radical Formation in Livers of Rats Treated Acutely and Chronically with Alcohol

The spin trapping method was used to assess formation of free radical intermediates in vivo before and after acute alcohol administration to rats. Ascorbyi radicals and spin adducts of dietary alcohol or endogenous compounds, such as lipids, were detected with higher frequency in bile from alcohol-fed rats than in corresponding samples from rats fed control diets. When alcohol was given acutely to these animals, the 1-hydroxyethyl radical metabolite of ethanol was also formed at higher rates in livers of rats that had been fed ethanol chronically. Furthermore, formation of lipid radicals was enhanced after acute alcohol administration. These data support the hypothesis that chronic alcohol administration causes development of oxi-dative conditions in the liver, which subsequently lead to formation of differing types of radicals. Liver microsomes from alcohol-fed rats also metabolized ethanol to the 1-hydroxyethyl radical at higher rates than controls.     

清热化瘀汤对老年胃食管反流病患者血清超氧化物歧化酶及脂质过氧化物的影响

目的:观察清热化瘀汤治疗对老年胃食管反流病患者血清超氧化物歧化酶(SOD)及脂质过氧化物(LPO)的影响.方法:将160例老年胃食管反流病患者随机分为观察组(n=80)和对照组(n=80),分别给予内服清热化瘀汤和口服西药治疗.治疗前后分别检测血清SOD(双抗体法)和LPO(硫代巴比妥酸法)的含量,并用t检验方法进行统计学分析.结果:治疗后两组SOD含量均呈上升趋势,但观察组明显上升,且接近正常值水平,与对照组比较有显著性差异(26.01±2.56 kU/L vs 23.02±2.54 kU/L,P<0.05);治疗后两组LPO含量均呈下降趋势,但观察组明显下降,且接近正常值水平,与对照组比较差异显著(4.19±0.52 mol/L vs 4.96±1.13 mol/L,P<0.05).结论:清热化瘀汤治疗胃食管反流病,具有明显改善自由基代谢紊乱的作用.     

Modulation of Nitric Oxide Synthase Activity in Brain,Liver, and Blood Vessels of Spontaneously Hypertensive Rats by Ascorbic Acid: Protection from Free Radical Injury

End organ damage in essential hypertension has been linked to increased oxygen free radical generation, reduced antioxidant defense, and/or attenuation of nitric oxide synthase (NOS) activity. Ascorbic acid (AA), a water-soluble antioxidant, has been reported as a strong defense against free radicals in both aqueous and nonaqueous environment. In this study we examined the hypothesis that antioxidant ascorbic acid may confer protection from increased free radical activity in brain, liver, and blood vessels of spontaneously hypertensive rats (SHR). Male SHRs were divided into groups: SHR + AA (treated with AA, 1 mg/rat/day; for 12 weeks) or SHR (untreated). Wister-Kyoto rats (WKY) served as the control. Mean systolic blood pressure (SBP) in treated and untreated SHR was 145 ± 7 mmHg and 142 ± 8 mmHg, respectively. AA treatment prevented the increase in systolic blood pressure in SHR by 37 ± 1% (p < 0.05). NOS activity in the brain, liver, and blood vessels of WKY rat was 1.82 ± 0.02, 0.14 ± 0.003, and 1.54 ± 0.06 pmol citruline/mg protein, respectively. In SHR, total NOS activity was significantly reduced by 52 ± 1%, 21 ± 3%, and 44 ± 4%, respectively. AA increased NOS activity in brain, liver, and blood vessels of SHR from 0.87 ±.03, 0.11 ±.01, and 0.87 ±.08 pmol citruline/mg protein to 0.93 ± 0.01, 0.13 ± 0.001, and 1.11 ± 0.03 pmol citruline/mg protein (p < 0.05), respectively. Lipid peroxides in the brain, liver, and blood vessels from WKY rats were 0.87 ± 0.06, 0.11 ± 0.005, and 0.47 ± 0.04 nmol MDA equiv/mg protein, respectively. In SHR, lipid peroxides in brain, liver, and blood vessels were significantly increased by 40 ± 3%, 64 ± 3%, and 104 ± 13%, respectively. AA reduced lipid peroxidation in liver and blood vessels by 17 ± 1% and 34 ± 3% but not in brain. Plasma lipid peroxides were almost doubled in SHR (p < 0.01) together with a reduction in total antioxidant status (6 ± 0.1%; p < 0.05), nitrite (53 ± 2%; p < 0.05) and superoxide dismutase (SOD) activity (36 ± 2%; p < 0.05). AA treatment reduced plasma lipid peroxide (p < 0.001), and increased TAS (p < 0.001), nitrite (p < 0.001), and SOD activity (p < 0.001). From this study, we conclude that brain, liver, and blood vessels in SHR are susceptible to free radical injury, which reduces the availability of NO either by scavenging it or by reducing its production via inhibiting NOS. In addition, brain, liver, and blood vessels in SHR; may be protected by antioxidant, which improves total antioxidant status, and SOD thus may prevent high blood pressure and its complications.