养心颗粒对急性心肌梗死犬血管内皮细胞及心肌损伤的保护作用

目的观察养心颗粒(YXG)对急性心肌梗死犬血管内皮细胞及心肌损伤的保护作用。方法采用结扎冠脉前降支的方法,复制急性心肌梗死模型。分别测定冠脉结扎前以及药后不同时间点血浆超氧化物歧化酶(SOD)、丙二醛(MDA)、内皮素(ET)、一氧化氮(NO)、P-选择素及肌酸磷酸激酶同工酶(CK-MB)的变化。采用N-BT染色法测定心肌梗死面积。结果YXG治疗组与模型组比较,血浆CK-MB、MDA、ET、P-选择素降低(P<0.05~0.01),而血浆SOD和NO升高(P<0.05~0.01),梗死面积明显缩小(P<0.01)。结论YXG对急性心肌梗死犬心肌及血管内皮细胞的损伤具有保护作用,其作用机制可能与抗氧化、改善血管内皮细胞的分泌功能及抑制血小板活化有关。     

Aliskiren protects against myocardial ischaemia‐reperfusion injury via an endothelial nitric oxide synthase dependent manner

Aliskiren, a direct renin inhibitor, has shown potent ability to attenuate hypertension. Our previous research has found that aliskiren protected against myocardial ischaemia‐reperfusion (I/R) injury and enhanced phosphorylation of endothelial nitric oxide synthase (eNOS) in spontaneously hypertensive rats. However, whether the cardioprotective effect of aliskiren against myocardial I/R injury was eNOS‐dependent is unknown. In the present study, 12‐week‐old male eNOS knockout (eNOS^?/?) and wild‐type C57BL/6J mice (WT) were orally administrated with the dose of 50 mg/kg per day of aliskiren. After a 4‐week treatment, aliskiren decreased blood pressure in eNOS^?/? mice, and reduced renin‐angiotension II levels in both eNOS^?/? and WT mice. Aliskiren also improved left ventricular ejection fraction (EF) and fractional shortening (FS), decreased myocardial infarct size, reduced creatine kinase (CK) and lactate dehydrogenase (LDH) activity in plasma, attenuated dihydroethidium (DHE) fluorescence and levels of malondialdehyde (MDA), enhanced superoxide dismutase (SOD) activity and total antioxidant capacity (T‐AOC) in myocardium, increased SOD and thioredoxin (Trx) proteins expression in WT mice subjected to 30 minutes of ischaemia followed by reperfusion for 24 hours. However, aliskiren failed to restore all of the above indices in eNOS^?/? mice subjected to the same I/R injury. Our study indicated that aliskiren protected against myocardial I/R injury via an eNOS dependent manner.     

Protective effects of hydroxysafflor yellow A on acute and chronic congestive cardiac failure mediated by reducing ET-1, NOS and oxidative stress in rats

The present study was conducted to investigate whether hydroxysafflor yellow A (HSYA) has a protective effect on acute and chronic heart failure (AHF/CHF) induced by ligation of the left anterior descending coronary artery for 3 h and 8 weeks, respectively. The rats were divided into the following groups: sham operation, coronary artery ligation (CAL), CAL+HSYA (100 mg kg(-1) by gavage) and CAL+diltiazem (20 mg kg(-1) by gavage). In the AHF model, heart function, as determined by haemodynamic studies and echocardiography, was improved significantly by pretreatment with HSYA or diltiazem. Significant reductions in elevated serum creatine phosphokinase, lactate dehydrogenase, malondialdehyde (MDA), glutamic oxalacetic transaminase, glutamic pyruvic transaminase and blood viscosity were observed, and the activity of serum superoxide dismutase (SOD) was enhanced (all P<0.01). In the CHF model, HSYA and diltiazem restored abnormal heart function, and completely suppressed the elevated plasma atrial natriuretic polypeptide (ANP) and endothelin-1 (ET-1), serum and left-ventricular tissue inducible nitric oxide (NO) synthase (iNOS), NO and MDA, and improved the decrease in SOD. HSYA and diltiazem improved cardiac performance in AHF and reduced cardiac remodelling in CHF by reducing tissue weight indices: left ventricular weight/body weight (BW), right ventricular weight/BW, kidney weight/BW and lung weight/BW, and attenuating increases in infarct size, inner diameter of the left ventricle and collagen volume fraction in non-infarcted areas, and the decrease in mean wall thickness of infarcted myocardium. These results suggest that HSYA exerted beneficial actions in cardiac performance in models of both AHF and CHF, mainly by suppressing ET-1, iNOS and oxidative stress in infarcted tissue.     

A reduction of endogenous asymmetric dimethylarginine contributes to the effect of captopril on endothelial dysfunction induced by homocysteine in rats

We examined whether captopril exerts beneficial effect on homocysteine-induced endothelial dysfunction in vivo and whether this effect of captopril is associated with a reduction of endogenous inhibitor of nitric oxide synthase (NOS) asymmetric dimethylarginine (ADMA) in rats. Male Sprague-Dawley rats were given intravenous injections of homocysteine (10 mg/kg/day) to induce endothelial dysfunction. Captopril treatment (3 mg/kg/day, i.v.) was taken in some rats after homocysteine administration. Endothelium-dependent relaxation was tested in aortic rings. Serum levels of ADMA, nitrite/nitrate, malondialdehyde (MDA), and creatinine were measured. Furthermore, superoxide dismutase activity in liver and angiotensin converting enzyme activity in serum were also assayed. Administration of homocysteine to rats for 4 weeks significantly impaired endothelium-dependent relaxation compared with control rats. This impairment of endothelium-dependent relaxation was accompanied by elevated serum concentration of ADMA and decreased serum content of nitrite/nitrate. Moreover, serum concentration of MDA was remarkably increased, whereas liver superoxide dismutase activity was decreased in homocysteine-treated group compared with control. Chronic captopril treatment not only improved the impaired endothelium-dependent relaxation, but also prevented the elevation of serum ADMA and MDA levels, as well as reduction of serum nitrite/nitrate contents and liver superoxide dismutase activity. Serum angiotensin converting enzyme activity and creatinine had no significant difference between the three groups. These results suggest that chronic captopril treatment reduces endogenous inhibitor of NOS in rats with homocysteine injection, which may contribute to the beneficial effect of captopril on homocysteine-induced endothelial dysfunction in vivo, and may be secondary to the antioxidative action of captopril.     

Wine polyphenols induce hypotension, and decrease cardiac reactivity and infarct size in rats: involvement of nitric oxide

1. The effects of short-term oral administration of red wine polyphenolic compounds (RWPC, 20 mg x kg(-1) day(-1) for 7 days) on haemodynamics, ex vivo cardiac responsiveness and ischaemia-reperfusion injury were investigated in rats. The involvement of nitric oxide (NO) was evaluated using the NO synthase inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME, 2 mg x kg(-1) day(-1) for 7 days), at a dose which did not affect blood pressure. 2. Ex vivo reactivity of hearts from RWPC-treated rats showed lower basal developed pressure, greater heart rate and decreased inotropic responses to either beta-adrenoceptor or muscarinic receptor stimulation with isoprenaline or carbachol, respectively.3. RWPC treatment did not modify cardiac expression of endothelial NO synthase or Cu/Zn superoxide dismutase. However, it increased nitrite in the coronary effluent. 4. In ischaemia-reperfusion, RWPC treatment reduced infarct size and oxidative stress, as shown by the myocardial content of the end products of lipid peroxidation, malondialdehyde and 4-hydroxynonenal, without affecting post-ischaemic contractile dysfunction. All the observed effects of RWPC were prevented by l-NAME treatment. 5. Altogether, these data show that short-term treatment with RWPC decreases blood pressure and cardiac responsiveness, and protects against post-ischaemic infarction via decreased oxidative stress. All the above effects of RWPC are sensitive to NO synthase inhibition that implies an involvement of NO-dependent pathway. This study suggests a basis for the beneficial effects of plant-derived polyphenols against cardiovascular disease.     

Protective effects of apricot kernel oil on myocardium against ischemia–reperfusion injury in rats

The present study was undertaken to evaluate the potential cardioprotective effects of apricot kernel oil (AO) on the myocardial ischemia–reperfusion (IR) of rat model in vivo. The rats were divided into five groups: sham-operated, IR, low dose AO-treated IR (LD-AO + IR), medium dose AO-treated IR (MD-AO + IR) and high dose AO-treated IR (HD-AO + IR). All rats were provided with food and water ad libitum. The LD-AO + IR, MD-AO + IR and HD-AO + IR groups were given a daily dose of 2, 6 and 10 ml kg⁻¹ BW⁻¹ of AO, respectively, for 14 days prior to the IR operation. Tetrazolium chloride staining revealed that infarct size and the ratio of infarct weight to the total heart weight were decreased significantly in the three AO-treated groups compared to the IR group. The serum creatine kinase and aspartate aminotransferase activities also demonstrated similar beneficial effects. Myocardial catalase, superoxide dismutase, glutathione peroxidase, and constitutive nitric oxide synthase activities, as well as NO concentrations, were all increased, whereas malondialdehyde content and inducible nitric oxide synthase were decreased in AO-treated rats. These findings suggest that apricot kernel oil has potent cardioprotective effects, and could be developed as a nutriment for the treatment and prevention of myocardial infarcts.     

Melatonin and Vitamin C Attenuates Alcohol‐Induced Oxidative Stress in Aorta

Abstract: Epidemiological studies have shown that low to moderate doses of alcohol consumption are beneficial to cardiac health. However, chronic high doses of alcohol ingestion cause cardiovascular complications. The aim of this study was to investigate both the effects of melatonin and vitamin C and expression of endothelial nitric oxide synthase in aorta of chronic alcoholic rats. Twenty‐four adult male Wistar rats weighing 200–250 g were used in the study. Rats were divided into four equal groups. Group I (control): rats were not fed on alcohol; Group II: rats were fed on alcohol; Group III: rats were fed on alcohol and 40 mg/kg vitamin C were injected intraperitoneally and Group IV: rats were fed on alcohol and 4 mg/kg melatonin were injected intraperitoneally. At the end of the experiment, rats were killed and aorta tissues were removed. Some parts of the aorta tissues were used for biochemical analyses and the other parts were used at histological procedures. In the control group, endothelial nitric oxide synthase immunoreactivity was (++) in smooth muscle cells and endothelial cells. Expression of endothelial nitric oxide synthase in the alcohol group was stronger than control group. Chronic ethanol ingestion significantly increased (p < 0.05); and melatonin significantly decreased both the plasma and tissue malondialdehyde levels. The superoxide dismutase levels and catalase activity did not change significantly in the Vitamin C and melatonin groups (p > 0.05) compared to the control and alcohol groups. The present results indicate that chronic alcohol consumption increase lipid peroxidation and cause endothelial nitric oxide synthase expression in the aorta. However, melatonin and vitamin C administration provide partial protection against alcohol‐induced damage.     

Coconut kernel protein in diet protects the heart by beneficially modulating endothelial nitric oxide synthase,tumor necrosis factor-alpha,and nuclear factor-kappaB expressions in experimental myocardial infarction

Previous studies conducted in our laboratory revealed that coconut kernel protein has a significant cardioprotective effect on isoproterenol-induced myocardial infarction in rats. In the present study, we explored the possible protective mechanism of coconut kernel protein during acute myocardial infarction. Coconut kernel protein (50 mg/100 g) was administered to Sprague-Dawley rats orally for 45 days. Isoproterenol (20 mg/100 g) was injected subcutaneously at an interval of 24 hours twice to induce myocardial infarction. Myocardial infarction was confirmed by the abnormal activities of cardiac marker enzymes in serum. Activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase were decreased (p < 0.05) in the heart of isoproterenol-treated rats, whereas pretreatment with coconut kernel protein increased (p < 0.05) these activities. An improved antioxidant status in these rats was further confirmed by the increased level of reduced glutathione and decreased level of lipid peroxidation products. Nitric oxide synthase (NOS) activity in the heart and nitrite level in blood were increased (p < 0.05) in coconut kernel protein-treated rats administered with isoproterenol compared to isoproterenol control rats. Coconut protein pretreatment upregulated the expression of endothelial nitric oxide synthase (eNOS), whereas expressions of nuclear factor-kappaB (NF-κB) and tumor necrosis factor-alpha (TNF-α) were downregulated in isoproterenol-treated rats. These findings suggest that the protective effects of coconut kernel protein may be mediated in part through upregulation of nitric oxide production, antioxidant mechanisms, and its ability to inhibit TNF-α and NF-κB activation.     

Delayed or second window preconditioning induced by adenosine A1 receptor activation is independent of early generation of nitric oxide or late induction of inducible nitric oxide synthase

Transient adenosine A1 receptor (A1R) activation induces a second window or delayed preconditioning against myocardial infarction 24-72 h later. Early generation of nitric oxide and delayed induction of nitric oxide synthase have been implicated in mediating delayed cardioprotection after ischemic preconditioning in rabbits. Recent evidence indicates that some of the regulatory roles of adenosine in cardiac tissue may be mediated by A1R-induced generation of nitric oxide. This study examined the role of nitric oxide in the mediation of A1R-induced delayed preconditioning against infarction. Pharmacologic preconditioning of rabbits with the selective A1R agonist 2-chloro-N6-cyclopentyladenosine 100 microg/kg (CCPA) significantly reduced myocardial infarct size compared with control animals, after 30 min regional ischemia and 2 h reperfusion in vivo 24 h later (27.3+/-4.7 vs. 46.0+/-3.7%, respectively; p = 0.001). Nonselective inhibition of nitric oxide synthase with N(G)-nitro-L-arginine methyl ester (10 mg/kg) before administration of CCPA did not affect this infarct limitation at 24 h. Selective inhibition of inducible nitric oxide synthase before the prolonged ischemic insult on day 2, with two structurally independent inducible nitric oxide synthase inhibitors, L-N(6)-(1-iminoethyl)-lysine (10 mg/kg) or aminoguanidine (300 mg/kg), did not abrogate the reduction in infarction observed by pharmacologic preconditioning with CCPA 24 h earlier. These results suggest that the second window or delayed protection against myocardial infarction observed 24 h after pharmacologic preconditioning with an adenosine A1 agonist occurs independently of either early generation of nitric oxide or subacute induction of inducible nitric oxide synthase.     

1,6-二磷酸果糖对糖尿病大鼠心肌超微结构及氧化应激的影响

目的 观察1,6-二磷酸果糖（FBP）对糖尿病大鼠心肌超微结构、氧化应激的影响.方法 将25只8周龄SPF级健康雄性SD大鼠按抽签法选择19只建立SD大鼠糖尿病模型,余下6只作为正常组.将造模成功的大鼠完全随机分成糖尿病组和FBP干预组（干预组,FBP 500 mg/kg·d腹腔注射）,糖尿病组及正常组给予等量生理盐水腹腔注射.1个月后处死大鼠,取心肌组织进行透射电镜（TEM）观察,并测定心肌组织内氧化应激指标后进行比较.结果 与正常组相比,糖尿病组大鼠心肌肌原纤维断裂,线粒体增多、空泡变性,毛细血管基底膜电子密度增加;丙二醛（MDA）含量、一氧化氮合成酶（NOS）及诱导性一氧化氮合成酶（iNOS）活性增加[（26.65±7.09）nmol/mg比（8.65±2.81）nmol/mg,（651.50±221.10）U/mg比（162.69±70.50）U/mg,（20.22±7.91）U/mg比（5.56±2.06）U/mg,P＜0.05].而干预组NOS及iNOS较糖尿病组降低（P＜0.05）.结论 FBP可以通过减轻氧化应激,减轻线粒体损伤,保护糖尿病大鼠心肌.     

The Effect of 17-methoxyl-7-hydroxy-benzene-furanchalcone Isolated from Millettia pulchra on Myocardial Ischemia In Vitro and In Vivo

The effect of 17-methoxyl-7-hydroxy-benzene-furanchalcone isolated from the roots of Millettia pulchra (Benth.) Kurz var. Laxior (Dunn) Z. Wei on rat myocardial ischemia has been investigated. An in vitro cardiocyte apoptosis model and an in vivo myocardial ischemia model were used to elucidate the mechanism of 17-methoxyl-7-hydroxy-benzene-furanchalcone. In contrast to hydrogen peroxide (H2O2, 100 μmol/L), 17-methoxyl-7-hydroxy-benzene-furanchalcone in vitro (255 and 510 μmol/L) increased the quantity of total superoxide dismutase and the protein expression of B cell lymphoma/leukemia-2, while it inhibited cardiocyte apoptosis, the release of malondialdehyde and tumor necrosis factor α, and protein expression of nuclear factor κ Bp65 and Bcl-2-associated X protein. Furthermore, pretreatment with MHBFC in vivo (10 and 20 mg/kg) decreased heart rate, systolic pressure, diastolic pressure, average pressure, left ventricular systolic pressure, the largest upstroke velocity of the left ventricular pressure (+ dp/dtmax), total antioxidative capability, myoglobin isoenzyme of creatine kinase, and inducible nitric oxide synthase, while it increased endothelial nitric oxide synthase, ATPases, left ventricular diastolic pressure, left ventricular end-diastolic pressure, the largest descendent velocity of the left ventricular pressure (-dp/dtmax) and the interval from the beginning of left ventricular contraction to +dp/dtmax (t - dp/dtmax), all in a dose-dependent manner. Our present results suggest that 17-methoxyl-7-hydroxy-benzene-furanchalcone is an attractive antimyocardial ischemia agent mostly because of its negative heart rate and negative inotropic effects, the reduction in myocardial oxidative damage, and the modulating expression of genes associated with apoptosis, which improves diastolic function.     

乌司他丁对心肌缺血再灌注损伤NO、TNF-a、cTnI浓度的影响

目的观察乌司他丁（ulinastatin,UTI）对心肌缺血再灌注（ischemia reperfusion,I/R）损伤NO、TNF-a、cTnI浓度的影响,研究其机制。方法将24只新西兰大白兔不拘雌雄随机分为假手术组（shame组）,I/R组和UTI组,每组8只。分别于缺血前、缺血30min、再灌注30min、再灌注120min等4个时间点抽动脉血送做分离血清测血清超氧化物岐化酶（superoxide dismutaseSOD）、丙二醛（malondialdehyde MDA）、一氧化氮（nitric oxide NO）、TNF-a、cTnI浓度。结果经30min缺血、120min再灌注后,UTI组与I/R组血清SOD、NO均下降,MDA、TNF-a、cTnI均升高。UTI组与I/R组比较,SOD、NO下降减少,MDA、TNF-a、cTnI升高减少,差异具有统计学意义（P〈0.O5）。结论 UTI可降低心肌缺血再灌注损伤SOD、NO的下降,减少MDA、TNF-a、cTnI的生成。其机制可能是通过增加内源性一氧化氮的含量,抑制肿瘤坏死因子表达,清除氧自由基,从而达到心肌细胞保护性效果。     

Protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-d-glucoside, an active component of Polygonum multiflorum Thunb, on experimental colitis in mice

Reactive oxygen metabolites (ROMs) and inducible nitric oxide synthase (iNOS) are involved in pathogenesis of inflammatory bowel disease. In this study, we examined the effects of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG), an active component extracted from Polygonum multiflorum Thunb, on acetic acid-induced acute colitis and mitomycin C-induced chronic colitis. The inflammatory degree was assessed by histology and myeloperoxidase (MPO) activity. Nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined with biochemical methods. In addition, inducible nitric oxide synthase (iNOS) expression was immunohistochemically studied. In acetic acid-induced acute model, THSG (60 and 120 mg/kg) significantly ameliorated colon damage, inhibited the increase of acetic acid-induced MPO activity, depressed MDA and NO level, and enhanced SOD activity. Moreover, the effects of 120 mg/kg THSG were better than that of positive control drug, 5-aminosalicylic acid (5-ASA). In mitomycin C-induced model, THSG (60 mg/kg) administered for 7 days and 24 days, significantly improved colon damage and inhibited MPO activity and MDA content while increased SOD activity only on the 7th day and debased NO level on the 24th day. Furthermore, on the 24th day, the effects of THSG were prior to that of 5-ASA. Additionally, THSG (60 mg/kg) could inhibit iNOS expression in both models. In conclusion, THSG exerts protective effects on experimental colitis through alleviating oxygen and nitrogen free radicals level and down-regulating iNOS expression.     

重组人超氧化物歧化酶在大鼠和小鼠的抗炎作用及机理研究

目的:研究重组人超氧化物歧化酶(rhSOD)的抗炎作用及其作用机理.方法:采用角叉菜胶诱导的大鼠和小鼠关节炎、巴豆油诱发的小鼠耳肿模型,研究药物对炎症肿胀度的影响.大鼠炎症渗出液中NOS活性用NADPH黄递酶染色法、β-NAG用对硝基酚比色法、MDA用TBA荧光法测定,IL-1β和TNFα含量用放射免疫法测定.结果:rhSOD 20-80mg/kg ip对大鼠关节炎,10-80mg/kg im对小鼠耳肿、80mg/kg ip对小鼠足肿有显著的抑制作用.同时大鼠炎症渗出液中NOS活性降低,IL-1β和TNFα含量显著减少.其抑制IL-1β中成的作用明显强于地塞术松2mg/kg ip.rhSOD使炎症组织内中性粒细胞浸润减轻,MDA生成减少,闲不影响炎症渗出液中β-NAG活性.结论:rhSOD对大鼠和小鼠实验性炎症有明显的抗炎作用.其抗炎作用机理和清除氧自由基、抗脂质过氧化有关,也和抑制炎症细胞浸润、减少炎症性细胞因子如IL-1β和TNFα的生成有关.     

Aliskiren improves endothelium‐dependent relaxation of thoracic aorta by activating PI3K/Akt/eNOS signal pathway in SHR

Aliskiren, a direct renin blocker, has been approved for the treatment of hypertension. However, the potential role of aliskiren on vascular endothelial function in spontaneously hypertensive rats (SHR) remains unclear. In the present study, male SHRs at 12 weeks of age were orally administrated 30 mg/kg per day or 60 mg/kg per day aliskiren. After a 4‐week treatment, aliskiren showed a significant effect on the reduction of blood pressure at a dosage of 60 mg/kg per day, but not of 30 mg/kg per day. Moreover, both dosages of aliskiren improved endothelium‐dependent relaxation, reduced dihydroethidium fluorescence intensity, decreased level of malondialdehyde but heightened total antioxidant capacity and superoxide dismutase activity in thoracic aorta in SHR. Aliskiren also markedly increased expression of p85α, an important subunit of phosphatidylinositol 3 kinase (PI3K), enhancing phosphorylation of protein kinase B (Akt) at Ser473 and endothelial nitric oxide synthase (eNOS) at Ser1177, as well as cyclic guanosine‐3′5′‐monophosphate (cGMP, a sensitive index of biological activity of nitric oxide) concentration. Furthermore, both anti‐oxidative and endothelium protective effects of aliskiren were diminished when PI3K was inhibited in vivo. The data presented here indicates that, aliskiren improves endothelium‐dependent relaxation of thoracic aorta in SHR, predominantly through attenuating oxidative stress and activation of the PI3K/Akt/eNOS pathway. These data might propose novel strategies to prevent and improve vascular endothelial dysfunction.     

Protective effect of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino) propane hydrochloride on myocardial ischemia-reperfusion injury in rats

The aim of the present study was to investigate the protective effect of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino) propane hydrochloride (DDPH) on myocardial ischemia-reperfusion (I/R) injury in rats and the mechanism of its myocardial protection. For this purpose, 50 Wistar rats were divided into five groups: sham group, control group, verapamil treated group, and two DDPH treated groups (20 and 40 mg/kg, respectively). Myocardial I/R injury model was established by reperfusion for 120 min after 40 min ischemia induced by the ligation of left descending coronary artery in rats. The influence of DDPH on myocardial infarction size was observed and the levels of myocardial enzymes in serum were measured. The activities of oxygen free radical scavenging enzymes and the content of malondialdehyde (MDA) in myocardium and serum were determined. The pathological changes of myocardial tissue were observed. The results showed that DDPH significantly diminished myocardial infarction size, reduced the release of myocardial creatine phosphokinase (CPK), lactate dehydrogenase (LDH) and glutamic oxaloacetic aminotransferase (GOT), protected the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and decreased the content of MDA in myocardium and serum as compared with the control group. The degree of myocardial injury was slighter in DDPH treated groups than in control group. These results suggest that DDPH produces a cardioprotective effect during myocardial I/R injury, which may be related to blocking calcium channels and inhibiting the formation of the oxygen free radical and subsequent peroxidation of lipid by DDPH.     

Hippophae rhamnoides attenuates nicotine-induced oxidative stress in rat liver

The effects of vitamin E and Hippophae rhamnoides L. (Elaeagnaceae) extract (HRe-1) on nicotine-induced oxidative stress in rat liver were investigated. Four groups, eight rats each, were used in this study, and the supplementation period was 3 weeks. The groups were: nicotine (0.5?mg/kg/day, intraperitoneal (i.p.)); nicotine plus vitamin E (75?mg/kg/day, intragastric (i.g.)); nicotine plus HRe-1 (250?mg/kg/day, i.g.); and the control group. The malondialdehyde and nitric oxide levels, glutathione peroxidase, glutathione S-transferase, glutathione reductase, superoxide dismutase, and total and non-enzymatic superoxide scavenger activities were measured spectrophotometrically in supernatants of the tissue homogenates. Nicotine increased the malondialdehyde level in liver tissue compared with control. This nicotine-induced increase in lipid peroxidation was prevented by both vitamin E and HRe-1. Superoxide dismutase activity was higher in the nicotine plus vitamin E-supplemented group compared with nicotine and control groups. Glutathione reductase activity was higher in the nicotine group compared with the control group. However, glutathione peroxidase activity in the control group was higher than the levels in the nicotine, and the nicotine plus HRe-1 supplemented groups. The nitric oxide level was higher in the nicotine group compared with all other groups. Total and non-enzymatic superoxide scavenger activities and glutathione S-transferase activity were not affected by any of the treatments. Our results suggest that Hippophae rhamnoides extract as well as vitamin E can protect the liver against nicotine-induced oxidative stress.     

Protect effect of bicyclol on cisplatin-induced nephrotoxicity in mice

This study investigated the protective effects of bicyclol against cisplatin-induced nephrotoxicity and the possible mechanisms in mice. Bicyclol (250 mg/kg, p.o., 5 days) showed significant protection as evidenced by the decrease of elevated serum creatine and blood urea nitrogen, and improvement of histopathological injury induced by cisplatin. The formation of kidney malondialdehyde with a concomitant reduction of reduced glutathione were also inhibited by bicyclol, while the activities of kidney superoxide dismutase, catalase and glutathione peroxidase were all increased, respectively. Bicyclol also inhibited the increase of kidney and serum nitric oxide induced by cisplatin. In addition, induction of induced nitric oxide synthase and nitrotyrosine were suppressed by bicyclol. Bicyclol suppressed cisplatin-induced extracelluar signal regulated kinases 1/2 and p38 mitogen-activated protein kinase activation in the kidney of mice. Results obtained demonstrate that bicyclol pre-administration can prevent the nephrotoxicity induced by cisplatin.     

PNU282987对异丙肾上腺素所致小鼠心脏重塑的保护作用

目的通过建立异丙肾上腺素所致小鼠心脏重塑模型,观察PNU282987保护心脏的作用。方法连续7 d皮下注射异丙肾上腺素(ISO),诱导小鼠心脏重塑模型,同时腹腔给予PNU282987,检测小鼠心脏重量指数、血清乳酸脱氢酶(LDH)和肌酸激酶(CK)的活性,观察心肌病理形态学的改变;检测心肌组织中超氧化物歧化酶(SOD)和丙二醛(MDA)的含量,通过Western blot测定诱导型一氧化氮合酶(iNOS)的表达。结果与正常对照组相比,异丙肾上腺素组心脏重量指数增加,血清LDH和CK水平显著升高,心肌SOD活性下降,MDA含量增加,心肌组织中iNOS蛋白表达增加;与模型组比较,PNU282987可显著降低心脏重量指数、血清LDH和CK水平,增加心肌SOD活性,降低心肌MDA含量,下调iNOS表达。结论 PNU282987可能通过清除氧自由基,降低iNOS的表达,保护异丙肾上腺素导致的小鼠心脏重塑。