芝麻素对2型糖尿病大鼠主动脉内皮功能的保护作用

目的探讨芝麻素改善2型糖尿病大鼠主动脉内皮功能损伤的作用及可能机制。方法采用长期高脂饮食加小剂量链脲佐菌素(streptozotocin,STZ)建立2型糖尿病大鼠模型。灌服不同剂量芝麻素(120、60 mg.kg-1.d-1)8周后处死动物。离体血管灌流法测大鼠主动脉内皮依赖性舒张反应及NO生物活性,测血清丙二醛(malondialdehyde,MDA)含量和总抗氧化能力(total antioxidative capacity,T-AOC),Western blot测主动脉内皮型一氧化氮合酶(endothelial nitricoxide synthase,eNOS)、硝基酪氨酸(nitrotyrosine,NT)和还原型辅酶Ⅱ(NADPH)氧化酶亚基P47phox蛋白表达。结果与模型组相比,芝麻素(120 mg.kg-1.d-1)组内皮依赖性血管舒张功能增强,NO活性升高;血清MDA含量降低,T-AOC水平升高;主动脉eNOS蛋白表达增高,NT和P47phox蛋白表达降低。结论芝麻素可改善糖尿病大鼠血管内皮功能,其机制与上调血管eNOS表达和减轻NO氧化失活有关。     

Metformin restores endothelial function in aorta of diabetic rats

BACKGROUND AND PURPOSE

The effects of metformin, an antidiabetic agent that improves insulin sensitivity, on endothelial function have not been fully elucidated. This study was designed to assess the effect of metformin on impaired endothelial function, oxidative stress, inflammation and advanced glycation end products formation in type 2 diabetes mellitus.

EXPERIMENTAL APPROACH

Goto-Kakizaki (GK) rats, an animal model of nonobese type 2 diabetes, fed with normal and high-fat diet during 4 months were treated with metformin for 4 weeks before evaluation. Systemic oxidative stress, endothelial function, insulin resistance, nitric oxide (NO) bioavailability, glycation and vascular oxidative stress were determined in the aortic rings of the different groups. A pro-inflammatory biomarker the chemokine CCL2 (monocyte chemoattractant protein-1) was also evaluated.

KEY RESULTS

High-fat fed GK rats with hyperlipidaemia showed increased vascular and systemic oxidative stress and impaired endothelial-dependent vasodilatation. Metformin treatment significantly improved glycation, oxidative stress, CCL2 levels, NO bioavailability and insulin resistance and normalized endothelial function in aorta.

CONCLUSION AND IMPLICATIONS

Metformin restores endothelial function and significantly improves NO bioavailability, glycation and oxidative stress in normal and high-fat fed GK rats. This supports the concept of the central role of metformin as a first-line therapeutic to treat diabetic patients in order to protect against endothelial dysfunction associated with type 2 diabetes mellitus.     

Methylglyoxal promotes oxidative stress and endothelial dysfunction

Modern diets can cause modern diseases. Research has linked a metabolite of sugar, methylglyoxal (MG), to the development of diabetic complications, but the exact mechanism has not been fully elucidated. The present study was designed to investigate whether MG could directly influence endothelial function, oxidative stress and inflammation in Wistar and Goto-Kakizaki (GK) rats, an animal model of type 2 diabetes. Wistar and GK rats treated with MG in the drinking water for 3 months were compared with the respective control rats. The effects of MG were investigated on NO-dependent vasorelaxation in isolated rat aortic arteries from the different groups. Insulin resistance, NO bioavailability, glycation, a pro-inflammatory biomarker monocyte chemoattractant protein-1 (MCP-1) and vascular oxidative stress were also evaluated. Methylglyoxal treated Wistar rats significantly reduced the efficacy of NO-dependent vasorelaxation (p<0.001). This impairment was accompanied by a three fold increase in the oxidative stress marker nitrotyrosine. Advanced glycation endproducts (AGEs) formation was significantly increased as well as MCP-1 and the expression of the receptor for AGEs (RAGE). NO bioavailability was significantly attenuated and accompanied by an increase in superoxide anion immunofluorescence. Methylglyoxal treated GK rats significantly aggravated endothelial dysfunction, oxidative stress, AGEs accumulation and diminished NO bioavailability when compared with control GK rats. These results indicate that methylglyoxal induced endothelial dysfunction in normal Wistar rats and aggravated the endothelial dysfunction present in GK rats. The mechanism is at least in part by increasing oxidative stress and/or AGEs formation with a concomitant increment of inflammation and a decrement in NO bioavailability. The present study provides further evidence for methylglyoxal as one of the causative factors in the pathogenesis of atherosclerosis and development of macrovascular diabetic complication.     

葡萄籽原花青素对2型糖尿病大鼠血清中SOD GSH MDA及NO表达的影响

目的观察葡萄籽原花青素(GSPE)对2型糖尿病大鼠血清中超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)、丙二醛(MDA)及一氧化氮(NO)表达的影响。方法选取SPF级雄性SD大鼠30只,出生180d,体质量180～220g,高脂饲料喂养4周后再小剂量腹腔注射链脲佐菌素(STZ)诱导2型糖尿病模型,随机分为糖尿病对照组,GSPE250mg·kg-1·d-1、50mg·kg-1·d-1剂量干预组;另设6只为普食对照组。检测各组喂养第6周、10周后的血糖水平,并检测第10周后大鼠血清中SOD、MDA、GSH及NO的变化。结果GSPE能降低血糖,但效果不明显。在抗氧化指标的检测中,与糖尿病对照组相比,GSPE250mg·kg-1·d-1剂量干预组SOD、GSH明显升高(P<0.05),MDA、NO明显降低(P<0.05);50mg·kg-1·d-1剂量干预组SOD、GSH有所升高,MDA、NO有所降低,但差异无统计学意义(P>0.05)。结论较高剂量的GSPE能有效改善2型糖尿病大鼠的抗氧化能力,对其作用机制的进一步研究,可为GSPE对糖尿病及其并发症的营养干预治疗提供新的思路和依据。     

Sesamin exerts renoprotective effects by enhancing NO bioactivity in renovascular hypertensive rats fed with high-fat-sucrose diet

In the present study, we aimed to evaluate the protective effect of sesamin on kidney damage and renal endothelial dysfunction in two-kidney, one-clip renovascular hypertensive rats fed with a high-fat-sucrose diet (2K1C rats on HFS diet). Sesamin was intragastrically administered to 2K1C rats on HFS diet for eight weeks. Then, we measured the levels of serum hydrogen peroxide (H?O?), total antioxidant capability (T-AOC), renal malonaldehyde (MDA), total-erythrocuprein (T-SOD) and glutathione peroxidase (GSH-P(X)). The expressions of endothelial nitric oxide synthase (eNOS), nitrotyrosine and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p47(phox) in the left and right renal cortexes were detected by Western blotting. Pathological changes in the left and right renal cortexes were observed by periodic acid-schiff staining (PAS) and Masson's staining. Treatment with sesamin (120 and 60mg/kg?1·d?1) in 2K1C rats on HFS diet improved renal function, corrected structural abnormalities, and attenuated renal oxidative stress. Furthermore, sesamin increased eNOS protein expression and reduced nitrotyrosine and p47phox protein expression. These results demonstrated that long-term treatment with sesamin had renoprotective effect and improved renal endothelial dysfunction via upregulation of eNOS expression and reduction of NO oxidative inactivation in both clipped and contralateral kidneys of 2K1C rats on HFS diet, and sesamin may have a favorably therapeutic value in treating chronic kidney disease in patients with hypertension and hyperlipemia.     

Nitric oxide dynamics and endothelial dysfunction in type II model of genetic diabetes

Although diabetes is a major risk factor for vascular diseases, e.g., hypertension and atherosclerosis, mechanisms that underlie the "risky" aspects of diabetes remain obscure. The current study is intended to examine the notion that diabetic endothelial dysfunction stems from a heightened state of oxidative stress induced by an imbalance between vascular production and scavenging of reactive oxygen/nitrogen species. Goto-Kakizaki (GK) rats were used as a genetic animal model for non-obese type II diabetes. Nitric oxide (NO) bioavailability and O2- generation in aortic tissues of GK rats were assessed using the Griess reaction and a lucigenin-chemiluminescence-based technique, respectively. Organ chamber-based isometric tension studies revealed that aortas from GK rats had impaired relaxation responses to acetylcholine whereas a rightward shift in the dose-response curve was noticed in the endothelium-independent vasorelaxation exerted by the NO donor sodium nitroprusside. An enhancement in superoxide (O2-) production and a diminuation in NO bioavailability were evident in aortic tissues of GK diabetic rats. Immunoblotting and high-performance liquid chromatography (HPLC)-based techniques revealed, respectively, that the above inverse relationship between O2- and NO was associated with a marked increase in the protein expression of nitric oxide synthase (eNOS) and a decrease in the level of its cofactor tetrahydrobiopterin (BH4) in diabetic aortas. Endothelial denudation by rubbing or the addition of pharmacological inhibitors of eNOS (e.g. N(omega)-nitro-L-arginine methyl ester (L-NAME)), and NAD(P)H oxidase (e.g. diphenyleneiodonium, apocynin) strikingly reduced the diabetes-induced enhancement in vascular O2- production. Aortic contents of key markers of oxidative stress (isoprostane F2alpha III, protein-bound carbonyls, nitrosylated protein) in connection with the protein expression of superoxide generating enzyme NAD(P)H oxidase (e.g. p47phox, pg91phox), a major source of reactive oxygen species in vascular tissue, were elevated as a function of diabetes. In contrast, the process involves in the vascular inactivation of reactive oxygen species exemplified by the activity of CuZnSOD was reduced in this diseased state. Our studies suggest that diabetes produces a cascade of events involving production of reactive oxygen species from the NADPH oxidase leading to oxidation of BH4 and uncoupling of NOS. This promotes the oxidative inactivation of NO with subsequent formation of peroxynitrite. An alteration in the balance of these bioactive radicals in concert with a defect in the antioxidant defense counteracting mechanism may favor a heightened state of oxidative stress. This phenomenon could play a potentially important role in the pathogenesis of diabetic endothelial dysfunction.     

Insulin and metformin may prevent renal injury in young type 2 diabetic Goto-Kakizaki rats

Type 2 diabetes is increasing at epidemic proportions throughout the world, and diabetic nephropathy is the principal cause of end stage renal failure. Approximately 40% of patients with type 2 diabetes may progress to nephropathy and a good metabolic control can prevent the development of diabetic renal injury. The aim of our study was to evaluate, in young type 2 diabetic Goto-Kakizaki (GK) rats fed with atherogenic diet, the effects of the anti-diabetic compounds insulin, metformin and gliclazide on renal damage. GK rats fed with atherogenic diet showed increased body weight and fasting blood glucose, total cholesterol, triglycerides, C-reactive protein and protein carbonyl levels and lower HDL-cholesterol concentration; renal markers of inflammation and fibrosis were also elevated. All the anti-diabetic agents ameliorated fasting glycaemia and insulin resistance but only insulin and metformin were able to improve glycoxidation, fibrosis and inflammation kidney parameters. Our data suggest that insulin and metformin treatments, improving glicoxidative, inflammatory and fibrotic renal damage markers, play a key role in the prevention of diabetic nephropathy.     

Ameliorative effect of astaxanthin on endothelial dysfunction in streptozotocin-induced diabetes in male rats

The present study was designed to examine whether astaxanthin (ASX, 3,3-dihydroxybeta, beta-carotene-4,4-dione, CAS 472-61-7), a dietary antioxidant carotenoid that is naturally present in algae, crustaceans, and fish, has a protective effect on endothelial dysfunction of aortas in diabetic rats and the possible molecular mechanism involved. Male Wistar rats were randomly divided into four groups: control rats, diabetic rats, diabetic rats treated with ASX (10 mg/kg/d), and control rats treated with ASX. Type 1 diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/ kg). STZ-induced diabetes in rats was complicated with excessive oxidative stress and endothelial dysfunction, increased serum oxidized low-density lipoprotein (ox-LDL) and aortic malondialdehyde (MDA) levels, inhibited endothelium-dependent vasorelaxation to acetylcholine (ACh) and unaffected endothelium-dependent vasorelaxation to sodium nitroprusside (SNP). Simultaneously, lectin-like oxLDL receptor-i (LOX-1) expression was enhanced and endothelial nitric oxide (NO) synthase (eNOS) expression was reduced in the aortas of diabetic rats. ASX treatment could significantly decrease serum oxLDL and aortic MDA levels, attenuate blunted endothelium-dependent vasodilator responses to ACh, upregulate eNOS expression, and decrease LOX-1 expression. These results indicated that ASX could ameliorate diabetic endothelial dysfunction by inhibiting the ox-LDLLOX-1-eNOS pathway. Treatment with ASX might be clinically useful for diabetic complications associated with endothelial dysfunction.     

Resveratrol prevents endothelial nitric oxide synthase uncoupling and attenuates development of hypertension in spontaneously hypertensive rats

Endothelial dysfunction is a hallmark of hypertension and vascular oxidative stress can contribute to endothelial dysfunction and hypertension development. Resveratrol is an antioxidant polyphenol which improves endothelium dependent relaxation, the mechanisms of which are unknown. Also, the role of resveratrol in hypertension remains to be established. The purpose of this study was to investigate the mechanisms of resveratrol induced improvement of endothelial function and establish its role in hypertension. SHR and WKY rats, 3-4 weeks old, were treated with resveratrol in drinking water for 10 weeks, untreated SHR and WKY rats served as controls. At the end of the treatment, control SHR exhibited increased blood pressure, oxidative stress and attenuated endothelium dependent relaxation in comparison to WKY rats. The impaired endothelium function in SHR was associated with lower nitrite/nitrate levels, elevated nitrotyrosine content and eNOS uncoupling. Resveratrol treatment attenuated hypertension development in SHR as indicated by lower blood pressure in resveratrol treated SHR (SHR-R) compared to control SHR. SHR-R also exhibited reduced H(2)O(2) content and elevated superoxide dismutase activity. Resveratrol treatment normalized endothelium dependent vasorelaxation in SHR. In parallel, resveratrol restored nitrite/nitrate levels and normalized nitrotyrosine content in SHR. SHR exhibited increased l-arginine dependent superoxide production which was blocked by NOS inhibitor l-NNA, suggesting eNOS uncoupling. eNOS uncoupling was prevented by resveratrol treatment. In conclusion, early treatment with resveratrol lowers oxidative stress, preserves endothelial function and attenuates development of hypertension in SHR. More importantly, prevention of eNOS uncoupling and NO scavenging could represent novel mechanisms for resveratrol-mediated antihypertensive effects.     

Ameliorative effect of berberine on endothelial dysfunction in diabetic rats induced by high-fat diet and streptozotocin

Berberine can improve insulin resistance, lower blood glucose, and regulate lipid metabolism disorders which cause endothelial dysfunction, leading to vascular complications of type 2 diabetes mellitus. The aim of the present study was to investigate the effects of berberine on endothelial dysfunction of aortas in type 2 diabetes mellitus rats and its mechanism. Wistar rats were randomly divided into four groups: diabetic rats, control rats, diabetic rats treated with berberine (100 mg/kg), and control rats treated with berberine. The serum fasting blood glucose, insulin, total cholesterol, triglyceride and nitric oxide (NO) levels were tested. Acetylcholine-induced endothelium-dependent relaxation and sodium nitroprusside induced endothelium-independent relaxation were measured in aortas for estimating endothelial function. The expression of endothelial nitric oxide synthase (eNOS) mRNA was measured by RT-PCR, and the protein expressions of eNOS and NADPH oxidase (NOX4) were analyzed by western blot. The results showed that berberine significantly decreased fasting blood glucose, and triglyceride levels in diabetic rats. Berberine also improved endothelium-dependent vasorelaxation impaired in aorta. The expressions of eNOS mRNA and protein were significantly increased, while NOX4 protein expression was decreased in aortas from diabetic rats with berberine treatment. Moreover, serum NO levels were elevated after berberine treatment. In conclusion, berberine restores diabetic endothelial dysfunction through enhanced NO bioavailability by up-regulating eNOS expression and down-regulating expression of NADPH oxidase.     

自发性糖尿病GK 大鼠糖尿病周围神经病变模型的建立

摘要： 目的 通过高脂饲养 GK 大鼠建立一种符合人类糖尿病周围神经病变 （DPN） 发病特点, 又操作简单的 DPN 大鼠模型。方法 7~8 周龄 SPF 级雄性自发性 2 型糖尿病 GK 大鼠 30 只, 喂养高脂饲料造模。另取 30 只 SPF 级正常 Wistar 大鼠作为正常组, 喂养普通饲料。每周监测动物血糖、 体质量、 饮水量、 饲料量。分别于干预 8 周、 12 周、 16 周后检测血清糖化血红蛋白、 坐骨神经传导速度, 取对侧坐骨神经做 HE 染色, TUNEL 染色计算细胞凋亡指数。结果 随着造模时间延长, GK 大鼠逐渐出现多饮、 多食、 生长迟缓等表现。与正常组相比, 造模 12 周及 16 周的大鼠血糖、 糖化血红蛋白升高 （P < 0.01）, 感觉神经传导速度降低 （P < 0.01）, 运动神经传导速度有一定下降趋势（12 周 P < 0.05, 16 周 P > 0.05）, 坐骨神经病理形态及雪旺细胞凋亡情况均提示 DPN 的形成, 并与正常大鼠形成鲜明对照 （凋亡指数 P < 0.01）。结论 长期高脂饲料喂养的 GK 大鼠是 DPN 研究的良好模型, 12 周是较为成熟且经济的造模时间。     

嗜酸乳杆菌调节NO及其氧化介质对动脉粥样硬化模型大鼠的影响

目的 研究嗜酸乳杆菌对一氧化氮（NO）及其氧化介质表达的影响,探讨嗜酸乳杆菌抗动脉粥样硬化的机 制。方法 24只SPF级雄性大鼠随机分为正常饮食组、高脂饮食组和嗜酸乳杆菌组,每组8只。正常饮食组大鼠以 普通饲料喂养,高脂饮食组以高脂饲料+腹腔注射维生素D3+免疫损伤法+FeSO4喂养建立动脉粥样硬化模型,嗜酸 乳杆菌组大鼠在高脂饮食组的基础上,每天灌胃0.5 mL嗜酸乳杆菌菌液（1×109 CFU/mL）,实验第4、8、12周末称量动 物体质量。喂养 12 周后处死动物,检测血清氧化低密度脂蛋白（oxLDL）、NO、精氨酸、精氨酸酶、过氧亚硝基 （ONOO-）含量。分离大鼠主动脉血管,HE染色观察主动脉形态学变化,Real-time PCR检测eNOS、iNOS mRNA表达, Western blot 检测主动脉NF-κB p65亚基的表达。结果 （1）整个实验过程中,高脂饮食组和嗜酸乳杆菌组大鼠体质 量变化差异无统计学意义（P＞0.05）,但较正常饮食组均有明显增长（P < 0.01）。（2）HE染色结果显示,高脂饮食大鼠 中主动脉形成广泛的动脉粥样硬化病变,嗜酸乳杆菌组大鼠的主动脉形态得到明显改善,仅内皮细胞增生,没有观 察到平滑肌细胞的坏死。（3）与正常饮食组相比,高脂饮食组大鼠血清oxLDL、ONOO-、精氨酸酶、主动脉iNOS mRNA 和细胞核NF-κB p65表达水平升高（P＜0.01）,血清NO和精氨酸含量、主动脉eNOS mRNA 及胞质NF-κB p65亚基表 达水平降低（P＜0.01）;而嗜酸乳杆菌恰好能逆转上述改变（P＜0.01）。结论 嗜酸乳杆菌可能通过调节NOS的表 达、增加NO生物利用度、保护内皮功能来发挥抗动脉粥样硬化作用。     

8羟基脱氧鸟苷在2型糖尿病大鼠肾脏的表达及瑞舒伐他汀钙的影响

目的观察8-羟基脱氧鸟苷(8-OHdG)在2型糖尿病模型大鼠肾脏的表达及瑞舒伐他汀钙(Rosuvastatin)对它的影响。方法将大鼠分为正常对照组(C)、糖尿病组(D)、瑞舒伐他汀钙治疗组(N),比较各组大鼠肾组织中丙二醛(MDA)含量、超氧化物岐化酶(SOD)活性,和8羟基脱氧鸟苷(8-OHdG)含量,同时观察血糖、血胰岛素、肾功能和肾脏形态变化。结果与正常组比较,糖尿病组血液中MDA含量明显上升(P<0.05),SOD活性显著下降(P<0.05),8-OHdG增多(P<0.05),肾功能和肾脏形态受损,而瑞舒伐他汀钙治疗组的上述表达较糖尿病组明显改善。结论 8-OHdG在糖尿病肾病中的表达明显增加,而瑞舒伐他汀钙可以通过抑制氧化应激反应对2型糖尿病模型大鼠肾脏产生保护作用。     

Nitric oxide homeostasis as a target for drug additives to cardioplegia

The vascular endothelium of the coronary arteries has been identified as the important organ that locally regulates coronary perfusion and cardiac function by paracrine secretion of nitric oxide (NO) and vasoactive peptides. NO is constitutively produced in endothelial cells by endothelial nitric oxide synthase (eNOS). NO derived from this enzyme exerts important biological functions including vasodilatation, scavenging of superoxide and inhibition of platelet aggregation. Routine cardiac surgery or cardiologic interventions lead to a serious temporary or persistent disturbance in NO homeostasis. The clinical consequences are "endothelial dysfunction", leading to "myocardial dysfunction": no- or low-reflow phenomenon and temporary reduction of myocardial pump function. Uncoupling of eNOS (one electron transfer to molecular oxygen, the second substrate of eNOS) during ischemia-reperfusion due to diminished availability of L-arginine and/or tetrahydrobiopterin is even discussed as one major source of superoxide formation. Therefore maintenance of normal NO homeostasis seems to be an important factor protecting from ischemia/reperfusion (I/R) injury. Both, the clinical situations of cardioplegic arrest as well as hypothermic cardioplegic storage are followed by reperfusion. However, the presently used cardioplegic solutions to arrest and/or store the heart, thereby reducing myocardial oxygen consumption and metabolism, are designed to preserve myocytes mainly and not endothelial cells. This review will focus on possible drug additives to cardioplegia, which may help to maintain normal NO homeostasis after I/R.     

Malfunction of vascular control in lifestyle-related diseases: mechanisms underlying endothelial dysfunction in the insulin-resistant state

It is tempting to speculate that increased vasoconstriction and loss of endothelium-dependent vasodilation might be etiological factors of elevated blood pressure in the insulin-resistant state. Vascular contraction induced by angiotensin II and the expression of NAD(P)H oxidase were increased in the aorta of insulin-resistant mice. In addition, both angiotensin II type 1 receptor expression and superoxide anion production were up-regulated in these mice. Another mechanism for imparing endothelial function is the uncoupling of endothelial nitric oxide synthase (eNOS). It has become clear from studies on the aorta of insulin-resistant rat that insulin resistance may be a pathogenic factor for endothelial dysfunction through impaired eNOS activity and increased oxidative breakdown of NO (nitric oxide) due to an enhanced formation of superoxide anion (NO/superoxide anion imbalance), which are caused by relative deficiency of tetrahydrobiopterin, a cofactor of NOS, in vascular endothelial cells. Supplementation of tetrahydrobiopterin restored endothelial function and relieved oxidative tissue damage through activation of eNOS in those rats. These results indicate that generation of superoxide anion from NAD(P)H oxidases and an uncoupled eNOS may be pathogenic factors for impaired endothelial function and hypertension in the insulin-resistant state.     

Sesamin enhances nitric oxide bioactivity in aortas of spontaneously hypertensive rats

OBJECTIVE To explore the underlying mechanisms involved in the effect of sesamin on aortic NO bioactivity in spontaneously hypertensive rat(SHR).METHODS Sesamin was orally administered for consecutive 8 weeks in SHR.Systolic blood pressure(SBP)was measured using the tail-cuff method.The aortas were isolated and in vitro vascular reactivity studies were performed.Superoxide anion production in carotid arteries was assessed by dihydroethidium fluorescence staining.The protein expression of endothelial nitric oxide synthase(eNOS),phosphorylated eNOS(P-eNOS),dihydrofolate reductase(DHFR),nicotinamide adenine dinucleotide phosphate(NADPH)oxidase subunit p47 phox and copper,zinc-superoxide dismutase(Cu/Zn-SOD)in aortas was detected by Western blotting.The dimeric form of eNOS in aortas was determined by low-temperature SDS-PAGE.Aortic level of nitrotyrosine and activities of antioxidant enzymes,namely,total SOD(T-SOD),glutathione peroxidase(GPx)and catalase were also detected.RESULTS In SHR,sesamin treatment reduced SBP,improved vascular relaxation induced by acetylcholine and enhanced aortic NO bioactivity.Sesamin treatment enhanced NO biosynthesis in SHR aortas was due to upregulated P-eNOS and suppressed eNOS uncoupling,and the latter effect might be attributed to decreased nitrotyrosine and upregulated DHFR.Sesamin also reducd the NO oxidative inactivation and decreased the superoxide anion production through downregulation of p47 phox and amelioration of eNOS uncoupling.In addition,sesamin treatment did not alter the levels of GPx and catalase activity but obviously reduced the compensatory elevated T-SOD activity and Cu/Zn-SOD protein expression.CONCLUSION Chronic treatment with sesamin could reduce hypertension and improve endothelial dysfunction through enhancement of NO bioactivity in SHRs aortas.     

姜黄素类似物H8对糖尿病大鼠心脏的保护作用

目的 探讨姜黄素类似物H8对糖尿病大鼠心脏结构及功能的影响及机制。方法 采用随机数字表法将 24只雄性SD大鼠分为对照组、模型组和H8组,每组8只。模型组和H8组通过高脂高糖饮食诱导8周后腹腔注射链 脲佐菌素（STZ）建立2型糖尿病大鼠模型。H8组大鼠用H8（6 mg/kg）连续灌胃4周,对照组和模型组用等量羧甲基纤 维素钠连续灌胃4周。第4周末采用超声心动图评价各组大鼠心脏结构及功能变化。检测各组大鼠血液生化指标, 处死大鼠后检测心肌组织病理学改变,心肌组织中乳酸脱氢酶（LDH）、总超氧化物歧化酶（T-SOD）和丙二醛（MDA） 水平。结果 与对照组相比,模型组大鼠的左心室室壁运动减弱、心室重构明显、左室射血分数（LVEF）和短轴缩短 率（FS）降低,血糖、总胆固醇、三酰甘油水平明显升高,心肌细胞结构紊乱,心肌组织中LDH、MDA水平明显升高,T-SOD水平明显降低（P＜0.05）;与模型组相比,H8组大鼠左心室室壁运动增强、心室重构、LVEF和FS及心肌细胞排 列紊乱情况明显改善,血糖、总胆固醇、三酰甘油水平降低,心肌组织中LDH、MDA水平降低,T-SOD水平升高（P＜ 0.05）。结论 姜黄素类似物H8对糖尿病大鼠心肌损伤具有保护作用,其机制可能与抑制心室重构、改善心功能及 降低血糖、血脂及氧化应激因子水平有关。     

大豆异黄酮对2型糖尿病大鼠血清中SOD MDA GSH及NO的影响

目的研究大豆异黄酮对2型糖尿病大鼠血清中超氧化物歧化酶(SOD)、丙二醛(MDA)、还原型谷胱甘肽(GSH)及一氧化氮(NO)的影响。方法以高脂饲料喂养后的雄性SD大鼠腹腔注射小剂量链脲佐菌素(STZ)诱导2型糖尿病模型。将实验动物随机分为普食对照组、糖尿病对照组、大豆异黄酮250mg/kg、50mg/kg剂量干预组。检测各组喂养6周、10周的血糖水平,检测第10周后大鼠血清中SOD、MDA、GSH及NO的变化。结果与糖尿病对照组相比,大豆异黄酮250mg/kg剂量干预组大鼠血清中的SOD明显升高(P<0.05),MDA与NO明显下降(P<0.05);大豆异黄酮50mg/kg剂量干预组大鼠血清中GSH明显升高(P<0.05)。结论大豆异黄酮能改善2型糖尿病大鼠的抗氧化能力。     

2型糖尿病大鼠主动脉内皮细胞氧化损伤及缬沙坦的保护作用

目的探讨2型糖尿病大鼠氧化应激与主动脉内皮细胞损伤的关系,观察缬沙坦对两者的影响。方法SD大鼠,用长期高能量饮食加小剂量注射链脲佐菌素(STZ)的方法复制模型。注射STZ12wk末,将大鼠分为3组:正常组、糖尿病组、缬沙坦治疗组(24mg·kg-1·d-1,灌胃给药8wk)。在注射STZ12和20wk末,检测大鼠的内皮依赖性血管舒张反应及主动脉内皮形态,血清超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性,丙二醛(MDA)和一氧化氮(NO)含量,以及主动脉一氧化氮合酶(NOS)基因表达情况。结果①12wk末,糖尿病大鼠主动脉对低浓度乙酰胆碱(ACh)舒张反应减弱,局部内皮隆起,血清SOD、GSH-Px活性增强,MDA和NO含量增加,主动脉iNOS mRNA表达明显上调,eNOS mRNA表达无明显改变。②20wk末,糖尿病大鼠主动脉对各浓度ACh的反应性均减弱,主动脉内皮变性、坏死,血清SOD、GSH-Px活性减弱,MDA含量进一步增加,NO含量下降,主动脉iNOS mRNA表达仍升高,eNOS mRNA表达降低,缬沙坦治疗后能减轻主动脉病变,改善血清SOD、GSH-Px、MDA、NO及主动脉NOS mRNA表达的异常。结论糖尿病大鼠的氧化应激和NO系统的紊乱参与了主动脉病变过程,增强机体抗氧化能力及调节NO生成可能是缬沙坦发挥主动脉保护作用的机制之一。