Nutritional Prevention on Hypertension, Cerebral Hemodynamics and Thrombosis in Stroke-Prone Spontaneously Hypertensive Rats

1. Stroke-prone spontaneously hypertensive rats (SHRSP/Izm), which become severely hypertensive and exhibit a very high incidence of stroke (cerebral hemorrhage and/or infarction), are used widely for the study of the hypertension and stroke. In the previous study, we indicated that high thrombotic tendency of cerebral microvessels in SHRSP/Izm compared with stroke-resistant SHR (SHR/Izm) and normotensive Wistar Kyoto rats (WKY/Izm) at aged period. 2. L-arginine, a substrate of nitric oxide (NO), and voluntary exercise reduced blood pressure and thrombotic tendency in cerebral microvessels caused by highly production of NO in vivo. Furthermore, antioxidants show that the effects of antihypertensive and antithrombosis in SHRSP/Izm. 3. Although SHRSP/Izm become genetically hypertensive and exhibit stroke, a number of nutritional factors, particularly antioxydative nutrient, have preventive effects on hypertension, cerebral blood flow dysfunction, thrombus formation, and neuronal cell death in SHRSP/Izm. Our results indicate that those treatments are beneficial in the prevention of hypertension and stroke and that the nutritional science is very important for "prediction and prevention medicine."     

Diet‐induced Obesity Delays Cardiovascular Recovery from Stress in Spontaneously Hypertensive Rats

Objective: Blood pressure (BP) and heart rate (HR) responses to stress are significant predictors of cardiovascular morbidity and mortality. Because obesity is a major risk factor for cardiovascular disease, we examined whether diet‐induced obesity alters the BP and HR responses to stress and whether these alterations are associated with augmented cardiovascular morbidity in the rat. Research Methods and Procedures: Adult male spontaneously hypertensive rats were fed either a normal diet or high‐fat diet (HFD) for 12 weeks. At weeks 0 and 12, body weight was measured, and BP and HR were recorded by radiotelemetry throughout three consecutive day and night periods and in response to 30‐minute immobilization stress. At the end of the 12‐week intervention, the rats were sacrificed, and their organs and sera were collected. Results: With the intervention, HFD rats showed a significantly greater increase in body weight (as expected) and circulating leptin and free fatty acid levels compared with normal diet rats. In addition, they showed similar increases in BP and HR elevations during stress but significantly slower BP and HR decreases after stress. These HFD‐induced delays in stress recovery were associated with BP and HR elevations during the night (behaviorally active) period and with augmentations in cardiac mass. Discussion: The results of this study indicate that, in spontaneously hypertensive rats, dietary obesity delays cardiovascular recovery from stress, and, in parallel, it promotes the development of nocturnal hypertension as well as cardiac hypertrophy. This suggests that dietary obesity may significantly potentiate the impact of daily stressful experiences on the cardiovascular system.     

Effects of Metformin on Tissue Oxidative and Dicarbonyl Stress in Transgenic Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein

Inflammation and oxidative and dicarbonyl stress play important roles in the pathogenesis of type 2 diabetes. Metformin is the first-line drug of choice for the treatment of type 2 diabetes because it effectively suppresses gluconeogenesis in the liver. However, its “pleiotropic” effects remain controversial. In the current study, we tested the effects of metformin on inflammation, oxidative and dicarbonyl stress in an animal model of inflammation and metabolic syndrome, using spontaneously hypertensive rats that transgenically express human C-reactive protein (SHR-CRP). We treated 8-month-old male transgenic SHR-CRP rats with metformin (5 mg/kg/day) mixed as part of a standard diet for 4 weeks. A corresponding untreated control group of male transgenic SHR-CRP rats were fed a standard diet without metformin. In a similar fashion, we studied a group of nontransgenic SHR treated with metformin and an untreated group of nontransgenic SHR controls. In each group, we studied 6 animals. Parameters of glucose and lipid metabolism and oxidative and dicarbonyl stress were measured using standard methods. Gene expression profiles were determined using Affymetrix GeneChip Arrays. Statistical significance was evaluated by two-way ANOVA. In the SHR-CRP transgenic strain, we found that metformin treatment decreased circulating levels of inflammatory response marker IL-6, TNFα and MCP-1 while levels of human CRP remained unchanged. Metformin significantly reduced oxidative stress (levels of conjugated dienes and TBARS) and dicarbonyl stress (levels of methylglyoxal) in left ventricles, but not in kidneys. No significant effects of metformin on oxidative and dicarbonyl stress were observed in SHR controls. In addition, metformin treatment reduced adipose tissue lipolysis associated with human CRP. Possible molecular mechanisms of metformin action–studied by gene expression profiling in the liver–revealed deregulated genes from inflammatory and insulin signaling, AMP-activated protein kinase (AMPK) signaling and gluconeogenesis pathways. It can be concluded that in the presence of high levels of human CRP, metformin protects against inflammation and oxidative and dicarbonyl stress in the heart, but not in the kidney. Accordingly, these cardioprotective effects of metformin might be especially effective in diabetic patients with high levels of CRP.     

生姜提取物对阿尔茨海默病大鼠动物模型的氧化应激因子的影响

研究生姜提取物(Ginger Root Extract)对β淀粉样蛋白(β-amyloid protein,Aβ)所致阿尔茨海默病(Alzheirner’s disease,AD)大鼠脑组织氧化应激的影响,进一步探讨生姜提取物对AD的可能治疗作用及其机制。SD健康大鼠60只,雌雄各半,随机分成OP+LG组、OP+MG组、OP+HG组、SHAM组、OP+HupA组和OP组。药物干预4周后,以超氧化物歧化酶(SOD)、过氧化氢酶(CAT)免疫组化染色及丙二醛(MDA)Elisa分析比较大鼠大脑氧化应激指标及病理变化。结果显示OP+HG组、OP+HupA组的SOD、CAT的阳性表达活性明显升高(P<0.05),MDA水平下降显著(P<0.05);在OP+LG组、OP+MG组,干预效果不显著(P>0.05)。生姜提取物在高剂量时对阿尔茨海默病(AD)大鼠具有提高SOD、CAT阳性表达活性及降低MDA水平作用。     

Catecholamine Content Changes in Brain Regions of Spontaneously Hypertensive Rats Under Immobilization Stress

We compared the effect of immobilization stress on noradrenaline (NA) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) content in two brain regions--diencephalon and pons-medulla oblongata--in young and adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). In SHR, NA content decreased with time after the onset of the stress, whereas levels of its metabolite MHPG increased. In WKY, NA and MHPG showed no change. The MHPG/NA ratio in both regions increased relative to the duration of the stress in SHR, whereas it remained almost constant in WKY. The rate of increase in the ratio was much higher in the diencephalon of adult (12-week-old) than of young (4-week-old) SHR. In SHR, NA turnover in the brain is readily affected by environmental stress, and these changes in the noradrenergic system may induce or sustain hypertension.     

Time-Dependent Effects of Training on Cardiovascular Control in Spontaneously Hypertensive Rats: Role for Brain Oxidative Stress and Inflammation and Baroreflex Sensitivity

Baroreflex dysfunction, oxidative stress and inflammation, important hallmarks of hypertension, are attenuated by exercise training. In this study, we investigated the relationships and time-course changes of cardiovascular parameters, pro-inflammatory cytokines and pro-oxidant profiles within the hypothalamic paraventricular nucleus of the spontaneously hypertensive rats (SHR). Basal values and variability of arterial pressure and heart rate and baroreflex sensitivity were measured in trained (T, low-intensity treadmill training) and sedentary (S) SHR at weeks 0, 1, 2, 4 and 8. Paraventricular nucleus was used to determine reactive oxygen species (dihydroethidium oxidation products, HPLC), NADPH oxidase subunits and pro-inflammatory cytokines expression (Real time PCR), p38 MAPK and ERK1/2 expression (Western blotting), NF-κB content (electrophoretic mobility shift assay) and cytokines immunofluorescence. SHR-S vs. WKY-S (Wistar Kyoto rats as time control) showed increased mean arterial pressure (172±3 mmHg), pressure variability and heart rate (358±7 b/min), decreased baroreflex sensitivity and heart rate variability, increased p47^phox and reactive oxygen species production, elevated NF-κB activity and increased TNF-α and IL-6 expression within the paraventricular nucleus of hypothalamus. Two weeks of training reversed all hypothalamic changes, reduced ERK1/2 phosphorylation and normalized baroreflex sensitivity (4.04±0.31 vs. 2.31±0.19 b/min/mmHg in SHR-S). These responses were followed by increased vagal component of heart rate variability (1.9-fold) and resting bradycardia (−13%) at the 4th week, and, by reduced vasomotor component of pressure variability (−28%) and decreased mean arterial pressure (−7%) only at the 8th week of training. Our findings indicate that independent of the high pressure levels in SHR, training promptly restores baroreflex function by disrupting the positive feedback between high oxidative stress and increased pro-inflammatory cytokines secretion within the hypothalamic paraventricular nucleus. These early adaptive responses precede the occurrence of training-induced resting bradycardia and blood pressure fall.     

玉米蛋白及其水解产物对自发性高血压大鼠降血压作用的研究

目的探讨玉米蛋白及其水解产物对自发性高血压大鼠（SHR）血压的影响。方法 6～8周龄雄性SHR大鼠60只随机分为A组（玉米蛋白组）、B组（胃蛋白酶水解产物组）、C组（胰蛋白酶水解产物组）、D组（复合酶水解产物组）和E组（生理盐水对照组）,每组12只动物,均以1 g/kg体重剂量灌胃,测定灌胃0、1、2、4、6、8h后SHR血压值。结果胃蛋白酶水解产物、胰蛋白酶水解产物和复合酶水解产物在0～6 h内对SHR的血压升高具有明显抑制作用,其中0～2 h内降血压效果明显;各组水解产物中,以复合酶水解产物在0～6 h内降压效果最佳,SBP与生理盐水对照组、胃蛋白酶水解产物组和胰蛋白酶水解产物组相比具有极显著差异（P〈0.01）。结论玉米蛋白胃蛋白酶、胰蛋白酶和复合酶水解产物能有效地降低SHR大鼠的血压,为其在保健食品领域及医药方面的开发应用提供了参考。     

Prenatal Stress Causes Oxidative Damage to Mitochondrial DNA in Hippocampus of Offspring Rats

Mitochondrion, the primary source of reactive oxygen species (ROS), is also the target of ROS. 8-Hydroxy-2′-deoxyguanosine (8-OH-dG) is the major end-product of damaged DNA caused by ROS. In our previous studies, we showed that prenatal stress (PNS) preferentially caused cognitive dysfunction and increased ROS in the hippocampus of female offspring rats. The present study aimed to determine 8-OH-dG level of mitochondria in order to elucidate the mechanism of hippocampal pyramidal neuronal damage and cognitive dysfunction induced by PNS. Pregnant rats were divided into two groups: control group (undisturbed) and PNS group (exposed to a restraint stress for 7 days at the late stage of gestation). Offspring rats were divided into four groups: female-control group, male-control group, female-stress group, male-stress group and used at 30-day-old after their birth. The content of 8-OH-dG was determined by high performance liquid chromatography-electrochemical detection (HPLC-ECD). The results showed that the contents of 8-OH-dG in female and male prenatal stressed offspring were significantly higher than that in their respective controls (P < 0.001). 8-OH-dG level was significantly higher in the female-stress group than in the male-stress group (P < 0.05), whereas there was no any gender-dependent difference in the control groups. These results suggest that accumulation of oxidative mitochondrial DNA damage may play an important role in PNS-induced cognitive dysfunction in female offspring rats. Special issue article in honor of Dr. Akitane Mori.     

Role of the Renin-Angiotensin System,Renal Sympathetic Nerve System,and Oxidative Stress in Chronic Foot Shock-Induced Hypertension in Rats

Objective: The renin-angiotensin system (RAS) and renal sympathetic nerve system (RSNS) are involved in the development of hypertension. The present study is designed to explore the possible roles of the RAS and the RSNS in foot shock-induced hypertension.Methods: Male Sprague-Dawley rats were divided into six groups: control, foot shock, RSNS denervation, denervation plus foot shock, Captopril (angiotensin I converting enzyme inhibitor, ACE inhibitor) plus foot shock, and Tempol (superoxide dismutase mimetic) plus foot shock. Rats received foot shock for 14 days. We measured the quantity of thiobarbituric acid reactive substances (TBARS), corticosterone, renin, and angiotensin II (Ang II) in plasma, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and renal noradrenaline content. RAS component mRNA and protein levels were quantified in the cerebral cortex and hypothalamus.Results: The two week foot shock treatment significantly increased systolic blood pressure, which was accompanied by an increase in angiotensinogen, renin, ACE1, and AT1a mRNA and protein expression in the cerebral cortex and hypothalamus, an increase of the plasma concentrations of renin, Ang II, corticosterone, and TBARS, as well as a decrease in plasma SOD and GSH-Px activities. Systolic blood pressure increase was suppressed by denervation of the RSNS or treatment with Captopril or Tempol. Interestingly, denervation or Tempol treatment both decreased main RAS components not only in the circulatory system, but also in the central nervous system. In addition, decreased antioxidant levels and increased TBARS and corticosterone levels were also partially restored by denervation or treatment with Tempol or Captopril.Conclusions: RAS, RSNS and oxidative stress reciprocally potentiate to play important roles in the development of foot shock-induced hypertension.     

尾部悬吊对大鼠胸主动脉氧化应激水平的影响

目的:观察模拟失重对大鼠胸主动脉氧化应激水平的影响,探讨其可能机制。方法:采用3周尾部悬吊大鼠模型模拟失重状态,通过DHE荧光探针技术观察大鼠动脉血管超氧阴离子水平变化,通过比色法测定大鼠动脉血管丙二醛(MDA)含量,通过蛋白印记技术观察悬吊(SUS)大鼠和正常对照(CON)大鼠动脉血管NOX4、p22phox的表达变化。结果:尾部悬吊3周后,SUS组大鼠胸主动脉超氧阴离子水平较CON组明显增高,SUS组(0.849±0.023 nmol/mg protein)大鼠MDA含量较CON组(0.575±0.054nmol/mg protein)明显增加;SUS组大鼠胸主动脉的p22phox及NOX4蛋白表达均较CON组明显增强。结论:模拟失重3周可使大鼠胸主动脉氧化应激水平明显增高,p22phox及NOX4蛋白表达明显增多,结果提示,尾部悬吊模拟失重状态下氧化应激水平增高可能与NADPH氧化酶表达增高有关。     

Vasodilating Effect of Di-Peptides in Thoracic Aortas from Spontaneously Hypertensive Rats

In this study, we found that antihypertensive di-peptide Val-Tyr (VY) showed a vascular relaxation effect in KCl-induced contraction of thoracic aorta rings from 18-week-old spontaneously hypertensive rats among di-peptides of VY, Ile-Tyr, and Tyr-Val irrespective of their angiotensin I-converting enzyme inhibitory activity. The effect was endothelium-independent, and was closely associated with vascular responses in the vascular smooth muscle layer.     

EPO对肾脏缺血再灌注损伤大鼠肺内氧化应激状态的影响

目的:探讨促红细胞生成素(erythropoietin,EPO)对大鼠肾脏再灌注损伤模型肺内氧化应激状态的影响。方法:清洁级Sprague-Dawly(SD)大鼠36只适应性喂养1周后,随机分为3组,即假手术组(A组)、肾脏再灌注损伤组(B组)和EPO预处理组(C组),每组12只。A组大鼠只打开腹腔,游离双侧肾蒂但不夹闭;B组与C组都建立了大鼠肾脏再灌注损伤模型,且C组在夹闭肾蒂前2 h腹腔注射人重组EPO(5000 U/kg)。术后24 h,处死大鼠,检测肺内氧化应激水平。结果:A组大鼠精神状态良好,肾小管结构正常,未见明显上皮细胞肿胀、脱落,肺泡结构基本完整,肺泡间隔未增厚,有少量炎性细胞浸润;B组鼠毛耸立,无光泽,饮水量减少,肾小管结构破坏消失,肾小管扩张,可见大量蛋白管型,肺泡结构破坏,肺泡腔缩窄,肺泡间隔增厚,组织水肿,大量炎性细胞浸润;C组大鼠精神状态有所恢复,一般状况尚可,肾小管损伤较B组轻似,肾小管坏死区域有所减少,坏死偶见,肺泡壁轻度破坏,结构较为清晰,可见少量炎性细胞浸润。B组与C组大鼠的血尿素氮(blood urea nitrogen, BUN)与血肌酐(serum creatinine,Scr)水平、肺组织血红素氧合酶(heme oxygenase, HO)-1与丙二醛(malondialdehyde, MDA)水平都显著高于A组,C组以上指标均显著低于B组(P0.05)。B组超氧化物歧化酶(superoxide dismutase, SOD)和谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)的水平均显著高于A组(均P0.05),而C组SOD和GSH-Px的水平均显著高于B组(均P0.05),A组与C组间对比无显著差异。结论:EPO用于大鼠肾脏再灌注损伤模型能缓解肺内氧化应激状态,促进肾功能及肺组织恢复,发挥肾脏保护作用。     

Malathion-induced Oxidative Stress in Rat Brain Regions

Malathion is a pesticide with high potential for human exposure. However, it is possible that during the malathion metabolism, there is generation of reactive oxygen species (ROS) and malathion may produce oxidative stress in intoxicated rats. The present study was therefore undertaken to determine malathion-induced lipid peroxidation (LPO), protein carbonylation and to determine whether malathion intoxication alters the antioxidant system in brain rats. Malathion was administered intraperitoneally in the acute and chronic protocols in the doses of 25, 50, 100 and 150 mg malathion/kg. The results showed that LPO in brain increased in both protocols. The increased oxidative stress resulted in an increased in the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), observed in cortex, striatum in the acute malathion protocol and hippocampus in the chronic malathion protocol. Our results demonstrated that malathion induced oxidative stress and modulated SOD and CAT activity in selective brain regions.     

Identification of Stim1 as a Candidate Gene for Exaggerated Sympathetic Response to Stress in the Stroke-Prone Spontaneously Hypertensive Rat

The stroke-prone spontaneously hypertensive rat (SHRSP) is known to have exaggerated sympathetic nerve activity to various types of stress, which might contribute to the pathogenesis of severe hypertension and stroke observed in this strain. Previously, by using a congenic strain (called SPwch1.72) constructed between SHRSP and the normotensive Wistar-Kyoto rat (WKY), we showed that a 1.8-Mbp fragment on chromosome 1 (Chr1) of SHRSP harbored the responsible gene(s) for the exaggerated sympathetic response to stress. To further narrow down the candidate region, in this study, another congenic strain (SPwch1.71) harboring a smaller fragment on Chr1 including two functional candidate genes, Phox2a and Ship2, was generated. Sympathetic response to cold and restraint stress was compared among SHRSP, SPwch1.71, SPwch1.72 and WKY by three different methods (urinary norepinephrine excretion, blood pressure measurement by the telemetry system and the power spectral analysis on heart rate variability). The results indicated that the response in SPwch1.71 did not significantly differ from that in SHRSP, excluding Phox2a and Ship2 from the candidate genes. As the stress response in SPwch1.72 was significantly less than that in SHRSP, it was concluded that the 1.2-Mbp congenic region covered by SPwch1.72 (and not by SPwch1.71) was responsible for the sympathetic stress response. The sequence analysis of 12 potential candidate genes in this region in WKY/Izm and SHRSP/Izm identified a nonsense mutation in the stromal interaction molecule 1 (Stim1) gene of SHRSP/Izm which was shared among 4 substrains of SHRSP. A western blot analysis confirmed a truncated form of STIM1 in SHRSP/Izm. In addition, the analysis revealed that the protein level of STIM1 in the brainstem of SHRSP/Izm was significantly lower when compared with WKY/Izm. Our results suggested that Stim1 is a strong candidate gene responsible for the exaggerated sympathetic response to stress in SHRSP.     

Antihypertensive Effects of Acetic Acid and Vinegar on Spontaneously Hypertensive Rats

To clarify the possibility of a preventive effect of dietary vinegar on blood pressure, long-term administration of vinegar or the acetic acid to SHR was examined. As a result, it was observed that acetic acid itself, the main component of vinegar, significantly reduced both blood pressure (p<0.05) and renin activity (p<0.01) compared to controls given no acetic acid or vinegar, as well as vinegar. There were no significant differences in angiotensin I-converting enzyme activity in various organs. As for the mechanism of this function, it was suggested that this reduction in blood pressure may be caused by the significant reduction in renin activity and the subsequent decrease in angiotensin II. From this study, it was also suggested that the antihypertensive effect of vinegar is mainly due to the acetic acid in it.     

拟南芥GLP13基因在植物抗氧化胁迫响应中的作用

类萌发素蛋白（germin-like protein, GLPs）是一类与小麦萌发素序列相似性较高、位于胞外基质的可溶性糖蛋白, 在植物的生长发育阶段以及对生物和非生物胁迫的应答中起着重要的作用。为了研究GLP13基因的生理功能, 我们分离并鉴定了GLP13的敲减突变体glp13, 同时构建了其超表达植株35S：：GLP13。用甲基紫精（methyl viologen, MV）处理2种不同基因型和野生型（WT）植株, 结果发现, 与野生型相比, 突变体glp13子叶变绿率较低, 主根生长受抑制较明显; 而超表达植株35S：：GLP13子叶变绿率较高, 主根生长的受抑制程度较WT轻。用MV处理2周的35S：：GLP13植株, 其叶绿素荧光参数Fv/Fm 的下降较野生型对照缓慢。半定量RT-PCR分析结果表明, 与野生型相比, 经MV处理4小时后的35S：：GLP13中抗氧化酶系基因FSD1的表达上调, 而CAT1、CSD1和UGT71C1的表达水平在35S：：GLP13、glp13和野生型植株三者之间没有明显差异。以上结果表明GLP13基因在拟南芥抗氧化胁迫响应中起重要作用。     

A Study on the Safety and Effects of Amorpha fruticosa Fruit Extract on Spontaneously Hypertensive Rats with Induced Type 2 Diabetes

Metabolic syndrome is characterized by a variety of diagnostic criteria: obesity, dyslipidemia, type 2 diabetes, and arterial hypertension. They contribute to the elevated risk of cardiovascular morbidity and mortality. The potential for Amorpha fruticosa L. (Fabaceae) to improve diabetes and metabolic disease is promising, based on in vitro tests. This is why a further investigation of the species is needed. Additionally, a toxicity review in relation to safety revealed that to date, there are no published data regarding the toxicity of A. fruticosa towards humans. This species could provide abundant and cheap resources because it is an aggressive invasive plant that grows almost unrestrictedly. The objective of this study was to evaluate the acute toxicity of a purified extract of A. fruticosa (EAF), and to assess its antioxidant, antihypertensive, and antihyperglycemic activity in streptozotocin-induced diabetic spontaneously hypertensive rats (SHRs). The EAF was slightly toxic (LD₅₀ = 2121 mg/kg, b.w.) when administered orally, and moderately toxic (LD₅₀ = 316 mg/kg, b.w.) at intraperitoneal administration, both in mice. The oral administration of EAF (100 mg/kg) for 35 days to SHRs caused significant decreases in the systolic pressure, blood glucose levels, and MDA quantity. It also increased the hepatic level of the endogenous antioxidant GSH, not only in diabetic SHRs, but also in the control group. An additional potential benefit to human health might be conferred through the environmental management of A. fruticosa based on its large-scale use for medicinal purposes, as this aggressive invasive species brings problems to natural habitats in many European countries.     

茶多酚对NASH 大鼠肝脏组织VEGF 及氧化应激的影响

目的:茶多酚对NASH大鼠肝脏组织VEGF及氧化应激的影响。方法:雄性SD大鼠30只,随机分为3组,正常对照组、模型组、茶多酚治疗组。正常组普通饲料喂养,模型组喂高脂饮食,茶多酚治疗组在高脂饮食12周后茶多酚(150mg(/kg.d)灌胃治疗,16周末处死各组大鼠,留取肝脏组织,观察各组大鼠肝组织病理改变,测定其肝脏丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性以及血管内皮生长因子(VEGF)、Ⅰ、Ⅲ型胶原的表达。结果:模型组大鼠肝组织中SOD活性降低而MDA含量以及VEGF、Ⅰ、Ⅲ型胶原表达均明显高于正常组。茶多酚治疗可减轻肝纤维化程度,显著升高肝组织中SOD活性、降低MDA含量以及VEGF、Ⅰ、Ⅲ型胶原表达水平。结论:茶多酚可通过抑制肝纤维化组织VEGF表达,降低肝组织氧化应激水平而发挥抗肝纤维化作用。     

Beneficial Effects of Simulated Gastro-Intestinal Digests of Fried Egg and Its Fractions on Blood Pressure,Plasma Lipids and Oxidative Stress in Spontaneously Hypertensive Rats

Background

We have previously characterized several antihypertensive peptides in simulated digests of cooked eggs and showed blood pressure lowering property of fried whole egg digest. However, the long-term effects of this hydrolysate and its fractions on blood pressure are not known. Therefore, the objectives of the study were to determine the effects of long term administration of fried whole egg hydrolysate and its fractions (i.e. egg white and egg yolk) on regulation of blood pressure and associated factors in cardiovascular disease such as plasma lipid profile and tissue oxidative stress.

Methods and Results

We used spontaneously hypertensive rats (SHR), an animal model of essential hypertension. Hydrolysates of fried egg and its fractions were prepared by simulated gastro-intestinal digestion with pepsin and pancreatin. 16–17 week old male SHRs were orally administered fried whole egg hydrolysate, non-hydrolyzed fried whole egg, egg white hydrolysate or egg yolk hydrolysates (either defatted, or not) daily for 18 days. Blood pressure (BP) and heart rate were monitored by telemetry. Animals were sacrificed at the end of the treatment for vascular function studies and evaluating plasma lipid profile and tissue oxidative stress. BP was reduced by feeding fried whole egg hydrolysate but not by the non-hydrolyzed product suggesting a critical role for in vitro digestion in releasing anti-hypertensive peptides. Egg white hydrolysate and defatted egg yolk hydrolysate (but not egg yolk hydrolysate) also had similar effects. Reduction in BP was accompanied by the restoration of nitric oxide (NO) dependent vasorelaxation and reduction of plasma angiotensin II. Fried whole egg hydrolysate also reduced plasma levels of triglyceride although it was increased by the non-hydrolyzed sample. Additionally the hydrolyzed preparations attenuated tissue oxidative stress.

Conclusion

Our results demonstrate that fried egg hydrolysates exert anti-hypertensive effects, improve plasma lipid profile and attenuate tissue oxidative stress in vivo.