Effect of Vitamin E on Blood-Brain Barrier Permeability in Aged Rats with PTZ-Induced Convulsions

The effect of vitamin E on blood-brain barrier (BBB) permeability was studied under conditions of pentylenetetrazole (PTZ)-induced convulsions in aged (23- to 24-month-old) male albino rats; Evans Blue was used as a tracer. The BBB permeability was found to increase considerably in rats with PTZ-evoked seizures; the Evans Blue contents in the left and right hemispheres and cerebellum + brainstem region were significantly higher than those in the control. Vitamin E at a dose of 70 mg/kg exerted practically no beneficial effect on the increased BBB permeability in rats with seizures, while a greater dose of vitamin E (700 mg/kg) exerted a significant protective effect, especially with respect to the cerebellum + brainstem regions (P < 0.01). The seizure-related rise in the arterial blood pressure was also smaller in the latter experimental group. Thus, our observations confirm the importance of the vitamin E dose as a protective factor for BBB permeability and demonstrate that the dose dependence of this antioxidant in aged animals differs from that in younger organisms.     

不同剂量甲泼尼龙对大鼠急性百草枯中毒肾脏的影响

目的：观察不同剂量甲泼尼龙治疗大鼠百草枯中毒肾脏损伤的疗效。方法：将120只Wistar大鼠随机分为五组,空白组,染毒组和干预组（根据甲泼尼龙剂量不同分为三组）,除空白组外,均予百草枯（22mg／kg）稀释后腹腔注射,2h后依照组别、体重注射甲泼尼龙,在第1、3、7天共3个时间点,按抽签法处死实验对象6只获取标本,观察肾功能和病理变化。结果：各组血尿素氮（P=0．001〈0．05）和肌酐（P=0．01〈0．05）差异有统计学意义,干预组中5mg／kg甲泼尼龙组同染毒组比较差异有统计学意义。不同时间点血尿素氮（P=0．007〈0．05）和肌酐（P=0．016〈0．05）差异有统计学意义,其中第七天明显低于第一、三天。病理评分各组（P=O．21〉0．05）差异无统计学意义。讨论：早期应用糖皮质激素治疗PQ中毒大鼠,可以显著减轻PQ中毒所致的肾损伤程度,改善肾功能,尤其小剂量改善显著,传统的大剂量糖皮质激素冲击治疗不值的推崇。     

不同剂量甲泼尼龙对大鼠急性百草枯中毒肾脏的影响

目的:观察不同剂量甲泼尼龙治疗大鼠百草枯中毒肾脏损伤的疗效。方法:将120只Wistar大鼠随机分为五组,空白组,染毒组和干预组(根据甲泼尼龙剂量不同分为三组),除空白组外,均予百草枯(22mg/kg)稀释后腹腔注射,2h后依照组别、体重注射甲泼尼龙,在第1、3、7天共3个时间点,按抽签法处死实验对象6只获取标本,观察肾功能和病理变化。结果:各组血尿素氮(P=0.001<0.05)和肌酐(P=0.01<0.05)差异有统计学意义,干预组中5mg/kg甲泼尼龙组同染毒组比较差异有统计学意义。不同时间点血尿素氮(P=0.007<0.05)和肌酐(P=0.016<0.05)差异有统计学意义,其中第七天明显低于第一、三天。病理评分各组(P=0.21>0.05)差异无统计学意义。讨论:早期应用糖皮质激素治疗PQ中毒大鼠,可以显著减轻PQ中毒所致的肾损伤程度,改善肾功能,尤其小剂量改善显著,传统的大剂量糖皮质激素冲击治疗不值的推崇。     

Effect of Sodium Selenite and Vitamin E on the Renal Cortex in Rats: An Ultrastructure Study

This study examined the use of vitamin E to alleviate toxic effects of sodium selenite. Adult male albino rats (n = 50) was divided into five groups. Group 1 was control, Groups 2 and 4 were treated with sodium selenite (2 mg/kg) for 2 and 4 weeks, respectively, Groups 3 and 5 were treated with sodium selenite (2 mg/kg) and vitamin E (100 mg/kg) for 2 and 4 weeks, respectively. Renal tissues were studied using anti-BCL2 and examined ultrastructurally. Positive Bax immunoreactivity was detected after 2 and more positive after 4 weeks and nearly all groups improved with co-administration of vitamin E. Ultrastructural study revealed lesions in Bowman's capsule and proximal convoluted tubules. The submicroscopic study revealed damage and necrosis of cortical structures after 2 and 4 weeks, respectively. After 4 weeks, cellular changes were seen, such as vacuolation and moderate degeneration of cells, widening of the urinary space scattered through the cortex with loss of cellular details, formation of apical buds, degeneration, and cellular rupture. Present findings disclosed an ameliorative effect of adding vitamin E to sodium selenite-induced changes in cortical tissues. Clinically, it is advised to add vitamin E to avoid selenium overdose hazards.     

CircITGA7对缺血性心律失常大鼠心肌细胞凋亡的影响

研究环状RNA ITGA7(circITGA7)在心律失常大鼠心肌细胞中的表达,并探讨其对心律失常大鼠心肌细胞凋亡的影响及机制。40只SPF级SD雄性大鼠,分为4组,分别为假手术组、心律失常组、circITGA7干扰心律失常组和对照干扰心律失常组,尾静脉注射circITGA7干扰腺相关病毒构建circITGA7干扰大鼠模型,并通过手术结扎冠状动脉前降支建立缺血性心律失常大鼠模型。通过荧光定量PCR法(Q-PCR)检测circITGA7在心律失常大鼠心肌组织中的表达水平。分别检测circITGA7对心律失常大鼠心肌氧化应激和凋亡的影响;Western blotting检测circITGA7对心律失常大鼠心肌细胞p-AKT和ITGA7蛋白表达的影响。Q-PCR结果显示circITGA7在心律失常大鼠心肌组织中的表达显着高于假手术组大鼠;与对照干扰心律失常组比较,circITGA7干扰心律失常组大鼠心律失常评分显著降低,差异具有统计学意义(p<0.01)。与假手术组比较,心律失常组大鼠心肌细胞SOD活力显著降低,MDA含量显著升高;与对照干扰心律失常组比较,circITGA7干扰心律失常组大鼠心律失常组大鼠心肌细胞SOD活力显著升高,MDA含量显著降低,差异具有统计学意义(p<0.01)。TUNEL检测结果显示,与假手术组比较,心律失常大鼠心肌细胞凋亡程度显著升高;与对照干扰心律失常组大鼠比较,circITGA7干扰心律失常组大鼠心肌细胞凋亡率为显著降低(p<0.01);Western blotting结果显示,与假手术组比较,心律失常大鼠心肌细胞p-AKT和ITGA7的蛋白表达水平均显著升高;与对照干扰心律失常组比较,circITGA7干扰心律失常组大鼠心肌细胞p-AKT和ITGA7的蛋白表达水平均显著下降(p<0.01)。干扰circITGA7能够抑制AKT路径,抑制心律失常大鼠心肌细胞氧化应激和细胞凋亡,缓解大鼠心律失常。     

Caspase-12抑制剂对百草枯中毒大鼠肝损伤的保护作用

目的:观察caspase-12抑制剂Z-ATAD-FMK对百草枯染毒大鼠肝脏caspase-12蛋白表达和肝细胞凋亡的影响,以及通过血清SOD和MDA的检测,探讨其对百草枯中毒大鼠肝脏保护作用和对机体氧化应激反应的作用。方法:50只健康Wistar大鼠随机分三组:A组为正常对照组;B组为模型组(PQ染毒);C组抑制剂组(PQ/Z-ATAD-FMK),于3d、7d处死B组和C组各10只大鼠。取血检测ALT、TBIL、SOD和MDA;HE染色观察肝组织病理学变化;免疫组化法检测caspase-12蛋白;二苯胺法检测细胞凋亡率。SPSS18.0统计分析。结果:Z-ATAD-FMK抑制剂组ALT、TBIL、MDA值低于模型组(P0.05),SOD高于模型组(P0.05);caspase-12蛋白表达和细胞凋亡率亦低于模型组(P0.05);HE染色显示凋亡和坏死程度也较模型组轻。结论:Caspase-12抑制剂Z-ATAD-FMK能减少百草枯中毒大鼠肝脏caspase-12蛋白表达和肝细胞凋亡率,减轻肝细胞坏死,对肝脏具有保护作用,同时可以抑制百草枯中毒大鼠的氧化应激反应。     

Effect of High Doses of Dietary Vitamin E on the Concentrations of Vitamin E in Several Brain Regions, Plasma, Liver, and Adipose Tissue of Rats

The object of this study was to assess the influence of high levels of dietary vitamin E on vitamin E concentrations in specific areas of the brain. Four-week-old male rats were fed vitamin E-deficient, control, and high-vitamin E (1,000 IU/kg) diets for 4 months. Concentrations of alpha-tocopherol in serum, adipose tissue, liver, cerebrum, cerebellum, and striatum were determined by liquid chromatography with fluorescence detection. In the high-vitamin E group, alpha-tocopherol concentrations in cerebrum, cerebellum, and striatum increased uniformly to 1.4-fold of values in controls; serum, adipose tissue, and liver attained even higher concentrations: 2.2-, 2.2-, and 4.6-fold, respectively, of control values. As observed before, brain levels of alpha-tocopherol were somewhat resistant to vitamin E deficiency, in contrast to the peripheral tissues.     

维生素E对三氯乙烯急性染毒大鼠肝脏脂质过氧化与抗氧化酶的影响

本文观察了用抗氧化剂维生素E预处理后,三氯乙烯(3000mg/kg B-W-) 一次性经口染毒24h 大鼠肝脏的超氧化物歧化酶、谷胱甘肽过氧化物酶等抗氧化酶活力及丙二醛含量的变化,结果表明三氯乙烯染毒组肝脏中丙二醛含量、超氧化物歧化酶活力及血清谷丙转氨酶、谷草转氨酶活力均高于对照组(P< 0-01) ;而维生素E干预组的丙二醛含量、超氧化物歧化酶活力及血清谷丙转氨酶、谷草转氨酶活力均分别低于三氯乙烯染毒组(P< 0-01) ,说明三氯乙烯急性染毒可引起肝脏脂质过氧化反应及肝损害,肝脏超氧化物歧化酶活力升高可能是机体受自由基及脂质过氧化反应刺激而诱导产生的一种适应性反应,维生素E对三氯乙烯所致的肝损害有一定的保护作用。     

维生素E 对癫痫大鼠认知功能障碍的治疗作用及其可能机制

目的:探讨维生素E(VitE)对癫痫大鼠认知功能障碍的治疗作用及其可能机制。方法:将30只成年雄性SD大鼠随机分为健康对照组、单纯致痫组(SE组)、VitE[按体重100mg/(kg.d)]干预组(VitE组)。采用Morris水迷宫实验方法检测致癫后大鼠学习记忆功能变化,同时检测脑组织匀浆中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、谷胱甘肽(GSH)、丙二醛(MDA)的水平。结果:(1)SE组大鼠寻找平台的潜伏期明显长于对照组,具有统计学意义(P<0.05),VitE组寻找平台的潜伏期相对于SE组显著缩短(P<0.05)。撤离平台后,SE组大鼠在平台所在象限的停留时间明显短于对照组(P<0.05),VitE治疗后大鼠在平台所在象限的停留时间较SE组显著延长(P<0.05)。(2)SE组SOD、GSH-PX、GSH显著下降,MDA明显增高,VitE干预组SOD、GSH-PX、GSH显著增高,而MDA明显下降,具有统计学意义(P<0.05)。结论:VitE可改善癫痫持续状态后大鼠认知功能,其可能机制是通过减轻海马区的氧化应激反应减轻海马区的损伤,从而实现改善认知功能。     

维生素E对癫痫大鼠认知功能障碍的治疗作用及其可能机制

目的：探讨维生素E（VitE）对癫痫大鼠认知功能障碍的治疗作用及其可能机制。方法：将30只成年雄性SD大鼠随机分为健康对照组、单纯致痫组（SE组）、VitE[按体重100mg／（kg·d）]干预组（VitE组）。采用Morris水迷宫实验方法检测致癫后大鼠学习记忆功能变化,同时检测脑组织匀浆中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH—PX）、谷胱甘肽（GSH）、丙二醛（MDA）的水平。结果：（1）SE组大鼠寻找平台的潜伏期明显长于对照组,具有统计学意义（P〈0．05）,VitE组寻找平台的潜伏期相对于SE组显著缩短（P〈0．05）。撤离平台后,SE组大鼠在平台所在象限的停留时间明显短于对照组（P〈0．05）,VitE治疗后大鼠在平台所在象限的停留时间较SE组显著延长（P〈0．05）。（2）SE组SOD、GSH—PX、GSH显著下降,MDA明显增高,VitE干预组SOD、GSH．PX-GSH显著增高,而MDA明显下降,具有统计学意义（P〈0．05）。结论：VitE可改善癫痫持续状态后大鼠认知功能,其可能机制是通过减轻海马区的氧化应激反应减轻海马区的损伤,从而实现改善认知功能。     

含氢HTK液对大鼠供心保存中心肌细胞凋亡的影响

目的:研究合氢HTK液对供心保存过程中心肌细胞凋亡的影响.方法:SD大鼠随机分4组:对照组(保存液为HTK液)、H1组(保存液为含氢浓度约0.8mM的HTK液),H2组(含氢浓度约0.4mM的HTK液),H3组(含氢浓度约0.2mM的HTK液).采用Langendorff离体大鼠心脏灌注法,心脏分别在各组保存液中冷保存(4℃)6h,Tunel染色测定心肌细胞凋亡率,荧光定量实时PCR检测凋亡相关基因Bcl-2和Bax的mRNA表达,分光光度法检测心肌组织中Caspase-3活性.结果:供心冷保存(4℃)6h后,H1、H2、H3组凋亡指数明显低于对照组.H1、H2、H3组的Bcl-2mRNA表达水平显著高于对照组(P<0.01或P<0.05);对照组的Bax mRNA水平明显高于H1、H2、H3组(P<0.01或P<0.05),对照组caspase-3活性明显高于H1、H2、H3组(P<0.01).结论:舍氢HTK明显抑制供心保存时大鼠心脏心肌细胞凋亡.     

Dietary Vitamin E Deficiency Increases Anxiety-Like Behavior in Juvenile and Adult Rats

Vitamin E deficiency from birth or infancy has recently been found to increase anxiety-like behavior in rodents. The present study was undertaken to elucidate the effect of dietary vitamin E deficiency on anxiety in adult rats in comparison with juvenile rats. Male Wistar rats, 3 or 10 weeks old, were divided into two groups and fed a control or vitamin E-deficient diet for 4 weeks. The results of behavioral analysis revealed that vitamin E-deficiency increased anxiety in both juvenile and adult rats. Plasma, liver, and brain α-tocopherol concentrations decreased significantly due to vitamin E deficiency in both age groups. Plasma corticosterone concentrations were higher in the vitamin E-deficient rats in response to the stress of a behavioral test. Based on these results, we conclude that dietary vitamin-E deficiency induces anxiety in adult rats as well as juvenile rats. This might be due to an elevated plasma corticosterone concentration.     

Ursodeoxycholic Acid Ameliorates Fructose-Induced Metabolic Syndrome in Rats

The metabolic syndrome (MS) is characterized by insulin resistance, dyslipidemia and hypertension. It is associated with increased risk of cardiovascular diseases and type-2 diabetes. Consumption of fructose is linked to increased prevalence of MS. Ursodeoxycholic acid (UDCA) is a steroid bile acid with antioxidant, anti-inflammatory activities and has been shown to improve insulin resistance. The current study aims to investigate the effect of UDCA (150 mg/kg) on MS induced in rats by fructose administration (10%) in drinking water for 12 weeks. The effects of UDCA were compared to fenofibrate (100 mg/kg), an agonist of PPAR-α receptors. Treatment with UDCA or fenofibrate started from the 6^th week after fructose administration once daily. Fructose administration resulted in significant increase in body weight, elevations of blood glucose, serum insulin, cholesterol, triglycerides, advanced glycation end products (AGEs), uric acid levels, insulin resistance index and blood pressure compared to control rats. Moreover, fructose increased oxidative stress in aortic tissues indicated by significant increases of malondialdehyde (MDA), expression of iNOS and reduction of reduced glutathione (GSH) content. These disturbances were associated with decreased eNOS expression, increased infiltration of leukocytes and loss of aortic vascular elasticity. Treatment with UDCA successfully ameliorated the deleterious effects of fructose. The protective effect of UDCA could be attributed to its ability to decrease uric acid level, improve insulin resistance and diminish oxidative stress in vascular tissues. These results might support possible clinical application of UDCA in MS patients especially those present with liver diseases, taking into account its tolerability and safety. However, further investigations on human subjects are needed before the clinical application of UDCA for this indication.     

Effect of Vitamin E Deficiency on Rat Brain Monoamine Metabolism

We investigated the effects of vitamin E deficiency on the monoamine metabolism in the rat brain. Male Wistar rats fed on the vitamin E deficient diet for 24 weeks were analyzed. At 28 weeks, they showed a reduced growth rate (52% of reduction), muscle atrophy, a motor weakness of hind limbs and disturbance of gait. The concentrations of monoamines, their precursors and metabolites in the brain were simultaneously determined using high performance liquid chromatography (HPLC) coupled with a coulometric detection with electrode array system. In addition, tryptophan hydroxylase activity was measured. The dopamine (p = 0.009) and serotonin (p = 0.04) levels in the brain stem of vitamin E deficients rats were significantly lower than in the controls, whereas their precursors tyrosine (p = 0.0009) and tryptophan (p = 0.0065) levels in the brain stem were significantly higher than in the controls. Moreover, tryptophan hydroxylase activity (p = 0.0005) in the brain stem of vitamin E deficient brains was significantly lower than in the controls. All statistical comparisons were done using non-parametric tests (Mann-Whitney U test). These results suggest that vitamin E deficiency may play a role in the disturbance of monoamine metabolism in rat brain.     

An Excellent Delivery System for Improving the Oral Bioavailability of Natural Vitamin E in Rats

This study set out to develop a novel and stable nanoemulsion formulation of natural vitamin E with increased oral bioavailability. The natural vitamin E nanoemulsion was prepared by a modified emulsification technique. The physicochemical characteristics of natural vitamin E nanoemulsion were characterized and its pharmacokinetics study was performed as well. The experimental results showed droplet diameters ranging from 20 to 400 nm (average, 87.7 nm) with a negative electrostatic potential (−23.5 ± 1.5 mv). The pharmacokinetics study of this nanoemulsion and corresponding soft capsule was carried out using noncompartment model method. Compared with the marketed soft capsule, the C_max of the natural vitamin E nanoemulsion was higher, while the T_max was shorter. Thus, plasma concentration–time profiles in rats dosed with nanoemulsion showed a 1.6-fold enhancement in the area under the curve of natural vitamin E compared with the marketed soft capsule. The antioxidative effects of the natural vitamin E nanoemulsion and the marketed soft capsule were also evaluated by the levels of superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration in serum and liver tissue. According to the SOD activity and the MDA concentration determined, the nanoemulsion was superior to the marketed soft as an antioxidative agent. The overall results demonstrated that the nanoemulsion drug delivery system could be a promising strategy for the delivery of natural vitamin E, which showed great potential for clinical application.Key word: Antioxidation, Nanoemulsion, Natural vitamin E, Oral bioavailability