镁离子、维生素E抗氧化作用的研究

为研究镁离子、维生素E体内外抗氧作用,探讨镁离子抗氧化作用的机制,将3月龄昆明种小鼠70只随机分7组,设正常对照组、氧化对照组、63、42、21mmol／L镁保护组,镁和维生素E保护组,维生素E保护组,饲养10d,腹腔注射0．15％CCl4致小鼠肝损伤,观察镁离子、维生素E对小鼠肝匀浆中MDA、SOD、GSH含量的影响;在肝匀浆中加入FeSO4和H2O2诱导自由基的生成,观察镁离子、维生素E的抗氧化作用。结果表明,镁离子、维生素E能显著降低肝匀浆中脂质过氧化物MDA的含量,对SOD、GSH无明显影响。提示镁离子、维生素E能抑制自由基的生成,促进自由基清除作用。     

富硒肝对大鼠GSH-Px、GSH和游离巯基含量的影响

为观察富硒肝和亚硒酸钠对大鼠抗氧化能力的影响。将6只大鼠分为两组:A组用亚硒酸钠[按Se元素计,6μg/(只.d)]灌胃,B组用富硒肝[按Se元素计,6μg/(只.d)]灌胃。于灌胃第0、4、8、12、16、20天内眦采血,测定血浆和血细胞内液中GSH-Px活力以及GSH、游离巯基的含量。结果表明:①给药20 d后A、B组血浆和血细胞内液GSH-Px活力和GSH含量均明显高于灌胃前(P0.05);②A、B组血浆中游离巯基的含量略有增加,而血细胞内含量则大幅降低(P0.05)。结论:经口给予富硒肝可诱导大鼠产生较多的抗氧化物质,增强大鼠的抗氧化能力。其作用可达同剂量亚硒酸钠水平。     

原子荧光光谱法测定褪黑素治疗组兔肝脏硒含量

为探讨褪黑素对实验性动脉粥样硬化兔肝脏组织中硒含量的影响,用高脂饮食复制兔动脉粥样硬化,然后给予褪黑素建立治疗组模型,获取肝脏,用硝酸、过氧化氢混合液微波消解样品,采用原子荧光光谱法测定肝脏组织中硒的含量。结果表明,正常组、高脂组和褪黑素治疗组硒在肝脏组织中质量分数分别为3.31、2.14和1.34 mg/kg。提示给予褪黑素治疗后,褪黑素治疗组的硒平均含量比高脂组的平均含量降低37.4%,所以褪黑素对肝脏硒的吸收具有明显的抑制作用。     

低剂量硝酸镧对小鼠肾脏自由基防御机能的影响

通过采用肾组织匀浆生化测定法, 观察不同剂量硝酸镧灌胃一个月后, 小鼠肾组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、脂质过氧化物(LPO)、谷胱甘肽过氧化物酶(GSH-PX)含量的变化, 探讨了低剂量硝酸镧的抗氧化作用; 结果表明 雌性、雄性小鼠20.0, 10.0 mg*kg-1 Cu-ZnSOD和CAT的含量均较对照组明显降低; 而GSH-Px和LPO的含量均较对照组显著升高. 雌性、雄性小鼠0.1, 0.2, 2.0 mg*kg-1组Cu-ZnSOD, CAT, GSH-Px和LPO的含量与对照组无显著性差异. 较高剂量(20.0, 10.0 mg*kg-1)的硝酸镧的直接损伤可使小鼠肾脏脂质过氧化反应增强, 清除自由基的能力下降. 较低剂量(0.1, 0.2, 2.0 mg*kg-1)的硝酸镧对小鼠肾脏自由基的生成和清除无影响.     

二氯苯染毒对小鼠组织中Zn、Cu、Fe含量的影响

采用亚急性试验,探讨对二氯苯（P—DCB）对小鼠组织中Zn、Cu、Fe的影响。选用36只小鼠,雌雄各半,随机分成3组,每组12只,分别给予P—DCBO（对照组）、450、900mg·kg^-1,每天灌胃染毒1次,连续7d,染毒结束后24h处死动物并称体质量、肝、肾质量,计算脏器系数。用火焰原子吸收法测定肝脏、血液和肾脏中Zn、Cu、Fe含量。与对照组相比,各染毒组体质量无明显变化。各组肝体系数无差异,但染毒组肾体系数明显高于对照组（P〈O．05）。900mg·kg^-1组肝脏中Zn含量及w（Zn）／w（Cu）值较450mg·kg^-1组有明显升高。与对照组相比,各染毒组血液中Zn含量呈现下降趋势,900nag·kg^-1组较对照组明显下降（P〈0．05）。900mg·kg^-1组肾脏中Cu质量分数明显低于450mg·kg^-1组,Fe质量分数则较对照组及450mg·kg^-1组均有降低,P—DCB可影响小鼠组织中元素Zn、Cu、Fe的含量及不同器官的再分布,提示微量元素失衡可能是P—DCB毒作用的重要机制。     

硫酸氧钒毒性的核磁共振代谢组学方法研究

采用基于核磁共振(NMR)的代谢组学方法,结合生化指标分析及组织病理学检测,研究了具有类胰岛素活性的硫酸氧钒(VOSO4)对Wistar大鼠的毒性作用.通过不同剂量的VOSO4对Wistar大鼠连续灌胃给药16d,收集大鼠的血清和尿液,并采集样品的1H NMR谱进行多变量数据统计分析来辨识其特征代谢物,然后采用TICL(a web Tool for automatic Interpretation of Compound List)方法建立特征代谢物的代谢网络模型,分析受影响的主要代谢途径及其相互关系.研究结果表明:高剂量组(45mg/kg)和低剂量组(15mg/kg)的特征代谢物含量与对照组存在明显的差异;与对照组相比,高剂量和低剂量组血清中乳酸、肌氨酸酐以及牛磺酸等代谢物的含量增加,尿液中氧化三甲胺(TMAO)、肌酐、牛磺酸和甘氨酸等代谢物的含量增加,并呈现显著的剂量依赖关系;给药组中乙酸和琥珀酸的含量都降低.这些结果说明VOSO4可能影响大鼠体内的糖代谢、脂类代谢及肠道菌群代谢等多个代谢系统,高剂量的VOSO4会导致肝脏毒性和肾脏损伤.     

~(125)Ⅰ内照射的小鼠血清中5种微量元素水平变化

对小鼠灌喂含125Ⅰ放射性物质,建立放射性内照射模型,应用原子吸收光谱法测定了低、中、高辐射源剂量组及对照组小鼠血清中Zn、Cu、Fe、Mg、Mn的含量。结果表明,采用辐射源灌喂的小鼠血清中5种微量元素含量均低于没有灌喂辐射源的对照组,5种微量元素的含量随着辐射剂量的增加而降低。结果提示,通过科学膳食补充人体必需微量元素,对于积极防御辐射对机体健康产生的危害极为重要。     

125I内照射的小鼠血清中5种微量元素水平变化

对小鼠灌喂含125I放射性物质,建立放射性内照射模型,应用原子吸收光谱法测定了低、中、高辐射源剂量组及对照组小鼠血清中Zn、Cu、Fe、Mg、Mn的含量.结果表明,采用辐射源灌喂的小鼠血清中5种微量元素含量均低于没有灌喂辐射源的对照组,5种微量元素的含量随着辐射剂量的增加而降低.结果提示,通过科学膳食补充人体必需微量元素,对于积极防御辐射对机体健康产生的危害极为重要.     

氟化钠对小鼠骨髓细胞微核率的影响

为探讨氟化钠对小鼠骨髓细胞微核率的影响,选取50只小鼠随机分为5组:氟化钠染毒高剂量组(34 mg/kg)、中剂量组(17 mg/kg)、低剂量组(8.5 mg/kg)、环磷酰胺阳性对照组(50 mg/kg)、生理盐水空白对照组,采用经口灌胃染毒,1 次/d,连续2 d,第3天处死小鼠取胸骨骨髓制片观察小鼠骨髓细胞微核...     

肝损伤代谢组学模型的构建及其中药提取物水飞蓟宾治疗的评价

利用四氯化碳致肝损伤动物模型,以尿液为样本,采用构建的色谱基线漂移和外源性代谢物信号消除的方法,获得了内源性代谢物总离子流色谱,建立了肝损伤代谢组学模型,该模型表达的四氯化碳致毒特征与组织细胞显微特征和血清学指标一致。当模型动物给予水飞蓟宾治疗时,治疗前的代谢组学分类特征与模型组一致,治疗后与正常对照组一致;代谢组学表征的"治疗后肝损伤回调"特征与肝组织显微成像特征一致,然而血清学指标虽然也明显回调,但还未回调到与正常对照组一致。由此表明,代谢组学疗效评价的灵敏性与"损伤性"的作为"金标准"的组织显微成像一致,而明显高于常规血清学检测。建立的代谢组学模型实现了非损伤、准确、灵敏的中药治疗评价。     

雄黄染毒后大鼠脑组织中氨基酸类神经递质含量的变化

研究了雄黄对大鼠脑组织氨基酸类神经递质含量的影响.将32只Wistar大鼠随机分为对照组(0.5%CMC-Na)以及低剂量(0.3g/kg)、中剂量(0.9g/kg)、高剂量(2.7g/kg)雄黄染毒组,通过连续灌胃给予雄黄混悬液两周.采用高效液相色谱-柱前衍生化法测定了大鼠脑组织中氨基酸类神经递质含量的变化.结果表明,与对照组比较,低剂量组大鼠脑组织中丝氨酸、甘氨酸和γ-氨基丁酸含量明显增加.中、高剂量组大鼠脑组织中同型半胱氨酸、谷氨酰胺、丝氨酸和天冬氨酸含量明显比对照组的低.总体而言,雄黄可对大鼠脑组织氨基酸类神经递质产生影响,氨基酸类神经递质可能是雄黄毒性作用的靶点之一.     

Glutathione Isopropyl Ester Reduces UVB-lnduced Skin Damage in Hairless Mice

Abstract— The protective effect of administration of glutathione (GSH) isopropyl ester on photodamage, such as lipid peroxidation, inflammation and tumorigenesis induced by UV exposure (290–400 nm, max. 312 nm), was investigated using hairless mice. Pretreatment with 20 mg/kg GSH isopropyl ester prevented the increases of thiobarbituric acid-reactive substance (TBARS) formation in skin and serum sialic acid, indices of lipid peroxidation and inflammatory reaction, respectively, which were caused by a single dose (15 kj/m²) of UV irradiation. The level of epidermal GSH in skins of the GSH ester-treated mice was maintained within normal limits. When mice were exposed to UV at a dose of 2 kj/m², three times weekly, skin tumors developed in all of them after 25 weeks. The formation of skin tumors was significantly inhibited by administration of 10 mg/kg GSH ester prior to each UV irradiation for 25 weeks. Moreover, the increases of cutaneous TBARS and serum sialic acid in the tumor-bearing mice were also prevented by continuous pretreatment with GSH ester. Even after 24 weeks, the epidermal GSH content of the pretreated mice was mostly retained compared to nonirradiated mice. However, administration of GSH prior to acute or chronic UV irradiation had no effect on the UV-induced damage. The present results suggest that the protection from photo-damage afforded by pretreatment with GSH ester is due to maintenance of a normal GSH level.     

Evaluation of the immunity activity of glycyrrhizin in AR mice

In this study, we evaluated effect of glycyrrhizin on immunity function in allergic rhinitis (AR) mice. The AR mice model were induced by dripping ovalbumin in physiological saline (2 mg mL?1, 10 μL) into the bilateral nasal cavities using a micropipette. After the AR model was induced, mice were randomly divided into six groups: the normal control, model, lycopene 20 mg kg?1 (as positive control drug) group, and glycyrrhizin 10, 20, 30 mg kg?1 groups. After the sensitization day 14, lycopene (20 mg/kg BW) and glycyrrhizin (10, 20 and 30 mg/kg BW) were given orally for 20 days once a day. Mice in the normal control and model groups were given saline orally once a day for 20 days. Results showed that glycyrrhizin treatment could dose-dependently significantly reduce blood immunoglobulin E (IgE), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6), nitrous oxide (NO), tumor necrosis factor-alpha (TNF-α) levels and nitrous oxide synthase (NOS) activity and enhance blood immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), interleukin-2 (IL-2) and interleukin-12 (IL-12) levels in AR mice. Furthermore, glycyrrhizin treatment could dose-dependently significantly enhance acetylcholinesterase (AchE) activity and reduce substance P (SP) level in peripheral blood and nasal mucosa of AR mice. We conclude that glycyrrhizin can improve immunity function in AR mice, suggesting a potential drug for the prevention and therapy of AR.     

氟化钠对雄性小鼠精子畸形的影响

为探讨氟化钠对雄性小鼠精子畸形的影响,选取50只成年雄性小鼠随机分为5组：氟化钠染毒高剂量组（34mg／kg）、中剂量组（17mg／kg）、低剂量组（8．5mg／kg）、环磷酰胺阳性对照组（50mg／kg）、生理盐水空白对照组,采用经口灌胃染毒,1次／d,连续5d,于首次染毒后的第35天颈椎脱臼将小鼠处死,取睾丸和附睾称质量,计算脏器系数;同时取附睾制片,观察精子形态,计数小鼠精子畸形率。结果表明,氟化钠染毒各组睾丸、附睾脏器系数与空白对照组比较,差别无统计学意义（P〉0．05）,染毒各组精子畸形率普遍高于空白对照组,差别有统计学意义（P〈0．001）,且随着染毒剂量的增加精子畸形率也有相应升高,呈现一定的剂量一反应关系（r=0．954,F=20．098,P〈0．05,R^2=0．909）。提示氟化钠能使雄性小鼠精子畸形率明显升高,具有一定的生殖毒性,能影响小鼠生殖功能,对小鼠生殖功能造成损害。     

A Novel Galantamine-Curcumin Hybrid as a Potential Multi-Target Agent against Neurodegenerative Disorders

The acetylcholinesterase (AChE) inhibitors are the main drugs for symptomatic treatment of neurodegenerative disorders like Alzheimer’s disease. A recently designed, synthesized and tested hybrid compound between the AChE inhibitor galantamine (GAL) and the antioxidant polyphenol curcumin (CU) showed high AChE inhibition in vitro. Here, we describe tests for acute and short-term toxicity in mice as well as antioxidant tests on brain homogenates measured the levels of malondialdehide (MDA) and glutathione (GSH) and in vitro DPPH, ABTS, FRAP and LPO inhibition assays. Hematological and serum biochemical analyses were also performed. In the acute toxicity tests, the novel AChE inhibitor given orally in mice showed LD₅₀ of 49 mg/kg. The short-term administration of 2.5 and 5 mg/kg did not show toxicity. In the ex vivo tests, the GAL-CU hybrid performed better than GAL and CU themselves; in a dose of 5 mg/kg, it demonstrates 25% reduction in AChE activity, as well as a 28% and 73% increase in the levels of MDA and GSH, respectively. No significant changes in blood biochemical data were observed. The antioxidant activity of 4b measured ex vivo was proven in the in vitro tests. In the ABTS assay, 4b showed radical scavenging activity 10 times higher than the positive control butylhydroxy toluol (BHT). The GAL-CU hybrid is a novel non-toxic AChE inhibitor with high antioxidant activity which makes it a prospective multitarget drug candidate for treatment of neurodegenerative disorders.     

基于核磁共振氢谱代谢组学研究黄连解毒汤对胰岛素抵抗大鼠棕色脂肪组织代谢组的影响

采用基于核磁共振氢谱(¹H NMR)的代谢组学方法, 研究了黄连解毒汤(HJD)对高果糖诱导胰岛素抵抗大鼠模型棕色脂肪代谢组的影响. 选取Wistar大鼠32只, 适应7 d后随机分为正常对照组、 模型组、 阳性药物对照组和黄连解毒汤组, 每组8只. 正常对照组给予纯净水喂养, 其它3组给予100 g/L的果糖水喂饲. 28 d后, 4组大鼠除了继续给予100 g/L的果糖水喂养外, 阳性对照组和黄连解毒汤组同时分别给予阿托伐他汀10 mg/(kg·d)和HJD水煎剂3.175 g/(kg·d)灌胃, 正常对照组和模型组给予一定体积的生理盐水灌胃, 整个实验持续56 d. 取各组大鼠棕色脂肪组织(BAT), 采集各组组织提取液的¹H NMR谱, 运用主成分分析法(PCA)分析. 与正常对照组相比, 在模型组中乳酸、 胆碱、 磷脂胆碱/甘油磷脂胆碱、 肌酸/肌酸酐、 牛磺酸和肌苷的含量升高, 脂质含量降低; 黄连解毒汤组逆转了模型组中上述各代谢物的变化, 且引起肌醇升高, 均具有统计学意义. 实验结果表明, 黄连解毒汤能够逆转机体能量代谢、 减轻细胞膜受损以及降低肝肾损伤, 初步阐明了黄连解毒汤对胰岛素抵抗状态下棕色脂肪组织代谢的调控作用.     

雄黄对大鼠脑组织能量代谢的影响

将32只Wistar大鼠随机分为对照组(口服0.5%羧甲基纤维素钠溶液)以及低剂量(0.3g/kg)、中剂量(0.9g/kg)和高剂量(2.7g/kg)雄黄混悬液处理组,通过6周连续灌胃给服雄黄混悬液,采用高效液相色谱法测定大鼠脑组织中三磷酸腺甙(ATP)的含量,研究了雄黄对大鼠脑组织能量代谢的影响.结果表明,与对照组比较,雄黄染毒组大鼠脑组织中ATP含量均呈下降趋势(P<0.05),不同剂量组间未表现明显差异(P>0.05).这表明雄黄对大鼠脑组织能量代谢具有一定的抑制作用.     

Hypoglycemic and hypolipidemic effects of polyphenols from burs of Castanea mollissima Blume

Substantial evidence suggests that phenolic extracts of Castanea mollissima spiny burs (CMPE) increase pancreatic cell viability after STZ (streptozotocin) treatment as a result of their antioxidant properties. In the present study, the hypoglycemic and hypolipidemic activities of CMPE were studied in normal and STZ-induced diabetic rats CMPE were orally administrated at doses of 150 and 300 mg/kg twice a day for 12 consecutive days. Serum glucose, triglyceride, total cholesterol, HDL- and LDL-cholesterol levels, malondialdehyde (MDA) level and SOD activity in liver, kidney, spleen and heart tissues were measured spectrophotometrically. In normal rats, no significant changes were observed in serum glucose, lipid profiles and tissue MDA and GSH levels after orally administration of CMPE. In diabetic rats, oral administration of CMPE at a dose of 300 mg/kg caused significant decreases in serum glucose, triglyceride, total cholesterol, LDL-cholesterol levels, as well as MDA and GSH levels in spleen and liver tissues. However, the 300 mg/kg dosage caused a significant body weight loss in both normal and diabetic rats. The observed effects indicated that CMPE could be further developed as a drug to prevent abnormal changes in blood glucose and lipid profile and to attenuate lipid peroxidation in liver and spleen tissues.     

Nephroprotective effects of 4-4(hydroxyl-3 methoxyphenyl)-2-butane against sodium tellurite induced acute kidney dysfunction by attenuating oxidative stress and inflammatory cytokines in rats

The aim of this study was to elucidate the protective action mechanism of 4-4(hydroxyl-3-methoxyphenyl)-2-butane against Sodium tellurite (ST) induced nephrotoxicity in rats. ST is a hazardous substance used in metallurgical and glassware industries, but its renal toxicities have not been well established before. Rats were distributed into four groups, six rats contain in each group. Normal control group given only vehicles only, toxic group given ST 8.5 mg/kg p o, treated groups given ST and 4-(hydroxyl-3-methoxyphenyl)-2-butane(100 mg/kg bwt), and positive control given only treatment drug 4-(hydroxyl-3-methoxyphenyl)-2-butane (100 mg/kg bwt) daily for 14 days. ST administration increases an alteration in biochemical, oxidative stress, cytokines markers, and morphological changes in toxic group. When it was treated with 4-(hydroxyl-3- methoxyphenyl)-2-butane significantly (p < 0.5) restores all these changes such as biochemical markers, antioxidant, inflammatory cytokines, and histopathological improvements in treated group as compared to toxic group. No significant (p > 0.05) changes have been seen in positive control as compared to normal control. In conclusion, 4(hydroxyl-3 methoxyphenyl)-2-butane successfully defended the kidney from oxidative stress, inflammatory cytokines and necrosis against ST intoxication. Thus, significant improvements were reflected and confirms with the improvement in histopathological changes.