迎春花提取物对小鼠SOD活性及MDA含量的影响

目的 研究迎春花提取物对小鼠超氧化物歧化酶（SOD）活性及丙二醛（MDA）含量的影响.方法 取小鼠50只,随机分为5组,生理盐水对照组,维生素E对照组,低、中、高剂量迎春花提取物组.给药20 d,心脏取血,分离血清;颈椎脱臼处死小鼠,取心、脑、肝等组织,分别检测血清、心、脑、肝等组织中SOD的活性和MDA的含量.结果 迎春花提取物对小鼠血清、心、肝等组织中SOD活性显著升高,血清、心、脑、肝等组织中MDA含量显著下降.结论 迎春花提取物具有清除体内脂质过氧化物的作用,能改善小鼠体内异常的过氧化状态,减轻机体的过氧化损伤.     

复方甘草酸苷对大鼠酒精性肝损伤的预防作用研究

目的探讨复方甘草酸苷对大鼠酒精性肝损伤的防治效果。方法选取78只大鼠随机分为六组,空白组,模型组,复方甘草酸苷低、中、高剂量组及阳性对照组即葵花护肝片组各13例,检测各组大鼠血清ALT及AST,测定SOD、MDA和GSH,并取肝组织进行HE染色,采用光镜观察各组大鼠肝组织及肝细胞结构等。结果模型组与空白组比较,血清ALT和AST活性明显升高(P*<0.05)。与模型组比较,复方甘草酸苷各剂量组与阳性对照组血清ALT和AST活性明显降低(P**<0.05)。模型组与空白组比较,肝组织SOD活性及GSH均降低,MDA升高(P<0.05);与模型组比较,复方甘草酸苷各剂量组与阳性对照组SOD活性及GSH水平升高,而MDA降低(P<0.05)。复方甘草酸苷各剂量组相对模型组而言,大鼠活动较多,整体状态较好,食欲较好。结论复方甘草酸应用于酒精性损伤大鼠中,可保护肝细胞,减轻肝损害。     

大豆苷元对谷氨酸体外诱导海马神经元损伤大鼠的保护作用

［摘要］目的探讨大豆苷元对谷氨酸体外诱导原代培养大鼠海马神经元损伤的作用及机制. 方法通过对海马神经元的超氧化物歧化酶（SOD）和丙二醛（MDA）生化测试及胞内游离钙浓度测定,观察大豆苷元对谷氨酸诱导海马神经元损伤的作用. 结果大豆苷元呈浓度依赖性的拮抗由400 μmol&;#8226;L 1谷氨酸诱导的［Ca2+］i 增高、MDA生成,并提高SOD活性.结论大豆苷元对谷氨酸体外诱导大鼠海马神经细胞损伤具有保护作用,可能与缓解胞内Ca2+超载、提高神经元抗氧化能力有关.     

复方甘草酸苷对大鼠酒精性肝损伤的预防作用研究

目的探讨复方甘草酸苷对大鼠酒精性肝损伤的防治效果。方法选取78只大鼠随机分为六组,空白组,模型组,复方甘草酸苷低、中、高剂量组及阳性对照组即葵花护肝片组各13例,检测各组大鼠血清ALT及AST,测定SOD、MDA和GSH,并取肝组织进行HE染色,采用光镜观察各组大鼠肝组织及肝细胞结构等。结果模型组与空白组比较,血清ALT和AST活性明显升高(*P<0.05).与模型组比较,复方甘草酸苷各剂量组与阳性对照组血清ALT和AST活性明显降低(**P<0.05)。模型组与空白组比较,肝组织SOD活性及GSH均降低,MDA升高(P<0.05);与模型组比较,复方甘草酸苷各剂量组与阳性对照组SOD活性及GSH水平升高,而MDA降低(P<0.05)。复方甘草酸苷各剂量组相对模型组而言,大鼠活动较多,整体状态较好,食欲较好。结论复方甘草酸应用于酒精性损伤大鼠中,可保护肝细胞,减轻肝损害。     

白芍总苷对NAFLD大鼠肝脏的保护作用及其机制研究

目的研究白芍总苷对NAFLD模型大鼠肝脏保护的机制。方法 SD大鼠50只,随机分为正常对照组10只,模型组40只。高脂饲料喂养建模后,模型组随机分为模型对照组、非诺贝特组、白芍总苷高剂量组、白芍总苷低剂量组各10只。连续灌胃给药4周后,测定大鼠血清中ALT、AST、GST、SOD和GSH-PX酶的活性及MDA含量;测定血清中IL-1、TNF-α和TGF-β的水平;各组取肝脏做HE染色,观察肝脏组织学病变。结果与正常对照组比较,NAFLD模型对照组大鼠ALT、AST、GST活性和IL-1、TNF-α、TGF-β含量显著升高,经非诺贝特和白芍总苷干预后,模型组大鼠的ALT、AST、GST活性和IL-1、TNF-α、TGF-β含量均降低回正常水平,差异有统计学意义(P<0.05);与正常对照组比较,NALFD模型大鼠SOD、GSH-PX活性显著降低,MDA含量明显升高,干预治疗后,模型组大鼠SOD、GSH-PX活性大大提高,MDA含量显著降低(P<0.05)。结论白芍总苷对高脂引起的NAFLD模型大鼠有肝脏保护作用,其作用机制可能与其提高抗氧化能力、降低异常细胞因子水平有关。     

番茄红素及维生素E和C合用对庆大霉素大鼠肾毒性预防作用的比较

目的比较番茄红素及维生素(Vit)E和VitC合用对庆大霉素大鼠肾毒性的预防作用。方法雄性SD大鼠给予庆大霉素140 mg.kg-1(ip),连续7 d。预防组同时予以番茄红素20 mg.kg-1(ig)或Vit E 50 mg.kg-1和Vit C 200 mg.kg-1(ig)。给药7 d后,测定大鼠血清尿素氮(BUN)、血肌酐(SCr)和尿肌酐含量,计算肌酐清除率(CCr);测定尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)活性,肾组织中超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性及丙二醛(MDA)含量;HE染色观察肾脏病理改变。结果与正常对照组比较,庆大霉素组大鼠血清BUN和SCr含量升高,CCr降低,尿NAG活性升高,肾组织MDA水平增加,SOD和CAT活性降低,肾脏病理改变明显。给予番茄红素,或Vit E和Vit C合用明显减轻上述改变,番茄红素的作用较Vit E和Vit C合用更为明显。结论番茄红素及Vit E和Vit C合用均可能通过抗氧化应激作用减轻庆大霉素大鼠肾毒性,番茄红素的作用可能优于Vit E和Vit C合用。     

大豆异黄酮对高胆固醇血症大鼠血及肝脏MDA含量和SOD活力的影响(英文)

目的 :研究大豆异黄酮对高胆固醇血症大鼠血液及肝脏丙二醛 (MDA )、超氧化物歧化酶(SOD)的影响。方法 :根据血胆固醇水平 ,5 0只雄性Wistar大鼠随机分为 5组 ,正常对照组 (NC)、高胆固醇血症对照组 (HC)和 3个大豆异黄酮治疗组。除正常对照组以外 ,各组均喂以高胆固醇饲料。同时 ,3个治疗组分别灌胃给予 30 ,6 0 ,12 0mg·kg- 1大豆异黄酮 ,对照组给予相应的溶媒 ,持续 9wk。实验结束时 ,分离血清、红细胞 ,取出肝脏 ,制备肝匀浆。采用黄嘌呤氧化酶法测定红细胞和肝匀浆SOD活力 ,以硫代巴比妥酸法测定血清和肝匀浆MDA含量。结果 :与正常对照组比较 ,高胆固醇血症对照组大鼠红细胞及肝匀浆SOD活力明显降低。大豆异黄酮 6 0和 12 0mg·kg- 1组大鼠红细胞及肝脏SOD活力比高胆固醇血症对照组明显升高 (P <0 .0 1和P <0 .0 5 )。高胆固醇血症对照组大鼠血清及肝匀浆MDA含量与正常对照组比较明显升高。与高胆固醇血症对照组比较 ,大豆异黄酮 30和 6 0mg·kg- 1组大鼠血清MDA含量及 30和 12 0mg·kg- 1组大鼠肝脏MDA含量明显降低 (P <0 .0 5 )。结论 :对于高胆固醇血症大鼠红细胞及肝脏SOD活力的降低及血清和肝脏MDA水平的升高 ,能被大豆异黄酮部分逆转     

连翘苷元对四氯化碳大鼠急性肝损伤的保护作用

目的探讨连翘苷元对四氯化碳(CCl4)所致急性肝损伤的保护作用。方法用CCl4诱导化学性急性肝损伤模型,测定血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)水平;肝脏组织切片,苏木精-伊红(HE)染色,光镜观察病理学改变;用试剂盒测定肝组织中SOD、GSH-Px和GSH的活性及脂质过氧化产物MDA含量。ELISA法检测血清中TNF-α、IL-8含量。结果在CCl4诱导的大鼠急性肝损伤模型中,连翘苷元(0.05、0.15、0.5mg·kg-1,sc)明显降低血清ALT、AST和TBIL水平;明显改善肝脏病理组织状况;连翘苷元(0.05、0.15、0.5 mg·kg-1,sc)明显降低CCl4诱导的急性肝损伤大鼠的肝组织匀浆中MDA的含量,明显增加SOD、GSH-Px和GSH的活性。连翘苷元(0.15、0.5 mg·kg-1,sc)明显降低TNF-α、IL-8含量。结论连翘苷元对CCl4诱导大鼠急性肝损伤具有保护作用,该作用与其增加肝组织中抗氧化酶的活性、降低脂质过氧化水平、降低TNF-α、IL-8等促炎因子水平有关。     

芍药苷对异丙肾上腺素诱导大鼠心肌重构的干预作用

目的通研究芍药苷(PEF)对异丙肾上腺素(ISO)诱导大鼠心肌重构的干预作用,并探讨可能的作用机制。方法雄性SD大鼠32只,随机分成4组,即对照组、模型组、芍药苷低剂量组、高剂量组(40,80 mg·kg~(-1)),模型组和高、低剂量组连续皮下注射ISO(5 mg·kg~(-1))1周,对照组注射等比例生理盐水;造模同日起,高、低剂量组灌胃芍药苷,对照组和模型组灌胃等体积的生理盐水,连续14 d。末次给药后30 min,水合氯醛麻醉大鼠,腹主动脉取血测定羟脯氨酸;处死大鼠,取出心脏分离左心室并称重,测定左心室指数;Masson染色观察组织中心肌纤维化程度;心肌匀浆测定组织超氧化物歧化酶(SOD)、丙二醛(MDA)及Ⅰ型胶原蛋白的含量。结果模型组血清羟脯氨酸、左心室指数及心组织MDA、Ⅰ型胶原蛋白含量均高于对照组(P<0.05),芍药苷给药组均低于模型组(P<0.05)。在Masson染色中,模型组心肌组织中的胶原明显增加;芍药苷低、高剂量组心肌组织中胶原纤维减少,不同剂量心肌组织胶原纤维减少不同,表现出对ISO引起大鼠心肌纤维化的干预作用。模型组大鼠组织SOD的活力降低;而芍药苷高、低剂量均可明显提高SOD活性模型组。结论芍药苷对ISO致大鼠心肌重构具有一定的干预作用,其作用机制可能与抗氧化作用有关。     

枸杞多糖对高脂饮食诱导的脂肪肝大鼠模型的影响

目的 观察枸杞多糖(lycium barbarum polysaccharide,LBP)对高脂饮食大鼠非酒精性脂肪肝的影响及可能的机制.方法 32只雄性Wistar大鼠随机分成4组:正常对照组、模型组和LBP高、低剂量组.采用喂高脂饲料复制大鼠非酒精性脂肪肝模型.观察不同处理组大鼠血清ALT、AST、血脂、肝脂质、肝组织超氧化物歧化酶(SOD)活性、还原型谷胱甘肽(GSH)和丙二醛(MDA)的含量以及肝脏病理形态学的变化.结果 与非酒精脂肪肝模型组相比,LBP干预组血清ALT下降,以高剂量组明显(P＜0.05),血清总胆固醇(TCh)和LDL-Ch明显下降(P＜0.05),血清HDL-ch呈升高趋势,但无显著性差异(P＞0.05),肝内甘油三酯和TCh含量下降(P＜0.05),肝内脂肪变性和炎症程度均明显减轻(P＜0.05),肝内MDA含量均显著降低(P＜0.05),肝内SOD活性和GSH含量升高,高剂量组明显(P＜0.05).结论 LBP可明显减轻高脂饮食诱导的大鼠非酒精性脂肪肝,其机制可能与其抗氧化作用有关.     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

益生菌与肿瘤防治

益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.     

Self-stimulation and amphetamine: Tolerance to d and l isomers and cross tolerance to cocaine and methylphenidate

The effects of the d and l isomers of amphetamine on self-stimulation responding were tested following acute and chronic administration. Tolerance and post-drug depression of responding occurred in tests with both isomers, indicating no role for p-hydroxynorephedrine (PHN) which is one of the metabolites of d-amphetamine. In the second experiment, d-amphetamine, methylphenidate and cocaine all produced quantitatively and qualitatively similar effects on self-stimulation responding following acute administration. Following chronic administration of d-amphetamine, animals showed tolerance to all three drugs, indicating cross-tolerance among them. These data are consistent with an hypothesis that tolerance and post-drug depression following chronic amphetamine treatment are the result of decreases in postsynaptic receptor sensitivity, which would lead to a decreased effectiveness of all three drugs, regardless of their pre-synaptic mechanisms.     

Isolation and characterization of glycosylated and non-glycosylated prolactins from alligator and crocodile

Two molecular forms of prolactin (PRL). glycosylated and non-glycosylated, were isolated from pituitary glands of two reptiles, alligator and crocodile. The reptilian PRLs were extracted under alkaline conditions from the precipitate obtained after pituitaries were first extracted with 0.25 m sucrose, 1 mM NH₄HCO₃, pH 6.3. Purification was performed by ion exchange chromatography on DE-52, gel filtration on Sephadex G-75 superfine, and reversed phase high performance liquid chromatography. Two forms of both alligator and crocodile PRL, designated PRLI and PRLII, with molecular weights of 26000 and 24000 were isolated. Alligator and crocodile PRLI and PRLII were stained specifically in immunoblots with anti-sea turtle PRL and anti-ostrich PRL. Sequence analysis revealed that both forms of alligator and crocodile PRLs consisted of 199 amino acid residues with a glycosylation consensus sequence (Asn-Ala-Ser) at position 60 in alligator and crocodile PRLs with a molecular weight of 26000 (PRLI). In contrast, Thr was substituted for Asn at position 60 in the PRLs with a molecular weight of 24000 (PRLII). The sequences of alligator PRLs differed from crocodile PRLs only in position 134: Val for alligator PRLs and He for crocodile PRLs. There is a high degree of structural conservation between the reptilian PRLs isolated in this study and avian PRL; each showed 92% sequence identity with chicken PRL and 89% with turkey PRL.