胃饲乙醇预处理诱导肝脏缺血耐受性的可行性探讨

目的探讨胃饲乙醇预处理对肝脏缺血再灌流损伤的影响,并初步评价其预处理的可行性。方法40%乙醇胃饲Wistar大鼠。分组:①大鼠36只,随机分6组:A组8g/kg、B组7g/kg、C组6g/kg、D组5g/kg、E组4g/kg、正常组0g/kg;以中毒症状及肝组织病理为指标,判定大鼠乙醇急性中毒剂量。②大鼠78只,随机分为4组:正常对照组(N)、单纯乙醇组(E)、单纯缺血组(ISCH)、胃饲乙醇预处理组(EPC);采用尾叶转流下的肝缺血模型,于再灌流3、6、12、24h留取标本。结果急性胃饲乙醇≤5g/kg预处理后,动物中毒症状轻,无死亡;乙醇预处理可以在一定程度上减轻肝脏90min的缺血再灌流损伤。结论适当剂量的乙醇胃饲预处理是一种安全的预处理措施,有望成为增强肝脏对缺血再灌流损伤耐受性的一种较好的预处理方式。     

An improved technique for repeated gavage administration to rat neonates

ABSTRACT  The technique for gavage administration to rat nurslings was improved to allow determination of the direct effects of chemical substances in the nurslings. Rat neonates were treated with distilled water from postnatal day 1 through 20 using this technique. The viability of neonates during the administration period was comparable to that of untreated neonates. No adverse effects of this technique on the development of neonates were found, and no histological alterations of the esophagus or pharynx. Therefore, we conclude that use of our improved gavage administration method will contribute to ensuring successful neonatal development and thus allowing accurate assessment of the toxicological effects of test compounds on rat nurslings.     

Uterotrophic effect of a saturated fatty acid 17-ester of estradiol-17beta administered orally to juvenile rats

In comparison to estradiol-17beta, the naturally synthesized estradiol-17beta-17-fatty acid esters are potent estrogens when administered subcutaneously. A lipophilic character of estradiol-17-esters could partially protect them from metabolic inactivation. In order to compare their relative estrogenic potency when administered orally, the uterotrophic response to different dosages (0, 2.5, 25, 250 and 2500 nmol/kg BW/day) of estradiol-17beta and estradiol-17beta-17-stearate was assessed in juvenile Sprague-Dawley female rats. Estrogens were administered by oral gavage once a day for 6 days. On the 7th day uterus and vagina were dissected, weighed, and examined microscopically. At 2.5 and 25 nmol/kg BW/day, no difference was detected in the uterus weight compared to control animals which received the vehicle alone (corn oil). At 250 nmol/kg BW/day, the uterotrophic response was maximal in estradiol-17beta-17-stearate-treated animals (x2.40-2.70), whereas it was moderate in estradiol-17beta-treated rats (x1.86) at the same dosage. This differential weight gain effect of estradiol-17beta-17-stearate was correlated with typical microscopic changes in uterus and vagina. The results are in favour of a stronger estrogenic effect of orally given lipoidal estrogens compared to estradiol-17beta. This could be explained by a slower but sustained absorption of estradiol-17beta released from estradiol-17beta-17-stearate by esterases and/or by a facilitated transfer of esters in the lymphatic circulation.     

Quantitative biokinetics of titanium dioxide nanoparticles after intratracheal instillation in rats: Part 3

The biokinetics of a size-selected fraction (70?nm median size) of commercially available and ⁴⁸V-radiolabeled [⁴⁸V]TiO₂ nanoparticles has been investigated in healthy adult female Wistar-Kyoto rats at retention time-points of 1?h, 4?h, 24?h, 7?d and 28?d after intratracheal instillation of a single dose of an aqueous [⁴⁸V]TiO₂-nanoparticle suspension. A completely balanced quantitative biodistribution in all organs and tissues was obtained by applying typical [⁴⁸V]TiO₂-nanoparticle doses in the range of 40–240?μg·kg^?1 bodyweight and making use of the high sensitivity of the radiotracer technique. The [⁴⁸V]TiO₂-nanoparticle content was corrected for residual blood retained in organs and tissues after exsanguination and for ⁴⁸V-ions not bound to TiO₂-nanoparticles. About 4% of the initial peripheral lung dose passed through the air-blood-barrier after 1?h and were retained mainly in the carcass (4%); 0.3% after 28?d. Highest organ fractions of [⁴⁸V]TiO₂-nanoparticles present in liver and kidneys remained constant (0.03%). [⁴⁸V]TiO₂-nanoparticles which entered across the gut epithelium following fast and long-term clearance from the lungs via larynx increased from 5 to 20% of all translocated/absorbed [⁴⁸V]TiO₂-nanoparticles. This contribution may account for 1/5 of the nanoparticle retention in some organs. After normalizing the fractions of retained [⁴⁸V]TiO₂-nanoparticles to the fraction that reached systemic circulation, the biodistribution was compared with the biodistributions determined after IV-injection (Part 1) and gavage (GAV) (Part 2). The biokinetics patterns after IT-instillation and GAV were similar but both were distinctly different from the pattern after intravenous injection disproving the latter to be a suitable surrogate of the former applications. Considering that chronic occupational inhalation of relatively biopersistent TiO₂-particles (including nanoparticles) and accumulation in secondary organs may pose long-term health risks, this issue should be scrutinized more comprehensively.     

基于超高效液相色谱-四级杆-飞行时间质谱技术的清利湿热颗粒入血成分分析

目的：阐明灌胃给予清利湿热颗粒后大鼠体内吸收入血的化学成分。方法：借助超高效液相色谱-四级杆-飞行时间质谱(UPLC-Q-TOF-MS)技术,采用Agilent ZORBAX RRHD Eclipse XDB-C18色谱柱(2.1 mm×100 mm, 1.8μm),以0.1%甲酸水溶液-乙腈为流动相体系,梯度洗脱,进样量为2μL,在正、负离子模式下对处理后的空白血清和给药后0.5、1、2、4 h不同时间点的血清进行质谱检测。结果：通过与Natural Products HR-MS/MS Spectral Library 1.0数据库对比、文献分析以及质谱裂解规律从血清样品中鉴定出15个原型成分。结论：本研究为清利湿热颗粒标志性成分的选择提供了依据,初步确定了该产品发挥药效的物质基础,也为进一步揭示清利湿热颗粒的作用机制奠定基础。     

Oral Administration of Nicotinamide Mononucleotide Increases Nicotinamide Adenine Dinucleotide Level in an Animal Brain

As a redox-sensitive coenzyme, nicotinamide adenine dinucleotide (NAD⁺) plays a central role in cellular energy metabolism and homeostasis. Low NAD⁺ levels are linked to multiple disease states, including age-related diseases, such as metabolic and neurodegenerative diseases. Consequently, restoring/increasing NAD⁺ levels in vivo has emerged as an important intervention targeting age-related neurodegenerative diseases. One of the widely studied approaches to increase NAD⁺ levels in vivo is accomplished by using NAD⁺ precursors, such as nicotinamide mononucleotide (NMN). Oral administration of NMN has been shown to successfully increase NAD⁺ levels in a variety of tissues; however, it remains unclear whether NMN can cross the blood–brain barrier to increase brain NAD⁺ levels. This study evaluated the effects of oral NMN administration on NAD⁺ levels in C57/B6J mice brain tissues. Our results demonstrate that oral gavage of 400 mg/kg NMN successfully increases brain NAD⁺ levels in mice after 45 min. These findings provide evidence that NMN may be used as an intervention to increase NAD⁺ levels in the brain.     

急性甲醇中毒大鼠模型及其眼部改变的研究

【目的】探讨急性甲醇中毒大鼠模型的制作方法及其眼部改变，为研究中毒后视功能损害及救治方法建立基础。【方法】SD大鼠32只，随机分为A（低剂量甲醇组）、B（高剂量甲醇组）、C（生理盐水对照组）、D（空气对照组）4组，每组8只。A、B组吸入N2O／O2混合气及不同剂量甲醇灌胃，C组吸入N2O／O2混合气及生理盐水灌胃，D组置于正常空气中并按B组剂量给予甲醇灌胃，观察各组大鼠一般情况、体质量及眼部改变、静脉血甲醇浓度、视网膜电图和视网膜组织学改变。【结果】染毒大鼠反应迟钝、运动失调，视盘充血水肿、视网膜点状出血，A组大鼠体质量为（187±12）g，B组为（176±131g，较C、D对照组显著减轻（P〈0．05）；A组视网膜电图a、b波振幅分别为（87±13）μV、（187±38）μV，B组a、b波振幅分别为（53±19）μV、（132±39）μV，与对照组相比明显下降（P〈0．05）；视网膜在光镜下表现为各层细胞水肿、排列紊乱及空泡化；电镜下细胞凋亡，线粒体肿胀、嵴断裂；B组动物上述改变尤其明显。【结论】吸入N2O/O2混合气及甲醇灌胃可建立急性甲醇中毒的大鼠模型，出现典型的视网膜结构和功能改变。     

Liver tumor promoting ability of corn oil gavage in B6C3F1 male mice

In chronic carcinogenic bioassays, chemicals being tested with low water solubility have been administered via corn oil gavage. The present study examined the effect of chronic corn oil gavage on hepatic tumor formation in the B6C3F1 male mouse. Mice were initiated with diethylnitrosamine (DENA) either at 15 days of age with a single i.p. injection (5 μg/gbw) (protocol 1) or at 4 weeks of age via the drinking water (15 mg/l) for a duration of 3 weeks (protocol 2). At weaning (protocol 1) or 8 weeks of age (protocol 2) initiated and untreated mice were administered either corn oil at a dose of 0.15 ml via gavage (once a day, 5 days/wk) or saline (0.15 ml via gavage, once a day 5 days/wk). All mice were killed at 28 weeks of age and hepatic lesions were quantitated. Only mice exposed to DENA demonstrated hepatic tumors. Mice treated with DENA (at 15 days of age) and corn oil gavage exhibited a significant decrease in the number of hepatic adenomas compared with DENA (at 15 days of age) only treated mice. No difference was noted in the number of hepatic adenomas between mice treated with DENA (at 4 wks of age) and corn oil gavage and mice exposed to DENA (at 4 wks of age) only.     

香菇多糖、银耳多糖对荷瘤小鼠的免疫调节作用

目的：探讨复合多糖对S180荷瘤小鼠功能的影响。方法：（1）模型：S180荷瘤小鼠动物型；（2）免疫检测方法：溶血素测定，T淋巴细胞转化功能测定，腹腔巨噬细胞吞噬功能测定。（3）受试药物及给药方法；复合多糖口服。结果：复合多糖以0．75g/kg剂量灌胃荷瘤小鼠，可明显提高血清溶血清（P＜0．05）和T淋巴细胞转化功能（P＜0．05），表明该制剂可明显提高荷瘤小鼠的体液和细胞免疫功能，同时以1．5g/kg和0.75g/kg剂量可明显提高荷瘤小鼠的腹腔吞噬细胞功能（P＜0．05－0．01），表明该制剂对非特异性免疫有明显的促进作用。结论：复多糖对肿瘤机体免疫功能有明显的促进作用。