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1.
The kinetic constants for large neutral amino acid (LNAA) transport across the blood-brain barrier (BBB) of conscious rats were determined in four brain regions: cortex, caudate-putamen, hippocampus, and thalamus-hypothalamus. Indwelling external carotid artery catheters allowed for single-bolus (200 microliters) injections directly into the arterial system of unanesthetized and lightly restrained animals. Our results showed lower brain uptake index values for conscious rats compared to previous reports for anesthetized animals which are consistent with higher rates of cerebral blood flow in the conscious animals. Km values were lower in the conscious animals and ranged from 29% to 87% of the Km values in pentobarbital-anesthetized animals whereas the KD values were about twofold higher in the conscious animals. No apparent regional differences were observed. Influx rates were determined which take into consideration flow rates and plasma amino acid concentrations. Our results showed an average amino acid influx value of 5.2 nmol/min/g, which is 53% higher than the average influx in pentobarbital-anesthetized animals. The present results in conscious animals regarding the low Km of LNAA transport across the BBB lend further support to the importance of fluctuations in plasma amino acid concentrations and LNAA transport competitive effects on brain amino acid availability.  相似文献   

2.
探究叶酸对高尿酸血症大鼠肠道微生物的影响,为治疗高尿酸血症提供新思路。将SPF 级雄性大鼠分为空白对照组、模型组和叶酸组,采集大鼠的粪便样本,采用16S rRNA高通量测序技术分析肠道微生物的多样性、群落组成以及结构的变化。研究结果显示,Alpha多样性和Beta多样性分析表明,空白对照组、模型组和叶酸组大鼠粪便中微生物多样性和群落组成存在明显差异,其中模型组大鼠粪便微生物具有较高的物种丰度和种群差异性。对门分类水平上的物种丰度分析发现,微生物种群主要由厚壁菌门(Firmicutes)和拟杆菌门(Bacteroidetes)组成;对属分类水平上的物种丰度分析发现,微生物种群由乳杆菌属(Lactobacillus)、Muribaculaceae、拟杆菌属(Bacteroides)、柯林斯菌属(Collinsella)、梭菌属(Clostridium)、罗姆布茨菌(Romboutsia)、劳特氏菌属(Blautia)和毛螺菌科NK4A136群(Lachnospiraceae NK4A136_group)等菌属组成,与空白对照组相比,模型组中Muribaculaceae和柯林斯菌属的丰度显著升高,乳杆菌属、梭菌属、罗姆布茨菌和毛螺菌科的丰度显著下降;叶酸组中Muribaculaceae、拟杆菌属、柯林斯菌属和劳特氏菌属的丰度显著升高,梭菌属、罗姆布茨菌和毛螺菌科的丰度显著下降。研究探索了叶酸干预调控高尿酸血症大鼠肠道微生物的变化,为治疗高尿酸血症提供参考。  相似文献   

3.
目的:探讨母体长期处于低硒状态下是否对子代哺乳期生长发育影响.方法:将正常成年雌性SD大鼠随机分为低硒实验组(SR)和正常对照组(NC),分别使用常硒和自制低硒饲料喂养,4周后,确定低硒动物模型建立成功后并分别进行合笼.从子代出生开始,通过记录两组子代大鼠哺乳期的各项生长发育指标并检测子代体内硒含量,探讨母体低硒对子代哺乳期生长发育的影响.结果:低硒实验组子代SD大鼠体长及体重均低于正常对照组,并且低硒实验组子代SD大鼠的死亡率较正常对照组高;低硒实验组子代SD大鼠肝脏、心脏、肾脏以及血液中的硒含量均明显低于正常对照组;低硒实验组子代SD大鼠的心脏、肝脏及肾脏重量,均低于正常对照组.结论:母体长期处于低硒状态下,将对子代哺乳期的生长发育造成严重影响.  相似文献   

4.
目的观察叶酸联合成体神经干细胞对创伤性脑损伤大鼠的治疗作用,探讨其可能作用机制。方法 120只Wistar大鼠随机分为6组,正常组,模型组,假手术组,叶酸注射组,成体神经干细胞移植组,成体神经干细胞移植+叶酸注射组。倒置显微镜下观察神经干细胞形态学变化;流式细胞仪检测神经干细胞表面标记物CD105、CD45、CD44、CD29的表达;免疫荧光法检测神经元特异性烯醇酶(NSE成熟神经元的特异性标志)、胶质纤维酸性蛋白(GFAP胶质细胞的标记物)的表达;平衡木实验检测大鼠运动协调与整和能力;Morris水迷宫实验测试各组大鼠的学习记忆能力;HE染色及Brdu免疫组化实验观察脑组织形态学变化;酶联免疫吸附试验检测大鼠脑组中脑源性神经生长因子(BDNF)、神经生长因子(NGF)的表达;蛋白质印迹法检测脑组织中凋亡相关蛋白BCL-2、Bax、Caspase-3的表达。结果分离所得细胞能在体外传代培养,流式细胞仪检测发现细胞阳性表达CD44、CD29,阴性表达CD105、CD45,细胞经胎牛血清诱导分化后能形成NSE或GFAP阳性细胞。实验表明,叶酸与成体神经干细胞干预创伤性脑损伤大鼠模型后能显著改善其行为学变化,减轻脑组织的炎症反应,恢复受损神经细胞,增加脑组织内BDNF、NGF的含量,上调BCL-2的表达,下调Bax、Caspase-3的表达。结论叶酸联合成体神经干细胞干预创伤性脑损伤大鼠能显著改善中枢神经功能,对维持神经元微环境稳态具有重要的作用。  相似文献   

5.
The activity of the blood-brain neutral amino acid transport system is increased in rats infused with ammonium salts or rendered hyperammonemic by a portacaval anastomosis. This effect may be due to a direct action of ammonia or to some metabolic consequence of high ammonia levels, such as increased brain glutamine synthesis. To test these possibilities we evaluated the kinetic parameters of blood-brain transport of leucine and phenylalanine in control rats, in rats after continuous 24 h infusion of ammonium salts (NH4+ = 2.5 mmol X kg-1 X h-1), and in rats treated with methionine sulfoximine, an inhibitor of glutamine synthetase, before infusion of ammonium salts. In ammonia-infused rats without methionine sulfoximine treatment, the KD and Vmax of phenylalanine transport were increased, respectively, about 170% and 80% compared to controls, whereas the Km and Vmax of leucine transport were increased, respectively, about 100% and 200%. Electron microscopy demonstrated marked swelling of astrocytic processes around brain capillaries of ammonia-infused rats; however, capillary permeability to horseradish peroxidase apparently was not increased by ammonia infusion. Administration of methionine sulfoximine before ammonia infusion inhibited glutamine synthesis and prevented the changes in transport of leucine and phenylalanine, but apparently did not reverse the perivascular swelling. These results suggest that the ammonia-induced increase in the activity of transport of large neutral amino acids across the blood-brain barrier requires glutamine synthesis in brain, and is not a direct effect of ammonia.  相似文献   

6.
目的:探讨叶酸-壳聚糖Prdx6 shRNA纳米粒对胃癌细胞生长的影响。方法:制备靶向性叶酸-壳聚糖Prdx6 shRNA纳米粒,原子力显微镜观察其形态,激光粒度分析仪测定纳米粒的粒径;倒置荧光显微镜观察叶酸-壳聚糖Prdx6 shRNA纳米粒的转染效率;采用蛋白质印迹法检测胃癌细胞Prdx6蛋白的表达变化;CCK8细胞增殖实验检测胃癌细胞的存活率。结果:1制备成功叶酸-壳聚糖Prdx6 shRNA向纳米粒。2荧光显微镜下观察靶向性叶酸-壳聚糖Prdx6 shRNA纳米粒转染胃癌细胞的效率明显高于非靶向纳米粒;胃癌细胞转染靶向组纳米粒后Prdx6蛋白的表达显著低于非靶向组。3与对照组相比,叶酸-壳聚糖Prdx6 shRNA纳米粒能够明显抑制胃癌细胞的增殖(P0.01)。结论:1叶酸-壳聚糖Prdx6 shRNA纳米粒可高效转染胃癌细胞。2转染叶酸-壳聚糖Prdx6 shRNA纳米粒后胃癌细胞的生长明显受抑制。  相似文献   

7.
目的:探讨氟西汀联合六味地黄丸对更年期综合征患者抑郁症状及血清孕激素、叶酸及5-羟色胺水平的影响。方法:收集在我院就诊或住院治疗的80例更年期综合征患者,随机分为实验组和对照组,每组40例。对照组患者给予盐酸氟西汀治疗,实验组患者在对照组基础上给予六味地黄丸治疗。观察并比较两组患者治疗前后血清孕激素、叶酸及5-羟色胺水平的变化以及汉密尔顿抑郁量表(HAMD)评分。结果:与治疗前相比,两组患者治疗后的孕激素、叶酸以及5-羟色胺水平均显著升高(P0.05),HAMD评分水平明显下降(P0.05);与对照组相比,实验组患者的孕激素、叶酸以及5-羟色胺水平较高(P0.05),HAMD评分水平较低(P0.05)。结论:氟西汀联合六味地黄丸能够显著升高更年期综合征患者血清孕激素、叶酸及5-羟色胺水平,改善更年期综合征症状。  相似文献   

8.
目的:观察高同型半胱氨酸对高血压大鼠心肌内质网应激相关因子GRP94、caspase12表达的影响,及依那普利叶酸片(简称依叶片)对其表达的干预作用。方法:30只雄性成年自发性高血压大鼠(SHR),随机分为对照组、模型组和依叶片组,每组10只。对照组给予普通颗粒饲料喂养同时给予双蒸水灌胃,模型组给予含3%蛋氨酸的颗粒饲料喂养同时给予双蒸水灌胃,依叶片组给予含3%蛋氨酸的颗粒饲料喂养同时给予依叶片粉剂20 mg/kg/d灌胃。实验第8周末,用颈动脉插管法测各组大鼠平均动脉压(MAP),同型半胱氨酸检测仪检测血清同型半胱氨酸(homocystein,Hcy)浓度,称取体质量、全心质量及左心室质量计算大鼠心肌肥厚指数HWI及LVEI,通过HE染色观察心肌细胞形态学改变,免疫组化检测大鼠心肌组织中GRP94及caspase12表达水平。结果:①大鼠血清Hcy水平的变化。对照组大鼠血清Hcy值在正常值范围。与对照组相比,模型组大鼠血清Hcy值显著增高(P0.01);与模型组相比,依叶片组大鼠血清Hcy值明显降低(P0.01)。②大鼠HWI、LVEI及MAP的变化。模型组大鼠的HWI及LVEI均明显高于对照组(P0.05);依叶片干预后大鼠的HWI及LVEI均明显降低(P0.05)。对照组与模型组大鼠的MAP均明显增高,但两组大鼠的MAP差异无统计学意义(P0.05);与模型组相比,依叶片干预后大鼠的MAP明显降低(P0.01)。③大鼠心肌细胞内质网应激(endoplasmic reticulum stress,ERS)相关因子GRP94及caspase12表达。对照组及模型组大鼠心肌细胞GRP94及caspase12表达均增高。与对照组相比,模型组大鼠心肌细胞GRP94、caspase12表达增高更为明显(P0.05)。依叶片干预后大鼠心肌细胞GRP94、caspase12表达明显降低(P0.05)。结论:高Hcy通过ERS途径使高血压大鼠左室肥厚程度加重;依叶片可有效降低血清Hcy及血压水平,抑制心肌细胞ERS,从而有效逆转左室肥厚,其对左室肥厚干预的分子机制为"H型"高血压的预防及治疗提供了新的理论依据。  相似文献   

9.
After the outbreak of acute renal failure associated with melamine‐contaminated pet food, melamine and melamine‐related compounds have become of great interest from a toxicologic perspective. We investigated the potential effects of melamine in combination with cyanuric acid (M + CA, 1:1) on pregnant dams and embryo‐fetal development in rats. M + CA was orally administered to pregnant rats from gestational days 6 through 19 at doses of 0, 3, 10, and 30 mg/kg/day of both melamine and cyanuric acid. Maternal toxicity of rats administered 30 mg/kg/day M + CA was manifested as increased incidences of clinical signs and death; gross pathologic findings; higher blood urea nitrogen and creatinine levels; lower body weight gain and food intake; decreased thymus weight; and increased heart, lung, and kidney weights. Histopathological examinations revealed an increase in the incidence of congestion, tubular necrosis/degeneration, crystals, casts, mineralization, inflammatory cells in tubules, tubular dilation, and atrophy of glomeruli in maternal kidneys, whereas fetal kidneys did not show any histopathological changes. Developmental toxicity included a decrease in fetal (28%) and placental weights and a delay in fetal ossification (n = 7). Increased incidence of gross and histopathological changes in the maternal kidney was also found in the middle dose group (n = 12). No treatment‐related maternal or developmental effects were observed in the low dose group (n = 12). Under these experimental conditions, M + CA is embryotoxic at an overt maternotoxic dose in rats and the no‐observed‐adverse‐effect level of M + CA is considered to be 3 mg/kg/day for pregnant dams and 10 mg/kg/day for embryo‐fetal development.  相似文献   

10.
局部灼伤对茉莉酸在蚕豆幼苗中运输和分配的影响   总被引:1,自引:1,他引:0  
用示踪技术研究了3H-JA (jasmonic acid)在双子叶植物蚕豆(Vicia faba L.)中的运输和分配规律以及局部灼伤对其运输与分配的影响.外源3H-JA 能够以高于4~5 cm*min-1的速率在蚕豆幼苗体内向上和向下运输.幼叶局部灼伤能提高3H-JA的向上运输能力,促进3H-JA向受伤部位的调运;增加3H-JA向成熟叶片下表皮的运输分配比率;阻止3H-JA从受伤部位的向外输出.据此推测,伤胁迫下JA的运输与分配的改变可能与植物体防御伤反应密切相关,并有可能参与了对气孔运动的调控.  相似文献   

11.
局部灼伤对茉莉酸在蚕豆幼苗中运输和分配的影响   总被引:3,自引:0,他引:3  
用示踪技术研究了3 H_JA (jasmonicacid)在双子叶植物蚕豆 (ViciafabaL .)中的运输和分配规律以及局部灼伤对其运输与分配的影响。外源3 H_JA能够以高于 4~ 5cm·min-1的速率在蚕豆幼苗体内向上和向下运输。幼叶局部灼伤能提高3 H_JA的向上运输能力 ,促进3 H_JA向受伤部位的调运 ;增加3 H_JA向成熟叶片下表皮的运输分配比率 ;阻止3 H_JA从受伤部位的向外输出。据此推测 ,伤胁迫下JA的运输与分配的改变可能与植物体防御伤反应密切相关 ,并有可能参与了对气孔运动的调控  相似文献   

12.
摘要 目的:研究高压氧联合叶酸治疗老年脑小血管病患者认知功能及血浆Hcy变化。方法:选取2019年1月~2020年6月我院收治的80例老年脑小血管病患者作为研究对象,随机将其分为两组,对照组50例,给予叶酸治疗,研究组30例,给予高压氧联合叶酸治疗,观察两组患者治疗后的疗效、认知功能、血浆Hcy水平、生活质量及不良反应。结果:治疗前,两组的蒙特利尔认知评估量表(Montreal Cognitive Assessment,MoCA)认知功能评分、血浆Hcy水平、日常生活能力量表(Activity of Daily Living Scale,ADL)评分对比无差异(P>0.05),治疗后两组的MoCA认知功能评分、ADL评分均升高,血浆Hcy水平均降低,且观察组变化优于对照组( P<0.05);治疗期间对照组不良反应发生情况为13.33 %,观察组不良反应发生情况为16.00 %,两组对比差异无统计学意义(P>0.05);研究组总有效率显著高于对照组(93.33 % vs.74.00 %,P<0.05)。结论:高压氧联合叶酸治疗老年脑小血管病患者疗效显著,能显著改善患者的认知功能和Hcy水平,提高其日常生活能力,且安全性高,值得临床应用。  相似文献   

13.
The expression of c-fos mRNA in rat brain was induced by intraperitoneal administration of pentylenetetrazole (PTZ) and picrotoxin, which act on the picrotoxin binding site of the gamma-aminobutyric acid-benzodiazepine (GABA-BZ) receptor complex, by N-methyl-D-aspartate (NMDA) and kainic acid, agonists of different classes of glutamate receptors and by caffeine, an antagonist of adenosine receptors. The actions of PTZ and picrotoxin but not that of NMDA were blocked by ethanol and the NMDA-receptor antagonist, MK-801. Ro 15-4513 partially reversed the inhibitory effect of ethanol on PTZ-induced c-fos mRNA synthesis. Acute ethanol administration blocked the actions of PTZ and NMDA without affecting the response to kainic acid or caffeine. Taken together, these data suggest that ethanol blocks c-fos gene activation by noncompetitive antagonists of the GABA-BZ receptor via actions on both the NMDA and GABA receptors.  相似文献   

14.
Calabrese  V.  Rizza  V. 《Neurochemical research》1999,24(1):79-84
A study was undertaken in rats to evaluate the effects of short-term oral ethanol administration on the levels of fatty acid ethyl esters (FAEE) in brain and peripheral organs in the presence and absence of pretreatment with L-carnitine. Administration of ethanol to rats for seven days resulted in fatty acid ethyl ester formation, particularly in the heart and brain, but also in the kidney and liver. FAEE generation was associated with a significant increase of GSH transferase activity. Treatment with L-carnitine significantly reduced both FAEE and GSH transferase activity, and these effects were associated with a significant decrease in alcohol blood concentrations. The present evidence supports the hypothesis that fatty acid ethyl esters could be mediators involved in the production of alcohol-dependent syndromes. Administration of L-carnitine through an increment in lipid metabolism and turnover, and by the modulation of cellular antioxidant enzymes, greatly reduces these metabolic abnormalities supporting its potential usefulness as a pharmacological tool in alcoholism management.I wish to dedicate this paper to the memory of Prof. Victor Rizza who tragically disappeared on the 2nd of September when this paper was in press  相似文献   

15.
In a cortical P2 fraction, [14C]gamma-aminobutyric acid ([14C]GABA), [14C]glycine, [14C]taurine, and [14C]glutamic and [14C]aspartic acids are transported by four separate high-affinity transport systems with L-glutamic acid and L-aspartic acid transported by a common system. GABA transport in cortical synaptosomal tissue occurs by one high-affinity system, with no second, low-affinity, transport system detectable. Only one high-affinity system is observed for the transport of aspartic/glutamic acids; as with GABA transport, no low-affinity transport is detectable. In the uptake of taurine and glycine (cerebral cortex and pons-medulla-spinal cord) both high- and low-affinity transport processes could be detected. The high-affinity GABA and high-affinity taurine transport classes exhibit some overlap, with the GABA transport system being more specific and having a much higher Vmax value. High-affinity GABA transport exhibits no overlap with either the high-affinity glycine or the high-affinity aspartic/glutamic acid transport class, and in fact they demonstrate somewhat negative correlations in inhibition profiles. The inhibition profiles of high-affinity cortical glycine transport and those of high-affinity cortical taurine and aspartic/glutamic acid transport also show no significant positive relationship. The inhibition profiles of high-affinity glycine transport in the cerebral cortex and in the pons-medulla-spinal cord show a significant positive correlation with each other; however, high-affinity glycine uptake in the pons-medulla-spinal cord is more specific than that in the cerebral cortex. The inhibition profile of high-affinity taurine transport exhibits a nonsignificant negative correlation with that of the aspartic/glutamic acid transport class.  相似文献   

16.
目的:对不同胃癌前病变中医证型和血清胃蛋白酶原(pepsinogen,PG)、胃泌素-17(gastrin-17,G-17)、癌胚抗原(carcinoembryonic antigen,CEA)和叶酸水平变化的关系进行探讨,为胃癌前病变的诊断提供一定的依据。方法:以80例胃癌前病变(precancerous lesion of gastric cancer,PLGC)患者研究组,80例健康者为对照组,对研究组患者进行中医临床辨证分型,对两组研究对象的血清PG、G-17、CEA和叶酸进行测定比较。结果:研究组PLGC患者中医证型分布不均匀,差异显著(P<0.05),由多到少依次为湿热蕴胃并/兼脾胃虚寒证>胃络瘀阻并/兼气阴两虚证>痰湿中阻并/兼脾胃气虚证>肝胃气滞并/兼气阴两虚证>肝胃气滞并/兼脾胃虚寒证>湿热蕴胃并/兼胃阴不足证。PLGC不同中医证型患者血清PG I和PG II水平差异显著(P<0.05);与对照组比较,各证型PG I水平均显著降低,PG II水平均显著升高(P<0.05)。且湿热蕴胃并/兼脾胃虚寒证和胃络瘀阻并/兼气阴两虚证的PG I水平显著低于其他证候,血清PG II水平显著高于其他(P<0.05)。与对照组比较,研究组不同证候的G-17、CEA水平显著升高,叶酸水平显著降低(P<0.05);观察组中湿热蕴胃并/兼脾胃虚寒证和胃络瘀阻并/兼气阴两虚证G-17、CEA显著高于其他证候,叶酸水平显著低于其他证候(P<0.05)。结论:胃癌前病变不同中医证型血清PG、G-17、CEA和叶酸存在明显差异。  相似文献   

17.
The steady-state brain/plasma distribution ratios of [14C]deoxyglucose ([14C]DG) for hypoglycemic rats previously determined by measurement of DG concentrations in neutralized acid extracts of freeze-blown brain and plasma exceeded those predicted by simulations of kinetics of the DG model. Overestimation of the true size of the precursor pool of [14C]DG for transport and phosphorylation could arise from sequestration of [14C]DG within brain compartments and/or instability of metabolites of [14C]DG and regeneration of free [14C]DG during the experimental period or extraction procedure. In the present study, the concentrations of [14C]DG and glucose were compared in samples of rat brain and plasma extracted in parallel with perchloric acid or 65% ethanol containing phosphate-buffered saline. The concentrations of both hexoses in acid extracts of brain were higher than those in ethanol, whereas hexose contents of plasma were not dependent on the extraction procedure. The magnitude of overestimation of DG content (about 1.2-to fourfold) varied with glucose level and was highest in extracts isolated from hypoglycemic rats; contamination of the [14C]DG fraction with 14C-labeled nonacidic metabolites also contributed to this overestimation. Glucose concentrations in acid extracts of brain exceeded those of the ethanol extracts by less than 40% for normal and hypoglycemic rats.  相似文献   

18.
对饭包草大粒种子萌发过程中胚结构变化、养分运输和肖耗的细胞学过程进行了观察.结果显示:种子萌发时萌发孔盖张开,胚根、胚芽、胚轴、子叶鞘和子叶柄突破种皮生长,子叶片呈球状留在胚乳内吸收营养;透射电镜观察显示胚乳养分运输主要通过传递细胞运输、穿壁运输、胞间通道运输三种方式;细胞内养分消耗过程是细胞程序性死亡的过程,多膜小体...  相似文献   

19.
Changes in the hepatic concentration of n-3 fatty acids, e.g., eicosapentaenoic acid and linolenic acid, were significantly reduced by their simultaneous administration with sesamin, whereas there was no such effect of sesamin for n-6 and n-9 fatty acids. However, there was no significant difference in lymphatic absorption between eicosapentaenoic acid (n-3) and arachidonic acid (n-6), irrespective of the presence or absence of sesamin.  相似文献   

20.
Sprague-Dawley rats were fed eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) ethyl esters at the 2% level for 3 weeks to clarify their effects on immune functions. In the rats fed EPA or DHA, serum cholesterol, triglyceride, and phospholipid (PL) levels were significantly lower than those in the rats fed safflower oil. In PL fractions of serum, liver, lung, splenocytes, and peritoneal exudate cells (PEC), increases in linoleic and dihomo-γ-linolenic acid contents and a decrease in arachidonic acid (AA) content were observed in the rats fed EPA or DHA. In addition, the EPA content increased in the rats fed EPA and DHA. In the rats fed EPA or DHA, a decrease of LTB4 productivity and an increase of LTB5 productivity were observed in the PEC, in response to the treatment with 5 μM calcium ionophore A23187 for 20 min. The changes in leukotriene production were more marked in EPA-fed rats than in DHA-fed rats. These results suggest that dietary EPA affects lipid metabolism and leukotriene synthesis more strongly than DHA.  相似文献   

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