Utilization of dietary amino acids for energy production in neonatal rat liver.

The 3-day-old rat has a high basal level of phosphoenolpyruvate carboxykinase (PEPCK), the activity of which is not increased upon starvation. The lower basal activity of the enzyme in 19-day-old rat liver can, however, be stimulated by starvation. Serum glucose levels increased from 3 days to 19 days of age, with a decrease to adult levels. Liver glycogen concentration increased from 3 days to 19 days of age, with no additional increase observed at 3 months. There was a decrease with age in the specific activity of liver glycogen (from [14C]alanine and [14C]leucine). In fed rats given [14C]alanine, 14CO2 expiration tended to decrease with age. The 14CO2 production from [14C]leucine was less than that from alanine, and also decreased with age. Three-day-old rats showed no change in serum glucose when starved for 4 hr. On the other hand, 19-day-old rats responded with a decrease in serum glucose; although the adult animal's basal level of serum glucose was less than that of the 19-day-old rats, starvation for 15 hr also caused a significant decrease. There was no statistically significant difference in liver glycogen concentration between the fed and starved 3-day-old animals. Liver glycogen concentration in the 19-day-old adult rats was affected, however, by starvation. The 3-day-or glycogen during starvation. Starvation resulted in a tremendous increase in the specific activity of hepatic glycogen in the 19-day-old and adult rats. Starvation decreased the percentage of labeled amino acid expired as 14CO2. The proportion expired also decreased with age. Urinary nitrogen concentration increased significantly between 3 and 19 days of age. Starvation produced differential effects in the animals, with no change being observed in either the 3-day or adult rats; a decrease was observed in the 19-day-old animals. Urinary nitrogen concentration was measured in adult carbohydrate-deprived rats and was significantly higher than control values. These rats had a high gluconeogenic rate, reflected in the increased urinary nitrogen concentration. The young rat is at the mercy of a continuous supply of substrate in that it has a limited capacity for directing substrat     

发育期大鼠青霉素点燃后大脑皮质自噬标记蛋白LC-3表达及E-64d干预效应的研究

目的研究发育期大鼠反复惊厥后大脑皮层中自噬标记蛋白LC-3的表达,以及E-64d对其表达的影响。方法生后21 d的SD大鼠随机分成惊厥组、对照组、干预组3组,每组24只。惊厥组大鼠隔日腹腔注射青霉素(4.8×106U/kg),连续6次,诱导惊厥发作;对照组大鼠予同等剂量的生理盐水腹腔注射;干预组大鼠于腹腔注射青霉素诱导惊厥发作前,腹腔注射E-64d(4μg)。惊厥组和干预组大鼠于末次惊厥后3 h、12 h、24 h和出生51 d处死并取其大脑皮质,对照组大鼠也在相应时间点取大脑皮质。采用蛋白质免疫印迹技术(Western-blot)分别检测大鼠大脑皮质中自噬标记蛋白LC-3的表达。结果惊厥组大鼠于末次惊厥后3 h、12 h、24 h大脑皮层LC3II/LC3I较对照组升高,差异有统计学意义(t=2.091～10.353,P均<0.05);干预组与惊厥组大鼠比较,LC3II/LC3I降低,差异有统计学意义(t=2.911～5.980,P均<0.05)。在出生51 d时,三组大鼠间差异无统计学意义(P均>0.05)。结论大鼠惊厥急性期LC-3蛋白明显上调,自噬途径被激活,而E-64d参与了自噬途径的调控。     

戊四氮诱导发育鼠癫癎持续状态后海马神经发生及MK-801的影响

目的：探讨戊四氮诱导发育期大鼠癫癎持续状态(SE)后对海马内齿状回颗粒细胞神经发生的影响以及N-甲基D-天冬氨酸受体(NMDAR)拮抗剂MK-801对此结果的抑制作用,从而研究癫癎发作后发育脑海马内神经发生及NMDAR在神经发生中的作用。方法：SD大鼠7,14,21,28d4个日龄组共216只,每组均为54只,每个日龄组大鼠随机分SE组、MK-801组和正常对照组,每组18只。采用5-溴脱氧尿核苷(BrdU)标记新生细胞,再以β微管蛋白Ⅲ(TuJ1)、胶质原纤维酸性蛋白(GFAP)分别标记早期神经元和胶质细胞的单、双标免疫组织化学方法,检测PTZ诱导癫癎持续状态后发育鼠海马齿状回(dentategyrus,DG)神经发生,并用MK-801治疗后观察对其的影响。结果：BrdU注射后第7天和第14天,SE组各日龄幼鼠齿状回BrdU阳性细胞数明显高于同日龄的正常对照组,其中约有80%同时表达TuJ1;MK-801组BrdU阳性细胞数较SE组明显减少(P<0.01),而在第28天三组之间BrdU阳性细胞数无明显差异(P>0.05)。结论：癫癎发作可增加幼鼠齿状回颗粒细胞的神经发生,而NMDAR在癫癎后的神经发生中起着促进作用。     

新生鼠缺氧缺血性脑病蛋白激酶C与三磷酸肌醇及c-fos表达关系探讨

目的　对新生大鼠缺氧缺血性脑病 (HIE)第二信使蛋白激酶C(PKC)和 1,4 ,5 三磷酸肌醇 (IP3 )及c fos基因蛋白表达的关系进行研究。方法　生后 7d龄Wistar大鼠采用结扎右侧颈总动脉后放入含 5 %氧气和 95 %氮气的密闭容器 2 0min的方法制作HIE模型 ,分别于造模后 0 ,4 ,12 ,2 4 ,4 8,72h及 7,14 ,2 1d留取标本。对照组只做假手术 ,时间点与HIE组一致。PKC蛋白定量采用Lowry法 ,活性测定采用γ - 3 2 P催化活性测定法。IP3 测定采用放射受体竞争结合法 ,c fos基因蛋白表达采用免疫组织化学染色法。结果　与对照组比 ,HIE新生鼠脑皮质、海马神经细胞膜PKC活性降低 (P <0 .0 5或 0 .0 1) ,脑皮质神经细胞胞浆PKC活性升高 (P <0 .0 1) ,海马神经细胞胞浆PKC活性变化不大 ;动态观察PKC活性显示上述改变在造模后 72h内明显 ,并持续到 14d ,造模后 2 1d基本恢复正常。与此同时 ,脑皮质、海马神经细胞IP3 含量降低 ,丘脑IP3 含量升高 ,以上改变在 14d基本恢复正常。新生鼠HIE造模后即刻脑组织各部即有不同程度的c fos表达 ,且于缺氧缺血后 4h达高峰 ,以后强度逐渐降低 ,并持续至 72h。脑皮质c fos表达以Ⅱ -Ⅴ层明显 ,海马以CA1和DG区明显 ,CA3区也有表达 ,丘脑c fos表达稍有增加。结论　HIE诱导第二信使PKC及IP     

新生鼠缺氧缺血性脑病蛋白激酶C与三磷酸肌醇及c-fos表达关系探讨

目的：对新生大鼠缺氧缺血性脑病(HIE)第二信使蛋白激酶C(PKC)和1,4 ,5 三磷酸肌醇(IP3 )及c fos基因蛋白表达的关系进行研究。方法：生后7d龄Wistar大鼠采用结扎右侧颈总动脉后放入含5 %氧气和95 %氮气的密闭容器2 0min的方法制作HIE模型,分别于造模后0 ,4 ,12 ,2 4 ,4 8,72h及 7,14 ,2 1d留取标本。对照组只做假手术 ,时间点与HIE组一致。PKC蛋白定量采用Lowry法 ,活性测定采用γ - 3 2 P催化活性测定法。IP3 测定采用放射受体竞争结合法,c fos基因蛋白表达采用免疫组织化学染色法。结果：与对照组比 ,HIE新生鼠脑皮质、海马神经细胞膜PKC活性降低(P <0 .0 5或 0 .0 1) ,脑皮质神经细胞胞浆PKC活性升高 (P <0 .0 1) ,海马神经细胞胞浆PKC活性变化不大 ;动态观察PKC活性显示上述改变在造模后2h内明显,并持续到14d ,造模后 2 1d基本恢复正常。与此同时,脑皮质、海马神经细胞IP3 含量降低,丘脑IP3 含量升高,以上改变在 14d基本恢复正常。新生鼠HIE造模后即刻脑组织各部即有不同程度的c fos表达,且于缺氧缺血后4h达高峰,以后强度逐渐降低,并持续至72h。脑皮质c fos表达以Ⅱ -Ⅴ层明显,海马以CA1和DG区明显,CA3区也有表达,丘脑c fos表达稍有增加。结论：HIE诱导第二信使PKC及IP     

碱性成纤维细胞生长因子对癫(癎)持续状态大鼠海马谷氨酸和γ-氨基丁酸的影响

目的 通过戊四氮癫(癎)持续状态大鼠模型,观察碱性成纤维细胞生长因子(bFGF)对海马组织内主要的兴奋性氨基酸与抑制性氨基酸--谷氨酸和γ-氨基丁酸动态变化的影响.方法 建立60 d大鼠戊四氮(PTZ)诱导癫(癎)持续状态模型,生理盐水(NS)注射作为对照,皮下注射bFGF进行干预,分4组:即NS组、NS+bFGF组、PTZ组、PTZ+bFGF组.选择处理后第3、7、14天三个时间点进行观察,采用高效液相法检测海马组织谷氨酸和γ-氨基丁酸含量.结果 发作后3、7、14 d PTZ组海马组织谷氨酸较NS组有显著升高(P<0.01),以发作后14 d升高更为明显,PTZ+bFGF组各时间点谷氨酸较PTZ组下降(P<0.05);γ-氨基丁酸含量在PTZ组各时间点亦大于NS组(P<0.05),以发作后14 d升高较为显著;PTZ+bFGF组发作后各时间点γ-氨基丁酸较PTZ组差异无统计学意义(P>0.05).结论 大鼠癫(癎)持续状态后一定时间内海马谷氨酸和γ-氨基丁酸增加,bFGF能够降低大鼠癫(癎)发作后异常增加的谷氨酸含量.     

Development of gastric histidine decarboxylase in the rat: sensitivity to fasting and secretagogues

Gastric mucosal histidine decarboxylase (HDase) was measured in fetal rats between days 16 and 21 of gestation, and in newborn rats up to weaning. HDase was not detected in fetal stomach. Its activity developed from day 1 after birth (29 +/- 2 pmol CO2/mg protein/h) and increased up to day 18 when it reached the fed adult level (894 +/- 174 pmol CO2/mg protein/h). Weaning increased HDase activity significantly (weaned versus unweaned rats: 1,664 +/- 150 and 1,036 +/- 170 pmol CO2/mg protein/h; p less than 0.005). Up to day 18, HDase activity was not altered by 16 h to 24 h of fasting. From that day on, HDase became sensitive to both pentagastrin and carbachol. These results indicate that complete functional maturation of histamine-producing cells is only reached at day 18, just before weaning. This developmental pattern may explain the differences observed between fetal and adult regulation of gastric acid secretion.     

缺氧缺血新生大鼠脑组织caspase-1和白细胞介素18 mRNA表达及其关系探讨

目的研究caspase-1及其底物之一白细胞介素(IL)-18 mRNA的表达在缺氧缺血性脑损伤(HIBD)中的作用及其意义.方法 112只7日龄新生Wistar大鼠按照完全随机化方法分为对照组、HIBD 3、8、24 h、3、6和14 d组,每组16只.其中8只采用RT-PCR 方法检测caspase-1和IL-18 mRNA在HIBD后脑皮层中的表达及其相关性,另外8只光镜下观察脑组织病理学改变.结果对照组有caspase-1 mRNA少量表达(0.2918 ± 0.0809),HIBD 24 h组其水平开始增加(0.5222 ± 0.0941,与对照组比较P<0.01),6 d达高峰(0.7886 ± 0.0480,与其余各组相比P<0.01), 此后下降,但HIBD 14 d (0.5314 ± 0.1272)仍可检测出.对照组IL-18 mRNA水平为0.3218 ± 0.0466,HIBD 24 h至6 d其表达逐渐增加(24 h 0.5823 ± 0.0740; 3 d0.6976 ± 0.1073; 6 d 0.9110±0.0647,与对照组比较均为P<0.01),并达高峰(HIBD 6 d组与其余各组相比P<0.01).HIBD后IL-18 mRNA的表达在时间上与caspase-1具有紧密相关性(r=0.871,P<0.01).组织学检查发现神经元变性、坏死在HIBD 1～6天逐渐加重.结论 HIBD后caspase-1和IL-18 mRNA的表达逐渐增加,其变化规律与光镜观察到的脑损伤进展的时间框架吻合,提示它们均参与了新生鼠HIBD的病理形成过程.     

Treatment of experimental status epilepticus in immature rats: dissociation between anticonvulsant and antiepileptogenic effects

We studied the effects of treating status epilepticus (SE) induced by lithium and pilocarpine at postnatal day 15 (P15) or 28 (P28), on the severity of acute SE and of SE-induced epileptogenesis. Rats received topiramate (10 or 50 mg/kg, IP) or diazepam (5 mg/kg, IP) 20, 40 or 70 min after pilocarpine, and three months after SE 24-h video/EEG recordings were obtained for one (P28) or two weeks (P15) continuously. In P15 rats, topiramate did not modify the course of SE, yet treatment at 20 or 40 min completely prevented the development of spontaneous recurrent seizures (SRS) while later treatment (70 min) was partially effective in reducing the severity and frequency of SRS. Diazepam was effective against acute SE at all time points tested. Early (20 min) but not late treatment with diazepam had the effect of reducing the frequency and severity of SRS. In P28 rats, both drugs reduced the cumulative seizure time. Early treatment (20 min) with either drug reduced the incidence of chronic epilepsy. Late treatment (40/70 min) did not alter the incidence of SRS, but decreased their frequency. This study demonstrates that, in the treatment of SE, anticonvulsant and antiepileptogenic effects can be dissociated in a development-specific manner: topiramate was antiepileptogenic without being an effective anticonvulsant in P15 animals at the doses tested. Diazepam, on the other hand, was a better anticonvulsant than an antiepileptogenic agent in the P15 animals at the dose tested. Such effects were not seen in the older animals.     

Detrimental effects of the ketogenic diet on cognitive function in rats

The ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that is widely used to treat epilepsy in children. Although the KD has been shown to be efficacious in the treatment of childhood epilepsy, the long-term effects of the KD on brain development are not clear. The objective of this study was to examine the long-term effects of the KD on visual-spatial memory, activity level, and emotionality in immature rats after status epilepticus (SE). Weanling rats were subjected to lithium/pilocarpine-induced SE or saline injections and were then randomized to either the KD or regular rat diet, both fed ad libitum. One month later, rats were evaluated for visual-spatial memory in the water maze, activity level in the open field test, and emotionality with the handling test. Spontaneous recurrent seizures were measured using videotaping, and seizure susceptibility was tested with flurothyl inhalation. Brains were weighed and examined for mossy fiber sprouting and cell loss. Although rats treated with the KD were active and seemed healthy, their weight gain was substantially lower than that in rats that received regular rat diet. The KD reduced the number of spontaneous seizures but had no discernible effect on flurothyl seizure susceptibility. KD-fed rats, with or without SE, had significantly impaired visual-spatial learning and memory compared with rats that were fed regular diet. The KD had minimal effects on activity level and emotionality. Rats that were treated with the KD had significantly impaired brain growth. No differences in pathology scores between the KD and regular diet groups were seen after SE. Despite reducing the number of spontaneous seizures after SE, the KD resulted in severe impairment in visual-spatial memory and decreased brain growth, with no effect on mossy fiber sprouting. This study raises concerns about the long-term effects of the KD on brain development.     

Effect of tin protoporphyrin on the excretion rate of carbon monoxide in newborn rats after hematoma formation

This study evaluated the efficacy of tin protoporphyrin (TP), a competitive inhibitor of heme oxygenase, in suppressing the total body excretion rate of carbon monoxide (CO), an index of total bilirubin formation, in neonatal rats with artificially created hematomas. Wistar rat litters less than 12 h old were each divided into three groups of similar weight and treated as follows: (a) saline control (S); (b) hematoma, 80 microliter blood (H); (c) TP, 65 mumol/kg, and hematoma (TP-H). CO excretion of the H group increased rapidly after hematoma formation, reaching a maximum value of 79 +/- 4 SE microliter/kg/h 25 h later. Treatment with TP did not affect the pattern of CO excretion or its magnitude (78 +/- 2 SE microliter/kg/h, 25 h posthematoma). The S group showed no increase in CO excretion at this time (40 +/- 2 SE microliter/kg/h). At the conclusion of the experiment (45 h posthematoma), the plasma total bilirubin levels were slightly lower in the TP-H rats (1.0 +/- 0.1 SE mg/dl) than in H rats (1.2 +/- 0.1 SE mg/dl). The S rats had a plasma total bilirubin concentration of 0.8 +/- 0.1 SE mg/dl. The hepatic and splenic heme oxygenase activities were decreased by 61% (p less than 0.001) and 48% (p less than 0.05), respectively, in the TP-H rats as compared to the H rats. The S and H rats had similar enzyme activities. The results of this study suggest that though single-dose TP decreased tissue heme oxygenase activity, it did not significantly affect total bilirubin formation.     

洛沙坦对高氧致慢性肺疾病新生大鼠肺纤维化的影响

目的：血管紧张素II除了调节血压,还参与肺纤维化的发生。研究血管紧张素II 1型受体拮抗剂洛沙坦对高氧致慢性肺疾病（CLD）新生大鼠肺组织的影响,探讨洛沙坦在抗纤维化的作用及可能的机制。方法：将Waistar新生大鼠生后24 h内随机分为：空气组、高氧组、高氧+注射用水组、高氧+ 洛沙坦组,高氧组氧浓度为85%~90%,高氧+注射用水组、高氧+洛沙坦组在生后6 d每天用注射用水或洛沙坦(5 mg/kg)灌胃至实验结束,于7,14,21 d处死。观察病理组织学改变;生化检测肺组织超氧化物歧化酶活性(SOD)、丙二醛(MDA)和羟脯氨酸(HYP)的含量。结果：高氧暴露后大鼠肺泡数目减少,终末气腔扩张,次级隔数目减少,肺泡间隔显著增厚,甚至出现肺出血和肺实变。洛沙坦干预后肺泡间隔变薄,但肺泡腔没有明显缩小,且肺泡次级隔仍较少。高氧后14和21 d新生大鼠肺组织HYP含量较同期空气组显著增加(P<0.01),洛沙坦治疗2周后肺组织HYP含量较高氧组明显下降 (471.46±30.63 μg/kg vs 545.15±34.90 μg/kg, P<0.01); 高氧组在高氧暴露7 d时,SOD活力呈代偿性增加,之后逐渐下降至空气组水平;MDA水平在高氧暴露后显著增加,但随日龄增加呈下降趋势。洛沙坦治疗能增加高氧肺组织SOD的活力, 21 d时差异有显著性(82.94±4.62 U/mg protein vs 67.78±8.02 U/mg protein, P<0.01),同时降低MDA的水平(30.54±5.89 nmol/mg protein vs 48.75±8.09 nmol/mg protein, P<0.01)。结论：洛沙坦治疗能减轻高氧诱导新生鼠CLD肺纤维化的程度,该过程可能与肺组织抗氧化酶活性增加以及膜脂质过氧化减轻密切相关。［中国当代儿科杂志,2007,9（6）：591-594］     

癫癎发作对幼年大鼠海马齿状回神经发生影响的研究

目的 探讨癫癎发作对幼鼠齿状回颗粒细胞神经发生的影响。方法 生后第15天Wistar大鼠80只,随机分为癫癎组50只.对照组30只。癫癎组以海藻酸致癫,对照组幼鼠以相同方法注射生理盐水,2组于注射后第5天经腹腔注射5溴脱氧尿苷(BrdU)。采用BrdU标记新生细胞,再以β微管蛋白Ⅲ(βⅢtubulin,TuJ1)、钙调蛋白D28k(CaBP)和胶质原纤维酸性蛋白(GFAP)双标免疫组织化学方法分别标记早期神经元、成熟颗粒细胞和胶质细胞,观察致癫幼鼠齿状回颗粒细胞的神经发生。另外,采用Timm染色对P15致惊幼鼠于致惊后1及2个月的苔藓纤维发芽情况进行观察。结果 BrdU注射后第7天和第21天,癫癎组幼鼠齿状回BrdU阳性细胞数明显高于各自对照组(第7天:244±15与190±10;第21天:218±19与133±12,P均<0.05);BrdU注射后第7天,癫癎组和对照组幼鼠分别约80.2％和78.7％的BrdU阳性细胞同时表达TuJ1(p>0.05);:BrdU注射后第21天,癫癎组和对照组幼鼠分别约60.2％和58.2％的BrdU阳性细胞同时表达CaBP(P>0.05):BrdU注射后第7天和第21天,两组幼鼠均约3％-5％的BrdU阳性细胞同时表达GFAP。P15致惊幼鼠在致惊后1及2个月均未发现内分子层及CA3区苔藓纤维的发芽现象。结论 癫癎发作可增加幼鼠齿状回颗粒细胞的神经发生,这些新生细胞大多数从颗粒下层迁移     

新生大鼠缺氧缺血脑损伤后μ-calpain活化及其他相关因子表达变化的时程及意义

目的　探讨新生大鼠缺氧缺血性脑损伤 (HIBD)后脑内 μ calpain的活化、其他相关因子表达变化的时程及相互关系 ,进一步研究HIBD的发病机制。方法　HIBD模型采用改良的Rice法。应用Westernblot法半定量测定缺氧缺血 (HI)后 0、1、2、4、12和 2 4h大脑皮层和海马μ calpain、c Fos、c Jun、HSP70和HSP2 7的表达。蛋白浓度测定采用改良的Bradford法。结果　新生大鼠HI后 μ calpain裂解为 76和 80两个片段 ,两者比值在HI后显著提高 ,以海马更为明显 ,其中皮层在 2 4h、海马在 12h达到高峰。c Fos在HI后 2～ 12h海马显著高于皮层 (P <0 0 5 ) ,2 4h海马却低于皮层 (P <0 0 5 ) ;c Jun则 0～ 1h海马高于皮层 (P <0 0 5 ) ,4h以后皮层均高于海马 (P <0 0 5 ) (其中 12h差异无显著意义 )。c Fos和c Jun在HI后呈上升趋势 ,无论皮层或海马均在 2～ 4h达到高峰 ,以后渐下降 ,但 2 4h仍高于正常对照组。与对照组相比 ,c Fos在 1,2 ,4 ,12和 2 4h差异有显著意义 (P <0 0 5 ) ;c Jun在 0 ,1,2 ,4 ,12和 2 4h差异有显著意义 (P <0 0 5 )。HSP70在HI后 0h皮层显著高于海马 (P <0 0 5 ) ,1h海马显著高于皮层 (P <0 0 5 ) ,4h后皮层又均高于海马 (P <0 0 5 ) ;HSP2 7则HI后 1～ 2 4h海马均显著高于皮层 (P <0     

毛果芸香碱致慢性癫大鼠脑内药物转运体表达的变化

目的研究有机阴离子转运多肽亚型2(Oatp2)及P-糖蛋白(P-gp)在氯化锂-毛果芸香碱诱导的慢性癫大鼠脑组织中的表达。方法采用氯化锂-毛果芸香碱诱发Wistar大鼠慢性癫模型,免疫组织化学法检测其脑内Oatp2、P-gp的分布及表达情况。结果Oatp2及P-gp免疫反应阳性物质主要定位于脉络丛上皮细胞膜及脑血管内皮细胞膜,神经细胞膜也可见染色;性大鼠脑内Oatp2的表达低于正常大鼠(P<0.05);而P-gp的表达高于正常大鼠(P<0.05)。结论慢性癫大鼠脑内同时存在药物转运体Oatp2及P-gp的表达,两者表达变化相反。在癫病理过程中,Oatp2可能具有与P-gp不同的作用。     

新生大鼠反复惊厥对脑内γ-氨基丁酸B1受体表达的影响

目的：发育期脑损伤能通过改变神经递质受体表达造成脑功能长期障碍,该研究通过观察新生期反复惊厥对大鼠脑内γ-氨基丁酸(γ-aminobutyricacid,GABA)B1受体(GABAB1R)表达的影响及成年期记忆功能和惊厥阈的长期改变,探讨其间可能存在的相关性。方法：生后7d(P7)新生SD大鼠48只,随机分入惊厥组和对照组,每组24只,惊厥组仔鼠通过吸入三氟乙醚诱导惊厥,每天1次,连续6d。于反复惊厥结束后7d,每组各随机处死12只大鼠,应用RT-PCR及免疫组织化学方法检测大鼠大脑皮层及海马的GABAB1RmRNA及蛋白表达的近期改变。剩余大鼠于P61~P64行Morris水迷宫实验,检测大鼠的学习记忆功能。于P75时给予大鼠腹腔注射戊四唑测定大鼠的惊厥阈后,即刻处死大鼠取脑,用RT-PCR及免疫组织化学方法检测大鼠大脑皮层及海马的GABAB1RmRNA及蛋白表达的长期变化。结果：①在反复惊厥后7d及P75时,惊厥组大鼠大脑皮层中GABAB1RmRNA及蛋白的表达较对照组均显著下调(P<0.05);②惊厥结束后7d时,惊厥组大鼠海马区中GABAB1RmRNA表达较对照组无明显改变(P>0.05),但在齿状核GABAB1R蛋白表达明显降低(P<0.001);P75时惊厥组大鼠海马区GABAB1RmRNA及其在齿状核GABAB1R蛋白表达较对照组差异无显著性(P>0.05);③Morris水迷宫实验显示惊厥组大鼠在P64的寻找平台时间为98533.8±27205.4ms较正常对照组的46723.3±40666.5ms明显延长(t=3.66,P<0.05);④惊厥组大鼠注射戊四唑后发生惊厥的潜伏期为1415.1±428.5s与对照组1156.0±308.9s比较差异无显著性(t=1.70,P>0.05)。结论：新生期大鼠反复惊厥后,大脑皮层和海马GABAB1R表达持续减少,可能参与新生期惊厥后脑损伤的病理过程,与新生期反复惊厥导致的成年期记忆障碍相关。     

妥泰对宫内缺血Wistar大鼠海马星形胶质细胞及学习记忆能力的影响

目的 观察妥泰对宫内急性脑缺血损伤的Wistar大鼠海马星形胶质细胞及学习记忆能力的影响。方法 夹闭足月妊娠大鼠子宫血管,制成急性脑缺血损伤的新生鼠模型,治疗组给予妥泰,观察脑缺血后再灌注3h、6h、24h、3d、7d、14d、21d、28d海马GFAP标记的星形胶质细胞的变化,生后28d通过Morris全自动水迷宫实验,比较各组新生鼠学习记忆能力的差别。结果 妥泰治疗组新生鼠反应性星形胶质细胞在脑缺血再灌注早期的增生程度以及继之发生的大量减少的程度均较缺血对照组明显降低（P〈0．05）,多次给药组可以减少其晚期的过度增生（P〈0．05）,妥泰治疗组新生鼠学习记忆能力明显好于缺血对照组（P〈0．05）,且多次给药组学习记忆能力好于单次给药组（P〈0．05）。结论 妥泰可以明显减少宫内急性脑缺血后新牛大鼠星形胶质细胞的异常变化,改善急性脑缺血损伤的Wistar大鼠生后的学习记忆能力。     

Effect of respiratory acidosis on glucose homeostasis in experimental intrauterine growth retardation in rats

Hypoglycemia and asphyxia account for a significant proportion of morbidity in the infant with intrauterine growth retardation (IUGR). The purpose of this study was to evaluate changes in glucose homeostasis in IUGR rats during acute respiratory acidosis. IUGR was produced by bilateral uterine artery ligation at 17 days of gestation in 14 pregnant rats with 23 successfully delivered pups. The normal pups (n = 31) were those whose mothers were sham operated at the same gestational period. The IUGR and normal pups were studied at 2 days of age. One group of pups was studied under room air while another was subjected to 20 min of exposure to a gas mixture of 10% O2/15% CO2, balanced with N2. Gluconeogenesis in the liver and carcass, as well as plasma glucose and catecholamines were determined before and after the exposure to the gas mixture. The results showed that the 2-day-old IUGR rats have lower body weight (P less than 0.001), liver weight (P less than 0.001), plasma glucose (P less than 0.001), and rate of gluconeogenesis (P less than 0.01) when compared with the normally grown rats. During respiratory acidosis, the normally grown rats showed an increase in plasma epinephrine (P less than 0.005) without significant change in plasma glucose and rate of gluconeogenesis. The IUGR rats on the other hand, demonstrated a decrease in rate of gluconeogenesis (P less than 0.02), an increase in plasma glucose (P less than 0.001) while the plasma epinephrine level remained unchanged. We speculate that respiratory acidosis blunted cellular metabolism in the IUGR rat resulting in decreased peripheral glucose utilization.(ABSTRACT TRUNCATED AT 250 WORDS)     

r-HuEPO对癫癎持续状态大鼠血清NSE S-100β蛋白和MBP表达的影响

目的：通过观察重组人促红细胞生成素(r-HuEPO)对幼年大鼠癫癎持续状态（SE）后24 h血清神经元特异性烯醇化酶(NSE)、S-100β蛋白和髓鞘碱性蛋白(MBP)表达的影响,以观察其在癫癎性脑损伤中的可能作用。方法：40只19～21日龄Sprague-Dawley雄性大鼠随机分为正常对照组(CON组)、SE组、r-HuEPO预处理+SE组(SE-EPO组)、r-HuEPO组(EPO组)（n=10）,采用氯化锂 匹鲁卡品点燃制成SE模型。SE-EPO组和EPO组在制模前4 h腹腔注射r-HuEPO 500 IU/kg。在SE后24 h测定血清中NSE、S-100β蛋白、MBP含量的变化。结果：与CON、EPO组相比,SE组血清NSE、S-100β蛋白、MBP浓度均显著升高（P＜0.05）;与SE组比较,SE-EPO组NSE、S-100β蛋白、MBP均显著下降（P＜0.05）。结论：r-HuEPO可降低癫癎后神经组织损伤指标表达,对癫癎性脑损伤可能具有早期保护作用。     

毛果芸香碱致慢性癫癎大鼠脑内药物转运体表达的变化

目的 研究有机阴离子转运多肽亚型2（Oatp2）及P-糖蛋白（P-gp）在氯化锂-毛果芸香碱诱导的慢性癫癎大鼠脑组织中的表达。方法采用氯化锂-毛果芸香碱诱发Wistar大鼠慢性癫癎模型，免疫组织化学法检测其脑内Oatp2、P-gp的分布及表达情况。结果Oatp2及P-gp免疫反应阳性物质主要定位于脉络丛上皮细胞膜及脑血管内皮细胞膜，神经细胞膜也可见染色；癎性大鼠脑内0atp2的表达低于正常大鼠（P〈0．05）；而P-gp的表达高于正常大鼠（P〈0．05）。结论慢性癫癎大鼠脑内同时存在药物转运体Oatp2及P-gp的表达，两者表达变化相反。在癫癎病理过程中，Oatp2可能具有与P-gp不同的作用。