损毁大鼠双侧蓝斑引起多脏器出血

目的和方法：用直流电极毁大鼠双侧蓝斑,观察膀胱及各内脏组织的出血性变化。结果：完全损毁双侧蓝斑枷恒定地引起严重的膀胱出血,并伴有其它脏器不规律性发生的充血或轻微出血。部分损毁双侧蓝斑亦可引起多脏器轻微的充血和出血,但膀胱出血不再恒定发生。切除肾上腺减轻应激反应,或应用组织按H2受体拮抗剂,对完全损毁双侧蓝斑引起的膀胱出血或其它脏器的组织学出血性变化无明显影响。结论：损毁大鼠双侧蓝斑引起的多脏器出血并非由于手术应激引起;也与组织胺H2受 体无关,其机制有待进一步研究。     

Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain

To elucidate a role for the cytoskeletal protein actin in post-traumatic apoptotic cell death, the ability of actin-containing tissue extracts to inhibit exogenous DNase I was evaluated. In addition, cortical, hippocampal and thalamic extracts were examined for caspase-mediated actin cleavage and changes in actin polymerization state. Rats were anesthetized, subjected to lateral fluid percussion brain injury of moderate severity, and euthanized at 1 h, 6 h, 24 h, 1 week or 3 weeks post-injury (n = 3 per time-point). Tissue extracts from all brain regions of sham (uninjured) animals inhibited exogenous DNase I activity to a significant extent. However, inhibition of DNase I was significantly reduced at 1 h and 6 h in the injured hippocampus, and at 1 h, 6 h and 3 weeks in the thalamus. DNase I in cortical extracts of all injured animals was inhibited to a similar extent as that in uninjured animals. Actin fragments consistent with caspase-mediated proteolysis were observed in immunoblots of the injured hippocampus and thalamus at 1 h and 24 h, respectively, and were present up to 3 weeks post-injury. Transient actin hyperpolymerization was observed at 1 and 6 h post-injury in the thalamus and hippocampus, while actin depolymerization was observed at 1 and 3 weeks in the cortex and thalamus. Collectively our data suggest that DNase I disinhibition following brain trauma is associated predominantly with actin hyperpolymerization but also with actin depolymerization and concomitant caspase-mediated actin proteolysis.     

血管活性肠肽对清醒大鼠催乳素分泌的影响

在离体研究中发现,血管活性肠肽（ＶＩＰ）对催乳素分泌的促进作用因垂体所取自的动物模型的不同而异。本实验则以不同生理状态的大鼠为动物模型,于清醒自由活动状态下,检验ＶＩＰ的静脉注入对催乳素释放的影响。结果表明,在ＶＩＰ注入后１０ｍｉｎ时,其外周血液的浓度达到最高值（２１３２±２３３）ｎｇ／ｍｌ,并至少持续３０ｍｉｎ。在本实验的所有动物模型中,ＶＩＰ均诱导出了显著的催乳素分泌峰（Ｐ＜００５）,就其提高程度而言,雄性鼠最高（１５８０４±３７０６）ｎｇ／ｍｌ,未经吸吮刺激的哺乳母鼠最低（３１０５±４４２）ｎｇ／ｍｌ,而经过吸吮刺激的哺乳母鼠则居于两者之间（９０１０±３６００）ｎｇ／ｍｌ。ＶＩＰ在不同动物模型中所表现出的这些差异,提示其作用方式和／或作用部位可能受到整个机体内分泌环境和神经刺激的整合。     

Lactic acid bacteria: inhibition of angiotensin converting enzyme in vitro and in vivo

A total of 26 strains of wild-type lactic acid bacteria, mainly belonging to Lactococcus lactis and Lactobacillus helveticus, were assayed in vitro for their ability to produce a milk fermentate with inhibitory activity towards angiotensin converting enzyme (ACE). It was clear that the test strains in this study, in general, produce inhibitory substances in varying amounts. Using a spectrophotometric assay based on amino group derivatization with ortho-phthaldialdehyde as a measure of relative peptide content, it was shown that there is a significant correlation between peptide formation and ACE inhibition, indicating that peptide measurement constitutes a convenient selection method. The effect of active fermentates on in vivo ACE activity was demonstrated in normotensive rats. The pressor effect of angiotensin I (0.3 μg/kg) upon intravenous injection was significantly lower when rats were pre-fed with milks fermented using two strains of Lactobacillus helveticus. An increased response to bradykinin (10 μg/kg, intravenously injected) was observed using one of these fermented milks. It is concluded that Lactobacillus helveticus produces substances which in vivo can give rise to an inhibition of ACE. The inhibition in vivo was low compared to what can be achieved with classical ACE inhibitors. The clinical relevance of this finding is discussed. This work is the first in which an effect of fermented milk on ACE in vivo has been demonstrated, measured as decreased ability to convert angiotensin I to angiotensin II. This revised version was published online in June 2006 with corrections to the Cover Date.     

Amount of Bleeding and Hematoma Size in the Collagenase-Induced Intracerebral Hemorrhage Rat Model

The aggravated risk on intracerebral hemorrhage (ICH) with drugs used for stroke patients should be estimated carefully. We therefore established sensitive quantification methods and provided a rat ICH model for detection of ICH deterioration. In ICH intrastriatally induced by 0.014-unit, 0.070-unit, and 0.350-unit collagenase, the amount of bleeding was measured using a hemoglobin assay developed in the present study and was compared with the morphologically determined hematoma volume. The blood amounts and hematoma volumes were significantly correlated, and the hematoma induced by 0.014-unit collagenase was adequate to detect ICH deterioration. In ICH induction using 0.014-unit collagenase, heparin enhanced the hematoma volume 3.4-fold over that seen in control ICH animals and the bleeding 7.6-fold. Data suggest that this sensitive hemoglobin assay is useful for ICH detection, and that a model with a small ICH induced with a low-dose collagenase should be used for evaluation of drugs that may affect ICH.     

组织学与核磁共振检测大鼠癫痫源性早期脑损伤的跨半球扩布特征

侵性强直电刺激(60Hz,2s)大鼠右侧背海马(hippocampus,DHPC)CAl基树突区,1次/d,连续刺激10d。分别在施加强直电刺激的第2、4、6、8或10d时进行核磁共振成像检测(T2 weighted magnetic resonamce image T2-WI),并对鼠脑进行组织学切片鉴定。结果表明,早期慢性癫痫源性脑损伤的病理性形态特征主要包括：(1)T2-WI检测侧脑室(lateral ventricle,LV)区域信号增强、组织学检测LV扩大和双侧对称性脉络膜丛病理性增生,后两者并非完全平行呈现。(2)组织学切片显示双侧LV扩大面积与T2-WI信号增强区域面积的脑区分布近似。与空白对照组大鼠相比,电刺激2、4、6、8和10d后,T2-WI信号增强区域面积显著增大(P=0．0259;P＝0．0184;P=0．0184;P＝0．0404;P＝0．0259)以及组织学鉴定LV面积增大(P＝0．0210;P＝0．01;P＝0．0100;P=0．0152).(3)定侧分析显示,T2-WI信号增强以及T2-WI信号增强区域面积和组织学鉴定LV面积扩大,在慢性刺激6d时均以植入电极的对侧为主;第10d时均以同侧为主。三项观察结果的一致性证实了癫痫源性早期脑损伤的跨半球动态扩布特征。     

海马长时程增强与26S蛋白酶复合体活性变化的关系

实验观察了大鼠海马脑片上突触传递长时程增强(long term potentiation,LTP)的产生和维持中26S蛋白酶复合体活性的动态变化过程,初步分析了介导其变化的受体途径。结果显示:强直刺激前,26S蛋白酶复合体活性为190±14.3 cpm/(100 μg·2 h),强直刺激诱导fEPSP斜率增加10 min时,其活性升为273±18.3 epm/(100μg·2 h),强直刺激诱导fEPSP斜率增加60 min时,26S蛋白酶复合体活性又降为210±12.8 cpm/(100μg·2 h)。NMDA受体特异阻断剂AP-5在损害L1P产生的同时,抑制26S蛋白酶复合体活性升高。实验结果提示:大鼠海马LTP产生过程中,26S蛋白酶复合体活性存在一个短时间的,依赖于N-methyl-D-aspartate(NMDA)受体的升高过程。     

The influence of sodium metavanadate on the process of diabetogenesis in BB rats

Vanadium has been shown to be beneficial in the oral treatment of animal models of type 1 and type 2 diabetes. The aim of the study was to evaluate the short-term effects of sodium metavanadate in prediabetic BB-DP rats. To do this, 96 rats were divided into 4 equal groups. Groups VI, V2, V3 were treated with sodium metavanadate (0.1, 0.2 and 0.3 mg/ml respectively) and sodium chloride (0.5 mg/ml) in drinking water for 7 days. Group C received only sodium chloride (0.5 mg/ml). Blood glucose (BG), glycosuria, ketonuria, body weight and insulinemia were determined. The age of onset of diabetes was significantly higher for groups V2, V3 compared to group C, (p < 0.05) and depends on the metavanadate concentration (V3 vs. V1, p=0.006). The incidence of diabetes was lower in the rats treated with metavanadate than in the control group, but this difference was not statistically significant. In diabetic rats, the BG at the onset was higher in group C than in groups V, p < 0.05. Insulinemia, at the onset of the treatment as well as immediately after its cessation showed a drop in the treatment groups, proportionally to the dosage of vanadium, but later increased slowly and continuously until the end of the experiment. In conclusion, metavanadate delays the development of diabetes in BB-DP rats, but does not prevent its onset. A milder form of diabetes occurs in diabetic rats treated with metavanadate. The effects depend on the metavanadate concentration and 0.2 mg/ml is preferable.     

Comparison between D-[3-3H]- and D-[5-3H]glucose and fructose utilization in pancreatic islets from control and hereditarily diabetic rats

The metabolism of D-glucose and/or D-fructose was investigated in pancreatic islets from control rats and hereditarily diabetic GK rats. In the case of both D-glucose and D-fructose metabolism, a preferential alteration of oxidative events was observed in islets from GK rats. The generation of 3HOH from D-[5-3H]glucose (or D-[5-3H]fructose) exceeded that from D-[3-3H]glucose (or D-[3-3H]fructose) in both control and GK rats. This difference, which is possibly attributable to a partial escape from glycolysis of tritiated dihydroxyacetone phosphate, was accentuated whenever the rate of glycolysis was decreased, e.g., in the absence of extracellular Ca(2+) or presence of exogenous D-glyceraldehyde. D-Mannoheptulose, which inhibited D-glucose metabolism, exerted only limited effects upon D-fructose metabolism. In the presence of both hexoses, the paired ratio between D-[U-14C]fructose oxidation and D-[3-3H]fructose or D-[5-3H]fructose utilization was considerably increased, this being probably attributable, in part at least, to a preferential stimulation by the aldohexose of mitochondrial oxidative events. Moreover, this coincided with the fact that D-mannoheptulose now severely inhibited the catabolism of D-[5-3H]fructose and D-[U-14C]fructose. The latter situation is consistent with both the knowledge that D-glucose augments D-fructose phosphorylation by glucokinase and the findings that D-mannoheptulose, which fails to affect D-fructose phosphorylation by fructokinase, inhibits the phosphorylation of D-fructose by glucokinase.     

Dietary low linolenic acid compared with docosahexaenoic acid alter synaptic plasma membrane phospholipid fatty acid composition and sodium-potassium ATPase kinetics in developing rats

The objective of this study was to investigate if maternal dietary 20:4n-6 arachidonic acid (AA) and 22:6n-3 compared with adequate or low levels of 18:3n-3 linolenic acid (LNA) increases synaptic plasma membrane (SPM) cholesterol and phospholipid content, phospholipid 20:4n-6 and 22:6n-3 content, and Na,K-ATPase kinetics in rat pups at two and five weeks of age. At parturition, Sprague-Dawley rats were fed semi-purified diets containing either AA + docosahexaenoic acid (DHA), adequate LNA (control; 18:2n-6 : 18:3n-3 ratio of 7.1 : 1) or low LNA (18:2n-6 : 18:3n-39 ratio of 835 : 1). During the first two weeks of life, the rat pups received only their dams' milk. After weaning, pups received the same diet as their respective dams to five weeks of age. No significant difference was observed among rat pups fed the diet treatments for SPM cholesterol or total and individual phospholipid content at two and five weeks of age. Fatty acid analysis revealed that maternal dietary AA + DHA, compared with feeding the dams the control diet or the low LNA diet, increased 20:4n-6 in phosphatidylserine and 22:6n-3 content of SPM phospholipids. Rats fed dietary AA + DHA or the control diet exhibited a significantly increased Vmax for SPM Na,K-ATPase. Diet treatment did not alter the Km (affinity) of SPM Na,K-ATPase in rat pups at two and five weeks of age. It is concluded that dietary AA + DHA does not alter SPM cholesterol and phospholipid content but increases the 22:6n-3 content of SPM phospholipids modulating activity of Na,K-ATPase.