阿魏酸对小鼠脑缺血再灌注损伤及大鼠血液流变性的影响

目的观察阿魏酸对小鼠脑缺血再灌注损伤、大鼠血液流变性的影响。方法用结扎双侧颈总动脉法,造成小鼠脑缺血再灌注模型;观察阿魏酸(0.8,1.6 g·kg^-1·d^-1)对小鼠全脑缺血30m in及再灌注60m in后超氧化物歧化酶(SOD)活性、乳酸脱氢酶(LDH)活性、MDA含量的影响。大鼠皮下注射肾上腺素(0.8mg·kg^-1),共2次,间隔4h,在第一次注射后2h将大鼠浸入4℃冰水5m in,造成血瘀模型,观察阿魏酸(50～200mg·kg^-1·d^-1)对血黏度的影响。结果阿魏酸(0.8g·kg^-1·d^-1)可显著提高脑组织LDH活性、可明显降低MDA含量、可显著提高SOD活性;阿魏酸(1.6g·kg^-1·d^-1)可显著降低MDA/SOD比值;对大鼠血黏度无明显影响。结论预防性应用阿魏酸对小鼠脑缺血再灌注损伤有一定程度的保护作用,对大鼠血液流变性无明显影响。     

葡萄籽原花青素抗大鼠脑缺血再灌注损伤的研究

目的:研究葡萄籽原花青素对大鼠脑缺血再灌注损伤的保护作用.方法:采用尼龙线栓塞大鼠大脑中动脉制备大鼠局灶性脑缺血再灌注模型,观察不同剂量的葡萄籽原花青素对脑梗死面积、脑组织含水量及血清中肌酸激酶(CK)、乳酸脱氢酶(LDH)和超氧化物歧化酶(SOD)活性的影响.结果:葡萄籽原花青素3、15、30 mg·kg-1可显著减小脑缺血再灌注损伤大鼠的行为评分,减轻缺血侧脑半球水肿程度,缩小脑梗死面积,显著降低血清中CK、LDH的活性,明显升高血清中SOD的活性.结论:葡萄籽原花青素对大鼠脑缺血再灌注损伤有保护作用,其升高血清SOD活性作用可能是其保护作用的机制之一.     

葛根素对大鼠脑缺血再灌注损伤的保护作用

目的观察葛根素对大鼠脑缺血再灌注损伤的保护作用。方法采用线栓法复制大鼠大脑中动脉脑缺血再灌注损伤模型,检测血液流变学指标,并测定再灌注后缺血侧脑组织含水量、丙二醛(MDA)含量、总抗氧化能力(T-AOC)和超氧化物歧化酶(SOD)活性。结果葛根素0.5、0.25、0.125 g.kg-1均可不同程度降低高、中、低切变率全血黏度、红细胞压积和血沉,降低缺血脑组织含水量和MDA含量,提高脑组织T-AOC,升高SOD活性。结论葛根素对大鼠大脑中动脉缺血再灌注损伤具有明显的保护作用。     

山茶花总黄酮对大鼠脑缺血再灌注损伤的保护作用

目的研究山茶花总黄酮(TFC)对大鼠全脑缺血再灌注损伤的保护作用。方法按pu lsinelli方法制成全脑缺血模型,大鼠全脑缺血30 m in后再灌注40 m in。记录脑缺血前、缺血30 m in及再灌注40 m in后的脑电图(EEG),取脑组织,采用荧光指示剂Fura-2定量测定大鼠前脑皮层组织细胞内游离钙离子浓度,测定超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、乳酸脱氢酶(LDH)、一氧化氮合酶(NOS)活性和丙二醛(MDA)、一氧化氮(NO)含量。结果TFC可促进缺血后EEG波幅的恢复,降低缺血再灌后细胞内游离钙离子浓度的升高,抑制SOD、GSH-Px和LDH活力的下降,降低NOS的活力和脑组织中MDA、NO的含量。结论TFC对脑缺血再灌注损伤有保护作用,其机制可能与其抗自由基、抑制钙超载和NO生成有关。     

姜黄提取物对脑缺血-再灌注大鼠一氧化氮及氧自由基的影响

目的探讨姜黄提取物对脑缺血-再灌注损伤保护作用的机制。方法将75只SD大鼠随机分为对照组、模型组和低、中、高剂量组。低、中、高剂量组分别给药姜黄提取物100mg·kg-1·d-1、200mg·kg-1·d-1、400mg·kg-1·d-1,对照组、模型组给等容量0.9%氯化钠溶液。每日灌胃1次,连用7d。用线栓法阻断大脑中动脉制备脑缺血-再灌注模型,观察大鼠神经损伤评分、测定脑组织丙二醛(MDA)、一氧化氮(NO)含量及超氧化物歧化酶(SOD)活性。结果模型组神经损伤评分显著高于对照组,差异有统计学意义(P<0.01);高、中、低剂量组神经损伤评分与模型组比较,差异有统计学意义(P<0.05)。模型组脑组织NO、MDA含量显著高于对照组;模型组脑组织SOD活性低于对照组,差异有统计学意义(P<0.01);高、中、低剂量组脑组织NO、MDA含量、SOD活性与模型组比较,差异有统计学意义(P<0.05)。结论姜黄提取物对脑缺血-再灌注损伤有保护作用,作用机制可能与提高脑组织SOD活性、降低脑组织MDA和NO含量有关。     

醋柳黄酮对大鼠脑缺血再灌注损伤的保护作用

目的:研究醋柳黄酮对大鼠脑缺血再灌注损伤的保护作用。方法:采用尼龙线栓塞大鼠大脑中动脉,制备大鼠局灶性脑缺血再灌注模型,观察不同剂量的醋柳黄酮对脑梗死面积、脑组织含水量及血清中肌酸激酶(CK)、乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)的活性和丙二醛(MDA)含量的影响。结果:醋柳黄酮3、15、30mg/kg可显著降低脑缺血再灌注损伤大鼠的行为评分,减轻缺血侧脑半球水肿程度,缩小脑梗死面积,显著降低血清中CK、LDH的活性及MDA含量,明显升高血清中SOD的活性。结论:醋柳黄酮对大鼠脑缺血再灌注损伤有保护作用,其抗脂质过氧化作用可能是其保护作用的机制之一。     

N-乙酰半胱氨酸和氯胺酮联用对脑缺血再灌注损伤的影响

目的:研究巯基供体物质N 乙酰半胱氨酸(NAC)和非竞争性NMDA受体拮抗剂氯胺酮(KT)联用对小鼠脑缺血再灌注损伤的影响。方法:雄性ICR小鼠,随机分为假手术组、生理盐水组(0 .0 1L·g- 1)、氯胺酮组(15mg·kg- 1)、N 乙酰半胱氨酸组(75mg·kg- 1)和联合组(KT 15mg·kg- 1 NAC75mg·kg- 1)。参照蒋晓帆等建立的方法,制备局灶性短暂性脑缺血再灌注模型(tMCAO) ,再灌注后6、2 4h测定神经行为缺陷评分,处死TTC染色测定脑梗死面积百分比;制备不完全性脑缺血再灌注模型(2 VO) ,在再灌注0 .5、2和6h时取全脑制成10 %匀浆,比色法测定MDA含量、SOD和GSH Px活力。结果:(1)短暂性局灶性脑缺血再灌注后6、2 4h ,各组小鼠脑组织均有不同程度梗死灶、神经行为缺陷明显,与生理盐水组比较,药物联合组可显著改善缺血再灌注小鼠的神经行为缺陷(均为P <0 .0 1) ,减少脑梗死面积百分比(均为P <0 .0 1) ,药物单用对以上指标有轻度的改善作用(P >0 .0 5 )。(2 )联合用药可明显改善脑细胞损伤。(3)与假手术组比较,不完全性全脑缺血再灌注损伤0 .5、2和6h后,生理盐水组小鼠MDA含量显著升高(均为P <0 .0 1) ,SOD活性(均为P <0 .0 1)和GSH Px活性均显著降低(均为P <0 .0 1)。与生理盐水组比较,联合组可显著地降低缺血再灌注小鼠脑组织     

注射用辛芍对大鼠脑缺血再灌注损伤的保护作用和对脑微循环血流量的影响

目的:观察注射用辛芍对大鼠中动脉阻断(MCAO)局灶性脑缺血再灌注损伤及脑缺血局部微循环血流量的影响。方法:采用栓线法建立局灶性脑缺血再灌注模型,观察注射用辛芍(0.31,0.62,1.25g.kg-1)分别对MCAO再灌注大鼠神经行为学、脑梗死率和脑组织超氧化物歧化酶(SOD)、一氧化氮合酶(NOS)活性,丙二醛(MDA)含量及脑组织病理变化的影响;使用相同动物模型,以激光多普勒血流仪监测各药物干预组对大鼠脑微循环血流的影响。结果:注射用辛芍可明显降低或改善MCAO大鼠行为障碍、脑梗死率及缺血所致组织病理改变,提高SOD活力,降低NOS活性及MDA含量,改善缺血大鼠脑微循环。结论:注射用辛芍对实验性脑缺血具有显著的保护作用,其作用机制可能与增强病灶组织抗氧化和改善局部脑微循环血流有关。     

1-(2,6-二甲基苯氧基)-2-(3,4-二甲氧基苯乙氨基)丙烷盐酸盐对小鼠脑缺血再灌损伤的保护作用

采用断颅 ,iv饱和MgCl2 溶液及结扎双侧颈总动脉和迷走神经等法造成小鼠脑缺血模型 ,观察 1 (2 ,6 二甲基苯氧基 ) 2 (3,4 二甲氧基苯乙氨基 )丙烷盐酸盐 (DDPH)对小鼠脑缺血后存活时间的影响 ;采用小鼠脑缺血 (2 0min)再灌注 (10min)模型 ,观察DDPH对脑组织超氧化物歧化酶 (SOD)活性 ,丙二醛 (MDA)含量及组织病理损伤的影响。结果显示 ,DDPH 3,6 ,12 ,2 4mg·kg- 1缺血前 30minip给药使小鼠存活时间明显延长 ;使小鼠脑缺血再灌注后脑组织内SOD活性增高 ,MDA含量下降 ,并明显改善神经细胞的病理性损伤 .结果提示DDPH对小鼠脑缺血再灌注所致损伤具有一定的保护作用     

QN胶囊对小鼠和大鼠脑缺血的保护作用

目的探讨QN胶囊对小鼠和大鼠脑缺血损伤的保护作用及机制。方法采用小鼠密闭缺氧实验,观察QN胶囊对小鼠存活时间的影响;结扎小鼠双侧颈总动脉及迷走神经造成急性脑缺血,观察QN胶囊对小鼠存活时间的影响;选用Wistar健康大白鼠,采用急性不完全性脑缺血再灌注模型,观察QN胶囊对大鼠脑含水量、脑指数、脑毛细血管通透性、组织形态学、脑组织中的超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH Px)、一氧化氮(NO)含量的影响。结果QN胶囊可延长缺氧小鼠和急性脑缺血小鼠的存活时间;可显著降低脑缺血再灌注模型大鼠的脑含水量、脑指数、脑毛细血管通透性及脑组织中的MDA和NO的含量;显著升高SOD和GSHPx的活性。结论QN胶囊对脑缺血及再灌注损伤有保护作用。     

Possible involvement of mast cells in collagen remodeling in the late phase of cutaneous wound healing in mice

We examined possible roles of mast cells in cutaneous wound healing using mast cell deficient (W/Wv) mice and their normal littermates (+/+). A round full-thickness wound was made on the back skin of these mice. The wounds closed completely within 20 days, and there was no difference in wound contraction between +/+ and W/Wv mice during the wound healing. While either chymase or tryptase activities were hardly detectable in W/Wv mice, chymase activities decreased at the impaired sites and recovered to the control level within 20 days in +/+ mice. Tryptase activities were higher than the control level on day 15 and day 20 in +/+ mice. Histological observations on day 15 and day 20 in +/+ mice revealed that mast cells were abundant at the wound edges but absent at the center. The latent and the active forms of MMP-2 and MMP-9 increased on day 10 and day 15 but recovered nearly to control levels on day 20 in both mice groups. The hydroxyproline contents in W/Wv mice were significantly higher than those in +/+ mice on day 15 and day 20. Furthermore, histological observations revealed that the collagen aggregation at the wound edges was tighter and less interwoven in W/Wv mice compared with +/+ mice. These results suggest that mast cells accumulated at the wound edge may participate in tissue remodeling in the late phase of wound healing.     

Intrastrain variations in anxiolytic effect of nitrazepam in mice

This study investigated the individual differences in the baseline anxiety and anxiolytic effect of nitrazepam in Balb/c mice. Initially mice were sorted according into low, intermediate and high anxiety groups (LA, IA and HA) based on the number of entries to and time spent in open arms in elevated plus maze. Later, anxiolytic effect of nitrazepam (2 mg/kg, p.o) in LA, IA and HA mice was evaluated using hole board and light/dark tests. In Hole board test, LA mice made more number of head dippings and spent more time during head dippings, while HA mice made less number of head dippings and spent less time during head dipping when compared to that of IA mice. In light/dark test LA mice made more reentries to and spent more time in bright compartment, while HA mice made few reentries to and spent less time in bright compartment. Results suggest that mice of a single strain differ in their baseline anxiety and anxiolytic effect of nitrazepam.     

Ethanol-induced changes in tyrosine hydroxylase activity in brains of mice selectively bred for differences in sensitivity to ethanol

The effects of ethanol on tyrosine hydroxylase (TH) activity in five brain areas were analyzed in two lines of mice selectively bred for their differences in sensitivity to ethanol. Following a 4.1 g/kg dose of ethanol, intraperitoneally, short sleep (SS) mice lose their righting reflex for a duration of 20 minutes and long sleep (LS) mice fail to regain their righting reflex until 120 minutes. A significant increase in TH activity occurred in the striatum, locus coeruleus and frontal cortex in both lines of mice approximately 25 minutes following ethanol administration. A decrease in TH activity occurred in the substantia nigra of SS mice at 5 minutes following ethanol administration. However, there was no significant difference in TH activity in any of these four brain regions between LS and SS mice at any time following ethanol administration. In contrast, hypothalamic TH activity was significantly increased at 25 minutes in the SS mice and at 125 minutes in the LS mice following the administration of ethanol, times which coincided with the regaining of the righting reflex. These data suggest that activation of TH in the hypothalamus of LS and SS mice in response to ethanol is associated with arousal from ethanol induced narcosis.     

The role of the catecholaminergic system in footshock-induced fighting in mice

The role of the catecholaminergic system in foot shock-induced fighting aggression in mice was studied with the help of behavioral tests and biochemical experiments. The administration of the catecholamine precursor l-dopa combined with enzymatic decomposition inhibitors (nialamide or Ro4-4602) produced a significant increase in the number of fighting episodes in mice. The administration of the dopamine agonists amantadine, apomorphine, and nomifensine also increased aggression in mice. Catecholamine synthesis inhibitors, alpha-MT and compounds blocking catecholamines receptors (pimozide and haloperidol), reduced the number of fighting epidoses in mice. Clonidine, a noradrenergic agonist, potentiated the aggressive behavior of mice while the noradrenergic antagonists aceperone and phenoxybenzamine, the alpha-adrenergic receptor blockers, suppressed aggression. The noradrenaline synthesis inhibitor FLA-63 also depressed the number of fighting episodes in mice. A comparison of two effective doses (ED₅₀) for antiaggressive action and for the inhibition of motor activity showed that alpha-MT, FLA-63, and aceperone reduced the number of fighting episodes in mice most selectively. The interaction between catecholamine agonists and antagonists showed that an increase of aggression induced by nialamide plus l-dopa was abolished both by haloperidol and by phenoxybenzamine. Clonidine effects were also partially weakened by phenoxybenzamine. Studies on noradrenaline and dopamine levels in the brains of mice, after the synthesis of those catecholamines was inhibited, showed a higher noradrenaline utilization in the brains of aggressive mice than in nonaggressive mice. The present results suggest a significant role of noradrenaline dopamine in producing the foot shock-induced fighting aggression in mice.     

Cell proliferation and apoptosis are altered in mice deficient in the NF-kappaB p50 subunit after treatment with the peroxisome proliferator ciprofibrate.

We previously showed that the peroxisome proliferator ciprofibrate increases hepatic NF-kappaB DNA binding activity in rats, mice, and hepatoma cell lines. Here, we analyzed the response to ciprofibrate in mice that lack the NF-kappaB p50 gene (p50-/-). Wild-type and p50-/- mice were fed a diet with or without 0.01% ciprofibrate for 10 days. NF-kappaB DNA binding activity was present and increased after ciprofibrate treatment in wild-type mice, but was not detected in p50-/- mice. The untreated p50-/- mice had a higher level of hepatic cell proliferation, as measured by BrdU labeling, than did untreated wild-type mice. However, the increase in proliferation was greater in ciprofibrate-fed wild-type mice than in ciprofibrate-fed p50-/- mice. The apoptotic index was low in wild-type mice in the presence or absence of ciprofibrate. Apoptosis was increased in untreated p50-/- mice compared to wild-type mice; apoptosis was reduced in p50-/- mice after ciprofibrate feeding. The c-Jun and JunB mRNA levels were higher in untreated p50-/- mice than in untreated control mice; c-Jun mRNA levels increased, whereas JunB mRNA levels decreased in both groups after ciprofibrate treatment. The c-Jun and JunB protein levels were the same in untreated wild-type and p50-/- mice and increased in both groups after ciprofibrate treatment. Several apoptosis-related mRNAs were higher in untreated p50-/- mice compared to untreated control mice; expression of these genes increased in both groups after ciprofibrate treatment. These data indicate that NF-kappaB contributes to the proliferative and apoptotic changes that occur in the liver in response to ciprofibrate.     

Strain differences in the reverse tolerance to methamphetamine and changes in catecholaminergic neurons in mice

The effect of methamphetamine (MAP) on ambulatory activity and neurochemical changes in catecholaminergic neurons in the brain were investigated in dd and C57BL/6 strains of male mice. The mice were given repeatedly MAP at 2 mg/kg, s.c., 10 times at a fixed interval of 4 days. Single MAP markedly increased the ambulatory activity in both strains of mice. The ambulation-increasing effect was progressively enhanced without accompanying stereotyped behaviors when the drug was repeatedly given. The dd mice showed higher susceptibility not only to single MAP but also to the enhancing effect of the drug (reverse tolerance) that the C57BL/6 mice. On the other hand, non-treated dd mice exhibited lower maximum densities of 3H-spiperone binding sites in the striatum and 3H-WB4101 binding sites in the cortex and hippocampus than non-treated C57BL/6 mice. In contrast, the dd mice exhibited higher noradrenaline turnover than the C57BL/6 mice in the brain regions examined. The repeated administration of MAP produced decrease in the densities of both 3H-spiperone and 3H-WB4101 binding sites in the corresponding regions with increase in catecholamine turnover in dd mice. However, the similar changes were observed only in 3H-WB4101 binding sites and noradrenaline turnover in C57BL/6 mice. These results suggest that the ambulation-increasing effect of MAP is positively correlated with catecholamine turnover, while it was correlated negatively with the densities of catecholamine binding sites. Furthermore, the enhancing effect of MAP is supposed to have been partially elicited by changes in brain catecholaminergic systems, in particular an increase in catecholamine turnover.(ABSTRACT TRUNCATED AT 250 WORDS)     

Naloxone-induced analgesia in diabetic mice

We evaluated the effects of s.c. administration of naloxone in mice with streptozotocin-induced diabetes, compared to those in age-matched naive mice. Naloxone injected s.c. produced a dose-related increase in tail-flick latency in diabetic mice but not in naive mice. Naloxone-induced analgesia in diabetic mice was significantly reduced by pretreatment with naltrindole, a selective antagonist of δ-opioid receptors. These results indicte that naloxone-induced ‘paradoxical’ analgesia in diabetic mice may be mediated by δ-opioid receptors.     

Effects of selective serotonin reuptake inhibitors on immobility time in the tail suspension test in streptozotocin-induced diabetic mice

We examined the effects of fluoxetine and fluvoxamine, selective serotonin reuptake inhibitors (SSRIs), and desipramine, a selective noradrenaline (NA) reuptake inhibitor, given alone or in combination with diazepam on immobility time in the tail suspension test in diabetic mice. Immobility time was significantly longer in diabetic than in nondiabetic mice. Diazepam (0.1 and 0.3 mg/kg s.c.) dose-dependently decreased immobility time in diabetic mice to the level observed in saline-treated nondiabetic mice. However, diazepam had no significant effect on immobility time in nondiabetic mice. Fluoxetine (3-56 mg/kg i.p.) and desipramine (1-30 mg/kg i.p.) produced marked, dose-dependent suppression of immobility time in both nondiabetic and diabetic mice. However, anti-immobility effects of fluoxetine and desipramine in diabetic mice were less than those in nondiabetic mice. Fluvoxamine (3-30 mg/kg i.p.) produced a dose-dependent suppression of immobility time in nondiabetic mice but not in diabetic mice. The anti-immobility effects of fluoxetine, fluvoxamine and desipramine in nondiabetic mice were antagonized by pretreatment with diazepam (0.3 mg/kg s.c.). Furthermore, fluoxetine, fluvoxamine and desipramine had no effect on the immobility time in diazepam (0.3 mg/kg s.c.)-treated diabetic mice. These results indicate that the anti-immobility effects of SSRIs and desipramine are less in diabetic mice than in nondiabetic mice in the tail suspension test. Furthermore, in diabetic mice, SSRIs and selective NA reuptake inhibitors did not affect immobility time even though the prolonged duration of immobility was suppressed by pretreatment with diazepam.     

解酒合剂作用研究

目的:探讨解酒合剂的作用。方法:观察和比较解酒合剂对小鼠的攀爬活动、翻正反射和睡眠的影响。结果:解酒合剂能明显缓解小鼠因醉酒引起的平衡失调现象,延长小鼠睡眠耐受时间,缩短睡眠维持时间,降低急性酒精中毒的死亡率。结论:解酒合剂具有良好的解酒作用。     

Increase in plasma fibrinogen and plasminogen activator inhibitor level in diabetic KK and KK-Ay mice

Coagulation activity in KK mice and KK-Ay mice produced by transferring the yellow obese gene (Ay) into KK mice, was studied to examine whether both mice are useful as a model of diabetic atherosclerosis. Plasma levels of hemoglobin A1c (HbA1c), insulin, fibrinogen, plasminogen activator inhibitor (PAI) and thrombomodulin were significantly high in KK and KK-Ay mice compared with age-matched non-diabetic mice (ddY mice). The changes in the plasma levels of fibrinogen at each time-point correlated with the increases in HbA1c levels. Pathological observation by Oil red O staining of aorta tissue from 4-month-old KK and KK-Ay mice revealed the early stages of atherosclerosis such as lipid deposition. These age-related increases in the plasma level of fibrinogen and PAI suggested that KK-Ay mice may contribute to help elucidate the early stages of diabetic atherosclerosis.