Therapeutic Effect of Neuronal Nitric Oxide Synthase Inhibitor (7-Nitroindazole) against MPTP Neurotoxicity in Mice

Effects of neuronal nitric oxide synthase (nNOS) inhibitor (7-nitroindazole), nonselective NOS inhibitor (N^G-nitro-L-arginine methyl ester; L-NAME), and monoamine oxidase inhibitor (pargyline) were studied on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. The mice received four intraperitoneal injections of MPTP at 1-h intervals. A significant depletion in dopamine and DOPAC concentration was observed in the striatum from 1 day after MPTP treatment. The pretreatment of 7-nitroindazole and pargyline, but not L-NAME, dose-dependently protected against MPTP-induced depletion in dopamine content 3 days after MPTP treatment. Our histochemical study also showed that 7-nitroindazole and pargyline can prevent a marked decrease in the nigral cells and a marked increase in astrocytes in striatum 7 days after MPTP treatment. The protective effect of 7-nitroindazole against MPTP-induced dopamine and DOPAC depletion in the striatum was not attenuated by intraperitoneal pretreatment with L-arginine. Furthermore, the posttreatment of 7-nitroindazole or pargyline protected against MPTP-induced depletion of dopamine content. These results demonstrate that the protective mechanism by which 7-nitroindazole counteracts MPTP neurotoxicity in mice may be due not only to inhibition of nNOS, but also to MAO-B inhibition. Furthermore, our study suggests that the posttreatment of 7-nitroindazole and pargyline can prevent a significant decrease in dopamine levels in the striatum of MPTP-treated mice. These findings have important implications for the therapeutic time window and choice of nNOS or MAO inhibitors in patients with Parkinson's disease.     

Inhibitory Effect of Dopamine on Gastric Motility in Rats

Background: There is disagreement with regard to the involvement of dopamine (DA) receptors in gastric motility. The mechanism of the inhibitory effect of DA on rat gastric motility was investigated in association with acetylcholine (Ach) release in the present study.

Methods: In vivo vagotomized, splanchnicectomized rats and control rats were used, and gastric movement was determined as the gastric motility index after DA administration. In vitro study of Ach release from the circular muscle strips of the gastric corpus was investigated after administration of domperidone, SCH23390, phentolamine, or propranolol.

Results: In the in vivo study DA inhibited gastric motility in a dose-dependent manner. Vagotomy and splanchnicectomy had no effect on the inhibitory effect of DA. In the in vitro study DA inhibited [³H]-Ach release in a dose-dependent manner. The inhibitory effect of DA was antagonized by domperidone but not by phentolamine, propranolol, or SCH23390.

Conclusions: Inhibition of gastric motility by dopamine is independent of extrinsic innervation and seems to be mediated by DA₂ receptors in the gastric wall.     

Effects of Ethanol and Temperature on NMDA Receptor Function in Different Mouse Genotypes

The present study investigated whether temperature-related changes in NMDA receptor sensitivity to ethanol might play a role in mediating the effects of body temperature on behavioral sensitivity to ethanol or in determining genotypic differences in sensitivity to ethanol. We accomplished this by determining the effects of ethanol on three different mouse genotypes (C57, LS, and SS) on two types of NMDA receptor-mediated responses at 30° and 35°C (i) extracellularly recorded synaptic potentials elicited in the CA1 region of the in vitro hippocampal slice preparation by stimulation of the Schaffer-commisural pathway in the presence of the cu-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor blocker, 6,7-dinitroqui-noxaline-2,3-dione, and low magnesium concentration; and (ii) increase in [³H]MK-801 binding elicited by glutamate in telencephalic membrane preparations. Ethanol significantly decreased NMDA receptor-mediated excitatory postsynaptic potential (EPSP) amplitude and area in the three genotypes. In C57, the effect of ethanol on NMDA receptor-mediated EPSP amplitude and area was more pronounced at 30°C, compared with that at 35°C. In most cases, there was a good correlation between the effects of ethanol on EPSP amplitude and area. The order of sensitivity between the three genotypes was C57 = LS > SS at 35°C and C57 > LS = SS at 30°C. Similarly, ethanol significantly decreased glutamate-stimulated [³H]MK-801 binding in membrane fractions. The effect of ethanol was temperature-dependent, because ethanol produced more inhibition at 30°C than at 35°C in all genotypes. The effect of ethanol on MK-801 binding was concentration-dependent, and the sensitivity to 100 mM ethanol of the genotypes at 35°C was LS > SS = C57, whereas it was SS > LS = C57 at 30°C. Collectively, the results demonstrate that temperature is an important variable that can influence NMDA receptor sensitivity to ethanol measured via electro-physiological and binding techniques, and that temperature can influence relative sensitivity of NMDA receptors to ethanol between mouse genotypes. Furthermore, the findings indicate that temperature-induced changes in sensitivity of NMDA receptors to ethanol may play a role in mediating the effects of body temperature on behavioral sensitivity to ethanol in LS, but not C57 and SS mice.     

Effect of glutamate receptor antagonists on suckling-induced prolactin release in rats

The aim of the present study was to investigate the role of endogenous excitatory amino acid receptors in suckling-induced prolactin (PRL) elevation. Glutamate is known to be the dominant excitatory neurotransmitter and may act simultaneously on different glutamatergic receptor subtypes. MK-801 (dizocilpine) is a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA), while GyKl 52466 is an antagonist of the R,S-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor subtypes. Using the combination of the two receptorsubtype antagonists, we tested the hypothesis that parallel blockade of more than one subtype is more effective. Low-dose MK-801 (0.033 mg/kg) had no effect on suckling-induced PRL elevation after 4 h of separation. When injected alone, 10 mg/kg of GyKl 52466 was also ineffective, but in combination with low-dose MK-801 it efficiently diminished the suckling-induced PRL elevation while lactation proceeded. The same dose of GyKl 52466 combined with 0.2 mg/kg of MK-801 (a combination that in other studies was able to block the foot-shock-induced PRL elevation) was more effective. Simultaneous blockade of the two ionotropic glutamate receptors with 0.2 mg/kg of MK-801 and 10 mg/kg of GyKl 52466 caused a decline in plasma PRL concentration of continuously suckling mothers. We conclude that the endogenous glutamatergic system has an important role in suckling-induced PRL elevation and in the maintenance of constantly high PRL levels in lactating mothers. Furthermore, the NMDA and AMPA/kainate receptor subtypes can interact with each other in this process.     

Effect of Acute Alcohol Withdrawal on Sensitivity to Pro-and Anticonvulsant Treatments in WSP Mice

Through the genetic technique of selective breeding, a mouse line [Withdrawal Seizure Prone (WSP)] has been developed that expresses severe handling-induced convulsions (HIC) after cessation of chronic ethanol exposure. These mice also display rebound elevations in HIC after a single ethanol injection. In the current studies, we tested WSP mice in several paradigms. WSP mice were found to be marginally sensitive to the effects of acute doses of dizocilpine to reduce HIC. However, when tested during acute withdrawal from a single ethanol injection, WSP were more sensitive to this compound. Although N-methyl- d -aspartate significantly elevated HIC in naive WSP mice, it was more effective at low doses when given during acute withdrawal. Withdrawing mice were slightly more sensitive than naive mice to kainic acid. Pentylenetetrazole elevated HIC in naive and withdrawing mice; it was marginally more effective in naive mice. Diazepam inhibited HIC in both naive and withdrawing mice, and was slightly more effective during acute withdrawal. This pattern of results suggests that acute alcohol withdrawal is accompanied by altered sensitivity to convulsants and anticonvulsants. These changes include enhanced sensitivity in at least two excitatory amino acid-gated ion channel binding sites.     

Effects of Ethanol, Chlordiazepoxide, and MK-801 on Performance in the Elevated-Plus Maze and on Locomotor Activity

The effects of ethanol, chlordiazepoxide, and MK-801 on performance in the elevated-plus maze and on activity measured in a circular activity monitor were compared in Sprague-Dawley rats to determine whether these effects of ethanol could be explained by its action on either GABA_A or NMDA receptors. Both ethanol and chlordiarepoxide produced an increase in the time spent in the open arms of the elevated-plus maze and in the ratio of open arm to total arm entries, indicative of an anxiolytic action of these drugs. MK-801 did not alter either the time spent in the open arms or the ratio of open to total arm entries. Chlordiazepoxide and MK-801 produced an increase in total arm entries that suggested that these compounds were increasing locomotor activity. Ethanol also increased total arm entries, but the effect was not statistically reliable. Following habituation to an activity monitor, neither ethanol nor chlordiazepoxide increased activity in this task, whereas MK-801 produced a robust increase in locomotion. Additionally, neither ethanol nor chlordiazepoxide blocked the MK-801-induced locomotor stimulation. The latter finding suggests that the effects of ethanol on GABAA receptors was not Mocking an increased activity level produced by its antagonism of NMDA. Additionally, these results indicate that the anxiolytic and locomotor action of ethanol in rats parallel the effects of a benzodiazepine and not those of an NMDA antagonist. Finally, these results suggest that the consequence of ethanol's antagonism of NMDA receptor function is more restricted than that produced by MK-801.     

Differences in NMDA Receptor Antagonist-Induced Locomotor Activity and [3H]MK-801 Binding Sites in Short-Sleep and Long-Sleep Mice

Short-Sleep (SS) and Long-Sleep (LS) mice differ in initial sensitivity to ethanol. Ethanol acts as an antagonist at N-methyl d -aspartate receptors (NMDARs). Therefore, we tested whether SS and LS mice also differ in initial sensitivity to NMDAR antagonists. Systemic injection (intraperitoneal) of either the noncompetitive NMDAR antagonist MK-801 (dizocilpine) or the competitive NMDAR antagonist 2-carboxypiperazin-4-yl-propyl-1-phosphonic acid (CPP) produced similar results. At lower drug doses, SS mice showed greater loco-motor activation than LS mice; and at higher doses, SS mice continued to be activated whereas LS mice became sedated. Brain levels of [³H]MK-801 were 40% higher in SS, compared with LS, mice. However, blood levels of [³H]MK-801 and [³H]CPP and brain levels of [³H]CPP were similar in the two lines. NMDARs were measured using quantitative autoradiographic analysis of in vitro [³H]MK-801 binding to SS and LS mouse brains. Significantly higher (20 to 30%) receptor densities were observed in the hippocampus and cerebral cortex of SS mice. Our results support the hypothesis that SS and LS mice differ in initial sensitivity to NMDAR antagonists and suggest that the line differences in the dose-response relationships for MK-801- and CPP-induced locomotor activity are qualitatively similar to those reported for ethanol. Differences in pharmacokinetics and number of NMDARs may contribute to, but are unlikely to entirely account for, the differential behavioral responsiveness of SS and LS mice to MK-801 and CPP.     

多巴胺D3受体对大鼠肾脏近曲小管上皮细胞多巴胺D4受体表达和功能的影响

目的:观察多巴胺D3受体(D3受体)对大鼠肾脏近曲小管(RPT)上皮细胞多巴胺D4受体(D4受体)表达和功能的影响.方法:以Wistar-Kyoto(WKY)大鼠RPT上皮细胞为研究对象,利用免疫印迹法观察D3受体激动剂PD128907刺激D3受体后D4受体表达的变化;采用哇巴因法测定Na+-K+-ATP酶(ATP为三磷酸腺苷)活性,观察D3受体激动剂PDl28907(10-7mol/L,24 h)预先作用后,D4受体激动剂PD168077(10-7 mol/L,15 min)对Na+-K+-ATP酶活性的影响.同时,探讨D3受体激动剂PDl28907影响D4受体表达的作用机制.结果:D3受体激动剂PDl28907刺激可明显增强RPT上皮细胞中的D4受体蛋白表达,该作用呈时间与浓度依赖性关系.D3受体激动剂PDl28907对D4受体蛋白表达的增强作用可被D3受体特异性抑制剂U99194A(10-6 mol/L)所阻断.磷脂酶C抑制剂U73122存在的情况下,D3受体激动剂PD128907刺激D3受体后对D4受体的促进表达效应受到显著抑制.与单用D4受体激动剂PD168077相比,在PDl28907(10-7 mol/L,24 h)预先刺激的情况下,D4受体激动剂PD168077对Na+-K+-ATP酶活性的抑制作用有所增强.结论:D3受体对大鼠RPT上皮细胞上D4受体表达和功能具有增强作用,此作用可能通过磷脂酶C信号途径发挥影响.     

Effect of Angiotensin II on Striatal Dopamine Release in the Spontaneous Hypertensive Rat

We have previously demonstrated that angiotensin II stimulates the release of dopamine from the normotensive rat striatum via the AT₁ receptor. In this study, the effect of angiotensin II-stimulated striatal dopamine release in the spontaneous hypertensive rat was compared to normotensive controls. In the spontaneous hypertensive rat, angiotensin II stimulated dopamine release to 169±13% (P<0.05) in the experimental period, with levels remaining high in the recovery phase, 158±16% (P<0.05). This effect was not significantly different from the response in normotensive controls, in which angiotensin II stimulated dopamine release to 149±18% (P<0.05) in the experimental period, with the effect also persisting through the recovery period, 244±62% (P<0.05). Thus, despite reports of increased activity of the brain angiotensin II and dopamine systems in the spontaneous hypertensive rat, there is no evidence of abnormal regulation of the striatonigral dopamine system.     

阿那白滞素对病毒性心肌炎小鼠的保护作用及对TLR4/TRAF6通路的影响

目的探究阿那白滞素对病毒性心肌炎小鼠的保护作用及对Toll样受体4(TLR4)与肿瘤坏死因子受体活化因子6(TRAF6)通路的影响。方法将雄性BALB/c小鼠平均分为正常组(A组)、模型组(B组)、阿那白滞素低剂量组(C组)与阿那白滞素高剂量组(D组)4组,每组10只。A组小鼠腹腔注射不含柯萨奇病毒B3(CVB3)稀释液;B组小鼠腹腔注射CVB3病毒悬浮液制备病毒性心肌炎模型;C组、D组均在B组基础上分别注射0.02mL/g、0.2mL/g的阿那白滞素。采用酶联免疫法测定心肌肌钙蛋白T(cTnT)、肌酸激酶同工酶(CK-MB)、超氧化物歧化酶(SOD)、丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白介素-1(IL-1)、白介素-6(IL-6)水平;制备心肌组织石蜡切片进行苏木素-伊红染色(HE染色)以及马松染色(Masson染色),细胞流式仪检测心肌细胞凋亡;逆转录-聚合酶链反应(RT-PCR)、蛋白质印迹(Westernblot)法测定心肌组织中TLR4、TRAF6、核因子-κB(NF-κB)、髓样分化蛋白88(MyD88)、TIR结构域接头分子(TRIF)mRNA表达。结果与A组比较,B组血清cTnT、CK-MB、MDA水平升高,SOD水平降低,差异有统计学意义(P<0.05);与B组比较,C组、D组cTnT、CK-MB、MDA水平降低,SOD水平升高,且D组较C组变化明显,差异均有统计学意义(P<0.05)。HE染色以及Masson染色显示,与A组比较,B组心肌组织病理评分、心肌纤维比例升高,与B组比较,C组、D组心肌组织病理评分、心肌纤维比例降低,且D组降低程度较C组明显,差异均有统计学意义(P<0.05)。C组、D组心肌组织凋亡率低于B组,D组心肌组织凋亡率低于C组,差异均有统计学意义(P<0.05)。与A组比较,B组TLR4、TRAF6、NF-κB、MyD88、TRIF的mRNA、蛋白表达均升高;与B组比较,C组TLR4、TRAF6、NF-κB、MyD88、TRIF的mRNA、蛋白表达降低,与C组比较,D组TLR4、TRAF6、NF-κB、MyD88、TRIF的mRNA、蛋白表达降低,差异均有统计学意义(P<0.05)。结论阿那白滞素对病毒性心肌炎小鼠心肌组织具有保护作用,可能与抑制TLR4/TRAF6信号通路相关。     

The Involvement of NMDA Receptors in Acute and Chronic Effects of Ethanol

Recent evidence indicates involvement of excitatory amino acid receptors sensitive to N-methyl-d-aspartate (NMDA) in the action of ethanol (EtOH). Pronounced inhibition of NMDA receptor function is seen in vitro with concentrations of EtOH corresponding to those present during alcohol intoxication in humans. The present study was devoted to investigate the role of NMDA receptors in the action of EtOH in rats. Acute experiments showed antagonism by EtOH of convulsions induced by intracerebroventricular injection of NMDA. A similar effect was seen with a high dose of diazepam. Convulsions induced by an agonist of another excitatory amino acid receptor subtype, kainate, were also inhibited by EtOH. An uncompetitive antagonist of NMDA receptors, 5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine maleate (MK-801), potentiated EtOH-induced loss of righting, but attenuated the hypothermic action of EtOH. Moreover, MK-801 inhibited audiogenic convulsions in EtOH withdrawn rats. At the same time the effect of a proconvulsive dose of NMDA was not enhanced. Tolerance to the myorelaxant action of both EtOH and MK-801 upon repetitive administration was seen. Also some degree of cross-tolerance was observed. Moreover, MK-801 failed to modify EtOH preference in rats. The present results support involvement of NMDA receptors in expression of some acute and subchronic actions of EtOH and in expression of EtOH withdrawal.     

The Effect of Sodium Depletion and Potassium Supplementation on Vasopressin,Renin and Catecholamines in Hypertensive Men

ABSTRACT Seventeen 50-year-old hypertensive men (157±4/110±2 mmHg, mean ± SE) were given low sodium diet for one week, which was supplemented with potassium the following week. The urinary Na⁺/K⁺ excretion ratio changed from 2:1 to 1:5 and 1:12, respectively, during dietary intervention. Arterial plasma vasopressin decreased by 3.4±1.7 ng/l (0.05>p<0.10) and urinary excretion of vasopressin was reduced by nearly 50% (p<0.001) during sodium depletion, while plasma noradrenaline increased by 38% (p<0.001) and plasma dopamine showed an increase by 58% (p<0.001). Plasma renin concentration increased four-fold during sodium depletion (p<0.001). With combined salt depletion and potassium supplementation, arterial plasma vasopressin decreased by 9.5±4.0 ng/l (p<0.05) compared to control. Urinary excretion of vasopressin together with plasma noradrenaline and dopamine were unchanged during the second week. The reduction of blood pressure was most marked during the first week (143±3/103±2 mmHg, p<0.05), but continued to fall also during the second week. Thus, during sodium restriction in middle-aged hypertensive men, blood pressure reduction occurs concomitantly with inhibited vasopressin release, despite enhanced renin and catecholamine release. Potassium supplementation during sodium restriction induces only minor changes in these variables.     

致死型约氏疟原虫感染DBA/2小鼠保护性免疫机制的研究

目的 观察约氏疟原虫(P.yoelii) 17XL感染DBA/2小鼠的免疫应答机制及免疫效应的动态变化。方法 1×10⁶ P.yoelii 17XL感染的红细胞经腹腔接种DBA/2小鼠, ELISA测定血清白细胞介素-12 (IL-12)、干扰素-γ( IFN-γ)、IL-4和IL-10的水平以及特异性抗体IgG水平。Griess反应检测脾细胞培养上清中一氧化氮(NO)含量。检测小鼠原虫血症、单核细胞百分率,观测其吞噬疟原虫现象。结果 感染小鼠第9天原虫血症高达46.9%,多数小鼠于感染后第20天左右自愈。感染后第6至16天,外周血查见有吞噬作用的单核细胞。感染后第1天起, IL-12水平开始升高; IFN-γ于第6天达最高水平, IL-4和IL-10分别于第9天和第15天达最高水平。脾细胞培养上清NO含量,分别于第6天和第20天显著升高。血清中特异性抗体IgG水平呈增高趋势,至第70天达最高水平。结论 Th1细胞的有效活化对遏制原虫血症和最终清除疟原虫具有重要意义。约氏疟原虫感染早期,单核-巨噬细胞对原虫血症的遏制起到关键作用。     

Effect of Intravenous Dopamine Infusion on Intramural Blood Flow Distribution and Fluid Absorption in the Feline Small Intestine

The aim of the study was to investigate the effects of dopamine on the intestinal mucosal blood flow and transport function. Dopamine was infused intravenously at 20 μg × kg^-1 × min^-1 in anesthetized cats. Total and intramural blood flow in an isolated jejunal segment was measured by a combined drop-flow and ⁸⁵Kr clearance technique. Net fluid transport was recorded by two independent perfusion methods. Unidirectional sodium transport was estimated from luminal ²²Na disappearance. Dopamine induced a pronounced mucosal vasodilatation up to 400% of control values. Concomitantly, net fluid and sodium absorption increased by 50%. The effect on sodium transport was due to a pronounced decrease in tissue-to-lumen sodium flux, a pattern similar to the one seen on (α-adrenergic stimulation. The effect of dopamine on blood flow was unaffected by phentolamine. 1 mg × kg^-1, whereas the absorptive response was abolished. The findings indicate that dopamine induces a mucosal vasodilatation via one mechanism (possibly dopaminergic) and enhances fluid transport via another mechanism, probably α-adrenergic.     

Risperidone and ritanserin but not haloperidol block effect of dizocilpine on the active allothetic place avoidance task

Spatial working memory or short-term place memory is impaired in schizophrenia. The efficiency of antipsychotic drugs, particularly of typical antipsychotics, on cognitive deficit in schizophrenia remains disputable. Inhibition of serotonin (5-HT) 2A/2C receptors is important for cognitive improvement in schizophrenic patients treated with antipsychotics. The aim of the present work was to establish the effect of the 5-HT2A/2C receptor antagonist ritanserin (2.5 or 5 mg/kg), the dopamine D2 antagonist haloperidol (0.1 or 1 mg/kg), and the atypical antipsychotic risperidone (0.1 mg/kg or 1 mg/kg), which is an antagonist of both 5-HT2A/2C and D2 receptors, on cognitive deficit induced by subchronic administration of dizocilpine (MK-801, 0.1 mg/kg). We used the active allothetic place avoidance (AAPA) task, requiring the rat to differentiate between relevant and irrelevant stimuli, in a way similar to disruption of information processing disturbed in schizophrenic patients. Our results show that treatment with 5-HT2A/2C receptor antagonists, regardless of their effect on D2 receptors, blocked the cognitive impairment produced by MK-801. Haloperidol did not sufficiently reduce the deficit in AAPA induced by MK-801. Interestingly, administration of risperidone and haloperidol alone, but not ritanserin, impaired the AAPA performance in intact rats. Ritanserin and risperidone actually improve cognition independently of their effect on locomotor activity in an animal model of schizophrenia-like behavior. This finding is in accordance with the assumption that some antipsychotics are primarily effective against cognitive dysfunction in schizophrenia.     

脑组织过表达犬尿氨酸酶的转基因小鼠对血压的影响

目的本研究旨在构建脑组织选择性过表达犬尿氨酸酶（Kynu）的转基因小鼠,在整体水平研究KYNU活性增强对血压的影响。方法构建在神经元特异性烯醇酶（NSE）启动子控制下的大鼠Kynu表达载体,采用受精卵原核注射的方法获得脑组织过表达Kynu的转基因小鼠。采用PCR鉴定转基因阳性小鼠;荧光实时定量逆转录PCR（Real Time RT-PCR）、蛋白免疫印迹技术（Western blot）免疫组织化学方法检测转基因的表达;高效液相色谱（HPLC）检测KYNU的活性;鼠尾法测量小鼠血压。结果转基因小鼠与同窝阴性对照小鼠相比,脑干组织中KYNU的表达有显著的差异（P〈0.01）,不同发育阶段转基因小鼠脑干组织Kynu活性与同窝阴性对照小鼠相比,存在显著差异（12周,0.1613±0.0153 vs.0.0019±0.0002 nmol/min/mg,P〈0.01;35周,0.5817±0.1476vs. 0.0038±0.0004 nmol/min/mg,P〈0.05;〉1年,0.1909±0.0115 vs.0.0036±0.0011 nmol/min/ mg,P〈0.01）。但两组小鼠的收缩压没有显著差异（12周,113.6±3.9 Vs.109.3±2.3 mmHg,P〉0.05;35周,114.6±2.5 vs.113.1±4.2 mmHg,P〉0.05;〉1年,121.3±2.6 vs.123.9±3.5 mmH8,P〉0.05）。给予游泳应激刺激后,两组小鼠间的血压也无显著差别。结论脑干组织Kynu的过表达并没有引起日间的和应激的血压值改变,KYNU在血压调节中的作用有待于进一步的研究。     

曲美他嗪对病毒性心肌炎小鼠的保护作用及其机制

目的:观察曲美他嗪对M株柯萨奇病毒B3(CVB3m)感染的病毒性心肌炎小鼠的保护作用并探讨其可能作用机制。方法:以CVB3m诱导的病毒性心肌炎Balb/c小鼠模型为研究对象。201只清洁级近交系4～6周龄雄性Balb/c小鼠随机分成5组。正常对照小鼠20只(正常组);病毒性心肌炎小鼠55只(心肌炎组);喂养曲美他嗪10 mg/(kg.d)的正常小鼠20只(药物对照组);喂养曲美他嗪10 mg/(kg.d)的病毒性心肌炎小鼠53只(低剂量治疗组);喂养曲美他嗪20 mg/(kg.d)的病毒性心肌炎小鼠53只(高剂量治疗组)。观察各组血清中肌钙蛋白I(cTnI)水平、血清中超氧化物歧化酶(SOD)、丙二醛(MDA)含量的变化以及心肌组织中Fas mRNA表达水平的变化。结果:小鼠感染CVB3m后第7天及第14天,与正常组及药物对照组比较,心肌炎组、低剂量治疗组和高剂量治疗组血清cTnI水平、MDA含量显著升高,SOD含量显著降低,Fas mRNA的表达显著增加,差异有统计学意义(P<0.05)。小鼠感染CVB3m后第7天,与心肌炎组比较,低剂量治疗组和高剂量治疗组血清cTnI水平显著降低,MDA含量显著降低,差异有统计学意义(P<0.05),与心肌炎组及低剂量组比较,高剂量治疗组SOD含量显著升高,Fas mRNA的表达显著减少,差异有统计学意义(P<0.05)。感染CVB3m后第14天,与心肌炎组比较,低剂量治疗组和高剂量治疗组血清cTnI水平、MDA含量显著降低,SOD含量显著升高,Fas mRNA的表达显著减少,差异有统计学意义(P<0.05),与低剂量治疗组比较,高剂量治疗组上述指标变化更明显,差异有统计学意义(P<0.05)。结论:曲美他嗪能够减少病毒性心肌炎中心肌细胞的损害。其机制可能与其抗氧化作用以及通过下调Fas mRNA水平抑制心肌细胞凋亡有关。     

多巴胺受体与其他血压调节系统的交互作用在高血压研究中的地位

肾脏是人体负责钠排泄的重要器官,多巴胺由于其强大的抑制肾脏钠重吸收作用而在原发性高血压的发生、发展中发挥重要作用。多巴胺受体的5个亚型均直接或间接通过与其他血压调节系统的交互作用,参与肾脏钠通道或血压的调节。现就多巴胺受体在调节机体血压和肾脏利钠、利尿作用中所发挥的重要作用作一综述。     

日本血吸虫感染对小鼠妊娠的影响

目的　了解日本血吸虫感染对小鼠妊娠状况的影响。　方法　 180只雌鼠 (♀ )分成 4组。实验组以日本血吸虫尾蚴 (15± 2 )条 /只经肤感染。 A组 (6 0只 ) ,感染 d40 与未感染的雄鼠 (♂ )合笼交配受孕 ;B组(70只 ) ,感染 d1 0 0 与♂合笼交配受孕 ;C组 (30只 ) ,感染后不与♂合笼。 D组 (2 0只 )为未感染对照组 ,与♂合笼交配受孕。分别观察各组妊娠期间病情变化及胚胎发育情况。在发情间期取感染组小鼠血清用放射免疫方法检测雌二醇 (E2 )和孕酮。　结果　与对照组比较 ,感染组小鼠雌二醇和孕酮均显著降低。感染组受孕率明显下降 ,而流产率、受孕鼠死亡率及流产死亡率均显著增高 ,随着合笼时间延长病死率显著增高。感染组新生鼠仔体重、身长与对照组比较其差别无显著性意义。　结论　感染血吸虫小鼠可致雌二醇及孕酮分泌抑制 ,影响受孕 ,并使妊娠鼠病情加重 ,增加妊娠并发症和病死率