重度联合免疫缺陷小鼠的繁育及其应用初报

应用带过滤罩的透明鼠在层流柜内繁育Ｔ和Ｂ淋巴细胞缺失的重度联合免疫缺陷（ｓｃｉｄ）小鼠获得成功，１９９３年５月至１９９４年４月，共繁育ｓｃｉｄ小鼠２２１只，寿命均超过１２个月。平均每窝产仔数为５．５只，显著低于对照组ＢＡＬＢ／ｃ小鼠，不育率为１４．９％，离乳率为８８．２％，与ＢＡＬＢ／ｃ小鼠相比均无明显差异。ｓｃｉｄ小鼠４～１０周龄的体重与同龄ＢＡＬＢ／ｃ小鼠相比无明显差异，微生物学检测均符合ＳＰ     

赤灵芝的致突变性试验

使用赤灵芝的水提取液、乙醇（３０％）提取液进行鼠伤寒沙门氏菌回复、小鼠骨髓多染红细胞微核和雄小鼠精子畸变等三种致突变试验。剂量为１０００μｇ．皿＾－１和５０００μｇ／皿＾－１的鼠伤寒沙门氏菌回复试验的结果为阴性。小鼠在服用７５００ｍｇ．ｋｇ＾－１的水提取液或２５００ｍｇ．ｋｇ＾－１的醇提取液时，微核试验和精子畸变试验结果均为阴性。     

The effects of norepinephrine transporter inactivation on locomotor activity in mice.

BACKGROUND: Acute administration of different classes of antidepressants can enhance or reduce spontaneous locomotor activity in a novel environment, but the effects of chronic antidepressant treatment on spontaneous locomotor activity in novel and familiar environments are less well characterized. Because norepinephrine is an important regulator of spontaneous locomotor activity, we speculated that norepinephrine transporter blockade contributes to the effects of some antidepressants on spontaneous locomotor activity. METHODS: Antidepressant drugs (reboxetine, desipramine, imipramine, venlafaxine, bupropion) were administered acutely (intraperitoneal) or chronically (via osmotic minipump) to control and norepinephrine transporter knockout mice, and spontaneous locomotor activity in novel or familiar environments was recorded. RESULTS: Acute treatment with most norepinephrine transporter-blocking antidepressants decreased spontaneous locomotor activity in a novel environment, whereas chronic treatment decreased spontaneous locomotor activity in both novel and familiar environments. The exception was bupropion, a dual norepinephrine transporter/dopamine transporter blocker, which tended to increase spontaneous locomotor activity. Coadministration of reboxetine and the dopamine transporter blocker GBR 12909 also increased spontaneous locomotor activity. Norepinephrine transporter knockout mice had low basal spontaneous locomotor activity, which was increased by bupropion, whereas reboxetine had no effect in norepinephrine transporter knockout mice. CONCLUSIONS: Acute or chronic inactivation of the norepinephrine transporter decreases spontaneous locomotor activity in novel and familiar environments unless coupled with dopamine transporter blockade.     

肉苁蓉多糖对衰老小鼠脂质过氧化的影响

目的:研究肉苁蓉多糖(polysacchridesofcistanchedeserticolaY.C.Ma,PCD)对亚急性衰老小鼠的抗 脂质过氧化作用。方法:使用D 半乳糖造成小鼠亚急性衰老模型,观察PCD对亚急性衰老小鼠血液和肝脏组 织中超氧化物岐酶(SOD)、脂质过氧化物(LPO)的含量的影响。结果:灌服肉苁蓉多糖衰老小鼠的血液和肝脏 组织中SOD明显高于模型组(P<0.05);LPO的含量明显低于模型组(P<0.05)。结论:肉苁蓉多糖具有明显 的抗脂质过氧化功能,防止亚急性衰老小鼠的组织脂质过氧化损伤。     

异丙酚对MPTP损伤的小鼠黑质多巴胺神经元的保护作用

目的　观察异丙酚对 1 甲基 4 苯基 1,2 ,3 ,6 四氢吡啶 (1 methyl 4 phenyl 1,2 ,3 ,6 tetrahydropyridineMPTP)损伤的小鼠纹状体多巴胺神经元的影响以及可能的作用机制。方法　给予Propofol 10 0mg/ (kg·d)后注射MPTP 2 0mg/ (kg·d) ,用药 6d。 12d后分离纹状体应用高效液相 -电化学方法检测纹状体多巴胺、二羟基苯乙酸及高香草酸的含量水平 ,应用12 5I- β-CIT放射性配基和免疫组化的方法检测多巴胺转运蛋白的活性和黑质神经元的损伤情况。结果　异丙酚可增加MPTP模型鼠多巴胺及其代谢产物的含量 ,异丙酚处理组DA ,DOPAC ,HVA的含量分别为 (8.2 417± 1.692 ) μg/ g、(1.3 81± 0 .486) μg/g和 (1.63 3 9± 0 .5 73 ) μg/ g ,与MPTP损伤组比较 ,明显增加。异丙酚亦可抑制黑质酪氨酸羟化酶 (TH)阳性神经元的减少。MPTP组注射MPTP 6d后 ,纹状体DAT为 (5 .3 13± 0 .64 2 )与正常组 (6.992± 0 .5 48) μg/ g比较显著下降 (P <0 .0 1) ,P +M组纹状体DAT为 (6.5 65± 0 .40 5 ) ,明显高于MPTP组 (P <0 .0 1) ,即减轻纹状体内多巴胺转运蛋白密度下降。结论　异丙酚对MPTP损伤的DA神经元具有一定的保护作用 ,其保护作用可能与抑制多巴胺转运蛋白活性有关     

A review of Disrupted-In-Schizophrenia-1 (DISC1): neurodevelopment, cognition, and mental conditions.

Disrupted-In-Schizophrenia-1 (DISC1) is a promising candidate gene for schizophrenia (SZ) and bipolar disorder (BP), but its basic biology remains to be elucidated. Accumulating genetic evidence supports that DISC1 is associated with some aspects of cognitive functions relevant to SZ and BP. Here, we provide a summary of the current updates in biological studies of DISC1. Disrupted-In-Schizophrenia-1, preferentially expressed in the forebrain, has multiple isoforms with potential posttranslational modifications. Disrupted-In-Schizophrenia-1 protein occurs in multiple subcellular compartments, which include the centrosome, microtubule fractions, postsynaptic densities, actin cytoskeletal fractions, the mitochondria, and the nucleus. Recent studies have clarified that DISC1 mediates at least centrosome-dynein cascade and cyclic adenosine monophosphate (cAMP) signaling. Furthermore, both cytogenetic and cell biological studies consistently suggest that an overall loss of DISC1 function (either haploinsufficiency or dominant-negative, or both) may be associated with SZ and BP. On the basis of these findings, production of DISC1 genetically engineered mice is proposed as a promising animal model for SZ and BP. Several groups are currently generating DISC1 mice and starting to characterize them. In this review, the advantages and disadvantages of each animal model are discussed.     

Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma

BACKGROUND: Microbial intestinal colonization in early in life is regarded to play a major role for the maturation of the immune system. Application of non-pathogenic probiotic bacteria during early infancy might protect from allergic disorders but underlying mechanisms have not been analysed so far. OBJECTIVE: The aim of the current study was to investigate the immune effects of oral application of probiotic bacteria on allergen-induced sensitization and development of airway inflammation and airway hyper-reactivity, cardinal features of bronchial asthma. METHODS: Newborn Balb/c mice received orally 10(9) CFU every second day either Lactobacillus rhamnosus GG or Bifidobacterium lactis (Bb-12) starting from birth for consecutive 8 weeks, during systemic sensitization (six intraperitoneal injections, days 29-40) and airway challenge (days 54-56) with ovalbumin. RESULTS: The administration of either Bb-12 or LGG suppressed all aspects of the asthmatic phenotype: airway reactivity, antigen-specific immunoglobulin E production and pulmonary eosinophilia (mean: 137 vs. 17 and 13 cellsx10(3)/mL, respectively). Antigen-specific recall proliferation by spleen cells and T-helper type 2 cytokine production (IL-4, IL-5 and IL-10) by mesenteric lymph node cells also showed significant reduction, while TGF production remained unchanged. Oral LGG administration particularly suppressed allergen-induced proliferative responses and was associated with an increase in numbers of TGF-beta-secreting CD4+/CD3+ T cells in mesenteric lymph nodes (6.5, 16.7%) as well as nearly 2-fold up-regulation of Foxp3-expressing cells in peribronchial lymph nodes. CONCLUSIONS: Neonatal application of probiotic bacteria inhibits subsequent allergic sensitization and airway disease in a murine model of asthma by induction of T regulatory cells associated with increased TGF-beta production.     

刺五加对~(60)Co-γ射线照射后小鼠胸腺效应的实验研究

采用180只成年小白鼠(雌雄各半),其中168只经一次总剂量为4Gy的~(60)Co—γ射线照射,造成造血放射损伤,再从其中随机选出56只膜腔注射刺五加注射液作为实验用药组,其余小白鼠随机分为盐水对照组(56只),空白对照组(56只)及正常对照组(12只)。实验结果显示。实验用药组的胸腺细胞超微结构的恢复比同期对照组快,胸腺组织DNA含量比同期对照组高。因此,我们认为刺五加可促进辐射损伤后小白鼠胸腺细胞结构的恢复。     

乙型肝炎病毒转基因小鼠体内肝靶向反义RNA抗病毒疗效研究

目的：探讨半乳糖修饰的反义RNA真核表达质粒在乙型肝炎病毒转基因小鼠体内的抗病毒作用。方法：以半乳糖多聚赖氨酸（Gal-PLL)作肝靶向载体，将乙型肝炎病毒基因C区的反义RNA真核表达重组质粒（pCEP4-aC）制备为Gal-PLL－pCEP4-aC。将24只血清HBV DNA、HBsAg阳性的小鼠，随机等分为Gal-PLL－pCEP4-aC治疗组、Gal-PLL-pCEP4对照组和生理盐水阴性对照组，于实验第1天尾静脉分别注射Gal-PLL－pCEP4-aC、Gal-PLL－pCEP4（100μg/只）和等体积的生理盐水，观察治疗前后血清HBV DNA以及HBsAg变化。结果：Gal-PLL－pCEP4-aC治疗组21天时血清HBV－DNA转阴率62．5％（5／8），且7，14，21天时血清HBsAg明显降低；而Gal-PLL－pCEP4组血清HBV DNA转阴1只（1／8），生理盐水组8只均未转阴，两组用药后血清中HBsAg与用药前比较差异性均不明显（P＞0．05）。结论：肝靶向反义RNA能在乙肝基因小鼠体内抑制HBV的复制和抗原表达。