Précipitation et prévention de l'abstinence chez le rat et la souris en état de dépendance aiguë. Comparaison de la naloxone,de la naltrexone et de la diprenorphine

Summary Abstinence signs were precipitated in rats by naloxone (1 mg·kg^-1 s.c.) injected at various times (from 1.5 to 16 h) after a single dose of morphine hydrochloride (15 or 50 mg·kg^-1 s.c.) administered incaqueous solution. Increasing the dose of morphine increased the latency of the phenomena and the duration of the underlying state shifts of signs as described by Bläsig et al. (1974) in chronically morphinized rats also occurred when increasing the dose of morphine and the time interval between the injections of morphine and of naloxone. Naltrexone and diprenorphine were also effective. These three antagonists, given before morphine, were able to prevent precipitated abstinence: however, naloxone was almost ineffective when the higher dose of morphine was used and when the time interval was long. In these latter conditions, naltrexone was definitely more effective and longer acting and diprenorphine still more so. The same characteristics were found for the protective action of the three antagonists in acutely morphinized mice and the same order for their potencies in precipitating abstinence in acutely morphinized mice. Like naloxone, naltrexone and diprenorphine facilitated a nociceptive reaction in normal mice.The abstinence signs precipitated in acutely morphinized rats or mice are probably not unmasked excitatory effects of morphine as such effects should have been increased rather than inhibited by previous administration of specific antagonists; they might correspond to potentiated effects of the antagonists themselves. The prevention by specific antagonists of the abstinence syndrome is most simply interpreted by antagonism (direct or indirect) of dependence induction, but other interpretations are not excluded.

     

小鼠自然老化过程中耳蜗的糖代谢障碍

应用定量组织化学技术分析了ＣＢＡ和Ｃ５７ＢＬ小鼠耳蜗中糖元代谢的改变，发现１８个月和３６个月龄ＣＢＡ小鼠的毛细胞和血管纹中，糖元含量比６周龄ＣＢＡ正常小鼠明显增高，说明在自然老化ＣＢＡ小鼠耳蜗中存在糖元储积现象。     

抗人喉癌单克隆抗体对荷瘤裸鼠放射免疫定位显像的观察

目的用喉癌裸鼠模型研究抗人喉癌单克隆抗体的免疫导向作用，为诊断和治疗提供依据和方向。方法用高效碘标法标记三株混合抗人喉癌单克隆抗体（ＭｃＡｂＬＣ）经腹腔注入人喉癌裸鼠模型体内，用单光子发射计算机断层（ｓｉｎｇｌｅｐｈｏｔｏｎｅｍｉｓｓｉｏｎｃｏｍｐｕｔｅｄｔｏｍｏｇｒａｐｈｙ，ＥＣＴ）扫描显像并测定肿瘤、血液和组织单位质量浓集的放射性占注入总放射性的百分比（％ＩＤ／ｇ）和肿瘤与主要器官组织的放射性比值（Ｔ／ＮＴ）。结果单克隆抗体在一定时限内能够选择性的浓集在移植瘤组织内，９６ｈ可获得满意的肿瘤显像，实验组肿瘤组织的％ＩＤ／ｇ为１８．８±０．６１，对照组肿瘤组织的％ＩＤ／ｇ为４．４６±０．８２，两组比较差异有显著性（Ｐ＜０．０１，ｔ＝３４．９７）。结论用放射性核素标记抗人喉癌单克隆抗体在活体内能选择性地与人喉癌细胞结合，用ＥＣＴ扫描可以识别肿瘤所在的部位和大小，对肿瘤病灶及转移病灶的定位诊断有一定的实用价值。     

A longitudinal,functional study of peripheral nerve recovery in the mouse

Objectives: To verify the validity of the recently described sciatic functional index for mice to monitor neuronal functional recovery over time using a blinded, randomized, and controlled evaluation. Study Design: Surgery was performed on the left sciatic nerves of 62 C57/BL mice after randomly assigning them to one of four surgical groups: sham surgery, sciatic nerve crush, nerve transection without repair, and nerve transection followed by epineurial suture repair. Sciatic functional indices were measured before surgery and then after surgery at 10-day intervals for 90 days, using a previously described formula. Results: Sham surgery did not affect nerve function when compared with preoperative values (P > .24). Crush surgery produced a reversible nerve injury that fully recovered after 20 days. Nerve transection without repair resulted in complete functional disability without recovery of function during the 90-day follow-up interval. When transected nerves were repaired, complete functional disability was noted at day 10, with subsequent functional recovery to 26% of function at day 30. This level of recovery persisted until the 60th postoperative day when muscle contractures resulted in progressive worsening of the index. There were statistically significant differences between the sciatic functional indices of each of the groups (P < .05). Conclusions: The previously described sciatic functional index for mice is an accurate indicator of the level of sciatic neuronal function during recovery. This index represents a method of evaluating neuronal function that may provide a better reflection of the recovery parameters that are important in clinical situations. The sciatic functional index will allow for study of sciatic nerve functional recovery in genetically engineered transgenic mice.     

金钱白花蛇药酒对小鼠镇痛作用的实验研究

目的:研究金钱白花蛇药酒的镇痛作用。方法:用小鼠热板致病法、小鼠酒石酸锑钾致扭体反应法,观察颈舒康颗粒的镇痛作用。结果:颈舒康颗粒能对抗用热板法、酒石酸锑钾所致的疼痛。结论:颈舒康颗粒有较好的镇痛作用。     

一种小鼠肠道纤维化模型建造的方法及评价

目的 探究一种使用酒精建造C57BL/6小鼠肠道纤维化模型的方法。方法 将6周龄C57BL/6小鼠根据不同酒精浓度分为正常对照组、50%乙醇组、三硝基苯磺酸(TNBS)/30%乙醇组、TNBS/50%乙醇组,采用灌肠液灌肠方式造模,每周灌肠1次,持续5周,第6周处死后取结直肠。整个实验期间观察小鼠生存状态、体重变化及生存率,每天进行小鼠疾病活跃指数(DAI)评价。固定包埋后,采用苏木精-伊红染色检测肠道黏膜以及腺体结构完整性;马森三色染色法检测小鼠肠道胶原沉积情况;免疫组织化学染色检测纤维化蛋白α-平滑肌肌动蛋白(α-SMA)的表达量。结果 与正常对照组比较,50%乙醇组、TNBS/30%乙醇组、TNBS/50%乙醇组的黏膜破损、腺体丢失比例、纤维化蛋白α-SMA表达明显高于正常对照组,并且50%乙醇组、TNBS/30%乙醇组、TNBS/50%乙醇组的DAI评分更高、胶原沉积更多,且TNBS/50%乙醇组高于TNBS/30%乙醇组,50%乙醇组与TNBS/30%乙醇组相近。结论 与正常组比较,50%乙醇组小鼠各时间点DAI评分均明显增高,整体纤维化程度与TNBS/30%乙醇组类似,单纯使用乙醇可以建造小鼠肠道的纤维化模型。     

人突变Lumican基因转基因小鼠屈光变化特点

目的：探讨人突变Lumican基因转基因小鼠生后不同时间屈光状态及其变化特征。方法实验研究。54只（雄性27只,雌性27只）人突变Lumican基因（cDNA 596T>C）转基因小鼠,于生后3、4、5、6、8、10、12、16、20周共9个时间点分别通过随机数字表法随机选取6只（雄性3只,雌性3只）转基因小鼠,快速散大瞳孔后检影验光测量屈光度数。对比相同时间点转基因小鼠双眼间及雌雄性别间的屈光度数,采用配对t检验;不同时间点转基因小鼠屈光度数的比较采用非参数多个独立样本Kruskal?Wallis H检验,两两组间屈光度数比较采用非参数两个独立样本Mann?Whitney U检验。结果同周龄组转基因小鼠双眼间比较屈光度数差异无统计学意义：第20周转基因小鼠右左眼屈光度均值分别是（1.50±0.45）和（1.25±0.42）D,（t=-0.889,P>0.05）,第3周转基因小鼠右左眼屈光度均值分别是（-2.50±2.59）和（-2.50±4.32）D,（t=0.000,P>0.05）;同周龄组不同性别转基因小鼠眼间比较屈光度数差异无统计学意义：第3周转基因小鼠雌雄性别眼屈光度均值分别是（-0.5±3.83）和（-4.17±1.94）D,（t=2.079,P>0.05）,第12周转基因小鼠雌雄性别眼屈光度均值分别是（1.50±0.84）和（1.50±1.87）D（t=0.000,P>0.05）;不同周龄组转基因小鼠屈光度数差异有统计学意义（H=20.910,P<0.05）;两两组间比较显示转基因小鼠第3周与第6周屈光度数差异有统计学意义（Z=-3.259,P<0.001）,其余各周之间比较屈光度数差异均无统计学意义（P>0.001）。结论人突变Lumican基因转基因小鼠出生后3周时为近视,随时间增加向远视发展,第6周远视屈光度数达到最大,8～20周时远视屈光度数逐渐减小并趋于稳定。（中华眼科杂志,2015,51：527-531）     

解脲脲原体血清型3在小鼠生殖道中的致病性

目的 探讨不同浓度解脲脲原体血清型3(UU3)在小鼠生殖道中的致病性.方法 将156只昆明小鼠按完全随机设计法分为A、B、c组(每组各48只)及对照组(12只)共4组.将3种不同浓度的UU3接种至各实验组小鼠阴道内,各组的浓度分别为:A组1×107 copy/g,B组1×106copy/g,c组1×105 copy/g;对照组仅接种UU液体培养基.于接种后第1、3、7、14、21、35天每次随机处死A、B、c组各8只及对照组2只小鼠,取宫颈管分泌物,荧光定量PCR(FQ-PCR)技术检测各组UU3的浓度及阳性率;取宫颈、子宫内膜及输卵管组织,光镜下观察其形态,并计算致病率.结果(1)A、B、C 3组UU3总阳性率分别为63%(30/48)、50%(24/48)和17%(8/48),3组间比较,差异有统计学意义(P<0.01).接种后1、3、7、14、21、35 d小鼠的UU3阳性率,A组分别为8/8、7/8、6/8、5/8,4/8和0,B组分别为7/8、5/8、5/8、4/8、3/8和0,C组分别为3/8、2/8、2/8、1/8、0和0;对照组各时间点均为0.接种后1 d的UU3阳性率3组间比较,差异有统计学意义(P<0.05);其他各时间点3组间比较,差异均无统计学意义(P>0.05).(2)在UU3检测阳性者中,A、B、C组的UU3浓度在接种后1、3、7、14、21 d分别为1.70×107、3.75×106和1.45×105copy/g,8.26×10+6、2.56×106和1.07×105copy/g,4.04×106、1.37×106和5.43×104copy/g,2.86×106、6.72×105和4.68×103copy/g,2.41×105、1.12×105和0 copy/g.除接种后21 d外,接种后各时间点A、B、C 3组的UU3浓度比较,差异均有统计学意义(P<0.05);A、B组内接种不同时间点的UU3浓度比较,差异均有统计学意义(P<0.05);C组接种不同时间点的UU3浓度比较,差异无统计学意义(P>0.05).(3)接种后7～35 d,A、B、C 3组的总致病率分别为56%(18/32)、44%(14/32)和6%(2/32),3组间比较,差异有统计学意义(P<0.01);接种后7、14、21、35 d小鼠的致病率,A组分别为5/8、5/8、4/8和4/8,B组分别为4/8、4/8、3/8和3/8,C组分别为1/8、0、1/8和0;对照组各时间点均为0.除接种后14 d外,各时间点A、B、C 3组间致病率比较,差异均无统计学意义(P>0.05).结论在小鼠生殖道局部接种不同浓度的UU3,其致病性不同.当UU3浓度≥1×106copy/g时,其致病性明显增强.     

尼莫地平对神经元退行性变模型小鼠脑组织中铁离子的影响研究

目的:探讨尼莫地平对神经元退行性变模型小鼠脑组织中铁离子的影响。方法:取小鼠随机分为假手术组(生理盐水)、模型组(生理盐水)和尼莫地平高、中、低(80、40、20mg.kg-1)剂量组,每组35只,后4组脑室内注射0.25氯化铝2μL,每天1次,连续5d,建立神经元退行性变小鼠模型,假手术组注射等体积人工脑脊液;5d后各组灌胃给予相应药物,每天2次,连续30d,末次灌胃24h后观察其脑组织的病理学变化,考察海马组织中丙二醛(MDA)、血红素加氧酶-1(HO-1)蛋白、铝离子和铁离子水平变化。结果:与模型组比较,尼莫地平高剂量组神经元损伤明显减轻,其中MDA、HO-1蛋白和铁离子水平明显降低(P<0.05);其余指标及尼莫地平中、低剂量组各项指标均无明显变化。结论:尼莫地平可能通过抑制HO-1蛋白表达维持铁离子代谢平衡,发挥缓解神经元退行性变的作用。     

去甲斑蝥素对G422脑胶质瘤抑制作用的体内研究

目的:研究去甲斑蝥素(NCTD)体内对脑胶质瘤G422细胞的抑制作用。方法:建立G422细胞小鼠移植瘤模型,将荷瘤小鼠随机分为模型组、CTX阳性对照组及NCTD高、中、低剂量组(100、50、25 mg.kg-1),每组10只,另设10只为正常对照组,正常对照组每日给生理盐水灌胃,CTX和NCTD组采用腹腔注射方式给药,10 d后双抗体夹心ABC-ELISA法测sIL-2R的含量;酶联免疫ELISA法测IFN-γ含量;剥瘤,计算抑瘤率;剥瘤的同时取脾脏,计算脾脏指数;MTT法检测NCTD对荷瘤小鼠脾脏T、B淋巴细胞增殖的影响。结果:NCTD可降低荷瘤小鼠血清sIL-2R含量,提高IFN-γ含量,抑制G422细胞小鼠移植瘤的生长;对脾脏指数影响较少,可促进荷瘤小鼠的T、B淋巴细胞增殖。结论:NCTD体内外可抑制G422细胞生长,并具有免疫调节作用。