饮酒促进TA2小鼠乳腺癌的发生及机制探讨

目的探讨酒精是否促进小鼠乳腺癌的发生及可能的作用机制。方法建立饮酒TA2小鼠模型,用ANALOX AM1酒精分析仪检测TA2小鼠血液的酒精浓度,确保动物模型的建立;观察比较酒精组TA2小鼠(饮用含2%酒精的无菌水)与对照组TA2小鼠(饮用不含酒精的无菌水)的乳腺癌发生率、肿瘤的生长速度以及肿瘤的大小;酶联免疫法(ELASA)检测两组小鼠血清中雌激素水平的差异。结果饮酒组TA2小鼠自发乳腺癌的比例显著增加(P0.05),成瘤平均天数明显缩短(P0.05),生成肿瘤的重量和体积均有增加但差异无显著性(P0.05)。饮酒组TA2小鼠体内的雌激素水平明显升高(P0.05)。结论酒精促进TA2小鼠乳腺癌的发生,该作用可能通过雌激素水平的增加来实现。     

怀孕前后酒精摄入对雌鼠植入前胚胎DNA甲基化模式建立的影响

女性怀孕前后饮酒会对胎儿的发育及神经系统造成不利影响,称为“胎儿酒精综合征”（fetal alcohol spectrum disorders,FASD）。小鼠通常作为研究该病的动物模型。该实验采用体外培养技术及体内冲胚法研究雌鼠怀孕前后酒精摄入对各期植入前胚胎全基因组DNAT基化模式建立的影响。小鼠植入前胚胎体外培养实验发现,体外实验组I（怀孕前酒精处理组1,除8-cell外,其他各期胚胎的DNA甲基化水平明显低于体外对照组;体外实验组II（正常胚胎在含乙醇的培养基中培养）,各期植入前胚胎DNA甲基化水平均明显低于体外对照组。体内实验发现,体内实验组I（怀孕前酒精处理组）与体内的实验组II（怀孕后酒精处理组）,各期植入前胚胎DNA甲基化水平明显低于体内对照组。体内、外实验结果表明：受精前后酒精对各期植入前胚胎DNA甲基化模式的正确建立造成紊乱,该结果可为进一步揭示FSAD发病机制提供一定的实验基础。     

雷洛昔酚对大鼠垂体的作用

目的 观察雷洛昔酚是否能诱发出催乳素瘤的动物模型以及对PRL水平的影响,以研究雷洛昔酚对大鼠垂体的作用.方法 雌性Wistar大鼠切除卵巢后,分别在皮下埋植含有雷洛昔酚、雌激素和空白硅胶管,术后8周处死大鼠,检测大鼠体重变化、垂体重量变化、血清催乳素(PRL)水平和垂体组织学变化.结果 雷洛昔酚组与阴性对照组大鼠体重无明显统计学差异,与雌激素组大鼠体重具有统计学差异(P＜0.05);雷洛昔酚组与阴性对照组大鼠垂体重相比无明显差异,与雌激素组大鼠垂体重相比具有统计学差异(P＜0.05);雌激素组大鼠血清PRL水平最高,阴性对照组血清PRL水平最低,雷洛昔酚组介于两者之间,分别与雌激素组、对照组相比较差异均具有统计学意义(P＜0.05);雷洛昔酚组与对照组垂体病理为正常细胞形态,雌激素组垂体病理为PRL瘤表现.结论 雷洛昔酚对大鼠垂体有一定的影响,但不能诱发催乳素瘤.     

雌激素替代治疗去卵巢大鼠血清一氧化氮含量的变化

目的建立雌激素替代治疗动物模型,观察其血清中一氧化氮(NO)含量的变化.方法取40只雌性大鼠切除双侧卵巢,随机分成四组A组假手术组;B组单纯去卵巢组;C组去卵巢+雌激素治疗组(隔日肌注苯甲酸雌二醇5μg);D组去卵巢+雌孕激素治疗组(隔日肌注苯甲酸雌二醇5μg,黄体酮1mg),两月后检测血清中雌二醇(E2)、孕酮(P)及NO2-/NO3-的含量.结果(1)卵巢切除后血清E2、P和NO2-/NO3-浓度显著降低;(2)雌激素治疗组和雌孕激素治疗组血清E2和NO2-/NO3-的含量及雌孕激素治疗组血清P的含量,略低于A组而显著高于去卵巢组.结论所建立的动物模型可以模拟绝经及绝经后的小剂量雌激素替代治疗,动物模型体内雌激素浓度与具有抗衰老作用的NO浓度呈相互平行的变化关系,雌激素可能通过NO达到延缓衰老作用.     

苦瓜皂甙对衰老动物内分泌功能的影响

目的 :探讨苦瓜皂甙对衰老动物内分泌功能的调节作用。方法 :15月龄雌性老年昆明小鼠 ,随机分为老年对照组、实验 1组和实验 2组三组 ,同时准备 4月龄雌性昆明小鼠作青年对照组 ,其中两对照组饮水为普通水 ,两个实验组饮水分别含有 10 0mg/L及 2 0 0mg/L苦瓜皂甙 ,饲养 5周后取血清标本待测。同时 ,取 12月龄大鼠胸腺细胞培养 ,检测不同浓度苦瓜皂甙对雌激素受体蛋白表达的影响。结果 :与青年对照组相比 ,衰老小鼠血清ACTH、雌二醇水平显著降低。与老年对照组相比 ,两实验组血清雌二醇水平均明显升高 ,ACTH水平有升高趋势 ,但只有高剂量组有显著性 ;两组之间所有指标均没有显著性差异。体外实验发现 ,苦瓜皂甙明显促进雌激素受体蛋白的表达 ,却不影响其mRNA水平。结论 :苦瓜皂甙可通过调节ACTH分泌及雌激素受体表达来改善衰老机体内分泌功能     

酒精摄入量对小鼠肠道微生物、酶活性和血常规的影响

【背景】酒是影响机体健康的一把"双刃剑",饮酒对机体肠道微生态体系具有重要影响。【目的】研究不同酒精摄入量对小鼠肠道微生物、酶活性及血常规的影响,从肠道微生态和血常规角度探讨饮酒对身体健康的影响及作用机制。【方法】将SPF(Specific pathogen free)级实验小鼠随机分为对照组、低酒精量摄入组、中酒精量摄入组和高酒精量摄入组。对照组给予蒸馏水饮用,其余各组分别给予10%、20%和30%(体积比)的酒精水溶液作为小鼠的唯一饮用水,连续1个月后采集回肠内容物进行微生物和酶活性分析,采集眼球血进行血常规分析。【结果】与对照组相比,低酒精量摄入组小鼠肠道内乳酸菌数量显著增加(P0.05),大肠杆菌和细菌总数显著降低(P0.01或P0.05);高酒精量摄入组小鼠肠道乳酸菌、双歧杆菌数量显著降低(P0.01);与低酒精量摄入组和中酒精量摄入组相比,高酒精量摄入组小鼠肠道木聚糖酶、纤维素酶、蛋白酶和淀粉酶活性显著升高(P0.01);与对照组相比,低酒精量摄入组小鼠的红细胞比容显著降低(P0.05)。【结论】高酒精摄入量小鼠肠道有益菌群数量相对减少,肠道屏障功能受到影响;低酒精摄入量能调节小鼠肠道菌群结构和消化酶相对活性。     

耐甲氧西林金黄色葡萄球菌诱导SKH-1无毛小鼠菌血症模型

目的建立SKH-1无毛小鼠感染MRSA致菌血症模型的方法及其评价体系。方法 62只SPF级SKH-1无毛小鼠随机分成PBS对照组、低剂量模型组、高剂量模型组及给药组,尾静脉注射无菌PBS至对照组小鼠体内,其余各组小鼠尾静脉注射相应剂量MRSA(ST-239)菌悬液,从体重、死亡率、血常规、血液细菌浓度、主要器官荷菌量及病理改变等方面对模型进行评价,并用抗生素替考拉宁对模型进行检验。结果各组感染小鼠体重均下降明显,血常规指标改变明显;高剂量组死亡率高,血液中细菌浓度较高,肝、肾等多组织器官播散严重,皮肤可见多发性脓肿灶;使用替考拉宁能显著降低小鼠死亡率,减轻主要器官的损伤程度。结论应用MRSA菌株可成功诱导建立SKH-1无毛小鼠菌血症模型,模型具有病理特征明显及观察简便的优点,为相关药物评价研究提供了一个理想的动物模型。     

酒精性心肌病大鼠心肌解偶联蛋白2表达及能量代谢变化

目的:观察心肌解偶联蛋白2(uncoupling protein 2,UCP2)在酒精性心肌病(alcoholic cardiomyopathy,ACM)时表达变化及对心肌能量代谢的影响.方法:将Wistar大鼠分为三组,酒精组(A组,10只)、少量饮酒组(B组,7只)和对照组(C组,7只),三组给予相同饮食,酒精组通过采取逐渐增加饮用酒精浓度并长期定量摄入的方法建立ACM模型,少量饮酒组长期饮用少量低浓度酒精,对照组以水代酒.6个月后心脏彩超测定心功能;计算左室/体重指数;RT-PCR法测定心肌组织UCP2 mRNA表达;Western blot法测定心肌UCP2蛋白表达;高效液相色谱分析法测定心肌三磷酸腺苷酸(ATP)、二磷酸腺苷酸(ADP)、单磷酸腺苷酸(AMP)和磷酸肌酸(PCr)含量.结果:酒精组左心室射血分数和左心室短轴缩短率均低于对照组和少量饮酒组(P均＜0.01),左心室舒张末期内径则高于对照组和少量饮酒组(P＜0.01),左室/体重指数明显增加(P＜0.01);酒精组UCP2 mRNA及蛋白表达高于对照组和少量饮酒组(P均＜0.01);酒精组ATP、ADP、AMP和PCr较对照组和少量饮酒组明显减少(P均＜0.01),相关性分析显示心肌组织ATP水平与UCP2蛋白表达呈显著负相关(r=0.896,P＜0.01).结论:ACM时心肌UCP2表达明显增加,导致心肌能量代谢障碍,恶化心脏功能.     

诱发性2型糖尿病小鼠模型与自发性db/db小鼠特性的比较

目的建立诱发性2型糖尿病小鼠模型,并将其与自发性2型糖尿病小鼠db/db进行比较分析。客观评价两种2型糖尿病小鼠模型,为糖尿病研究中动物模型的选择与实际应用提供实验依据。方法高脂饲料喂养C57BL/6J小鼠4周,腹腔连续3次注射STZ,建立诱发性2型糖尿病小鼠模型。感染后4周,大体肉眼观察小鼠的肝脏、肾脏,测定糖耐量,血清生化指标及血清细胞因子IL-2、IL-4、IL-6、IFN-γ、TNF-α、IL-17、IL-10表达量,将其与同龄的自发性2型糖尿病小鼠db/db进行比较分析。结果肉眼观察发现,两组模型小鼠的肝脏、肾脏与对照组均具有明显差异。糖耐量分析中,两组模型小鼠与对照组小鼠各时间点的血糖值均具有统计学差异（P〈0.05）,耐糖功能低下,两组模型小鼠间血糖值无统计学差异。血液生化指标中,与对照组小鼠相比,两组模型小鼠GLU、CHOL、LDLC明显升高（P〈0.05）;两组模型小鼠相互比较,诱发性2型糖尿病小鼠血脂水平较高（P〈0.05）。免疫指标比较显示：除IL-2外,两组模型小鼠血清中细胞因子水平均较对照组小鼠明显升高（P〈0.05）,而db/db小鼠血清中细胞因子表达较诱发性糖尿病小鼠高,其中IL-6、IFN-γ、TNF-α具有显著性差异（P〈0.05）。结论两组2型糖尿病模型小鼠均在一定程度上模拟了人类糖尿病患者症状,但由于糖尿病产生的原因不同而存在着一定的差异,研究者可根据实际需要参照相关数据进行选择。     

肝硬化门脉高压症大鼠模型制作方法的探讨

目的：建立稳定可靠的肝硬化门脉高压大鼠动物模型。材料与方法：50只雄性sD大鼠,随机分为3组。正常对照组10只,行假手术,给予正常饮食。肝硬化A组20只,先行左肾上腺静脉结扎,然后给予初始浓度为0．03％的硫代乙酰胺（thioacetamide,TAA）溶液作为饮用水并根据大鼠体重变化调节给药浓度。肝硬化B组20只,行假手术,给予固定浓度为0．03％TAA溶液。给药时间为14周。结果：肝硬化A组大鼠死亡率为0,肝硬化形成率达到100％。肝硬化B组大鼠死亡率15％,肝硬化形成率75％。肝硬化A组大鼠的门静脉压力明显高于肝硬化B组和对照组。结论：采用左肾上腺静脉结扎并根据体重变化调节TAA给药浓度可建立稳定可靠的肝硬化门脉高压大鼠动物模型。     

四种小鼠便秘模型建立方法的比较

目的i初步探讨四种小鼠便秘模型建模方法的效果。方法：40只小鼠随机分为正常对照组（8只）和实验组（32只）,实验组分别采用经口灌胃止泻剂复方地芬诺酯、禁水不禁食、经口灌胃胃粘膜保护剂硫糖铝及经口灌胃冰水四种方法建立小鼠便秘模型,处理后观察四种不同方法建立的小鼠便秘模型首粒黑便排便时间、2小时内排便粒数及排便重量的差异。结果：与正常对照组比较,灌胃复方地芬诺酯、禁水不禁食、硫糖铝及冰水法四种造模方法均可使小鼠首粒黑便排便时间显著延长、2小时内排便粒数及排便重量显著减少（P〈0．05）。但采用复方地芬诺酯、禁水不禁食法处理的小鼠较经口灌胃硫糖铝及经口灌胃冰水诱导的小鼠首粒黑便排便时间显著延长、2小时内排便粒数及排便重量亦显著减少（P〈0．01）。结论：采用复方地芬诺酯、禁水不禁食方法建立小鼠便秘模型更加简单、有效。     

中药Ⅰ号方对APP/PS1双转基因AD小鼠模型行为和精神症状的影响

目的 研究中药Ⅰ号方( PN-1)对APP/PS1双转基因AD小鼠模型行为和精神症状的影响.方法将5月龄的APP/PS1双转基因AD小鼠随机分为模型组(vehicle)、安理申(Aricept)治疗组(2 mg/kg)、PN-1低(0.6g/kg)、中(1.2 g/kg)、高(2.4 g/kg)剂量组,并以同窝阴性的C57B L/6小鼠作为正常对照组(WT),每组16只,雌雄各半.绘药组小鼠每天灌胃给药1次,同时模型组及正常组小鼠给予等体积的双蒸水灌胃.给药前称量小鼠初始体重、摄食量和饮水量;给药期间,每两周逐只称量体重一次,同时称量并计算摄食量和饮水量.给药3个月后(8月龄)依次进行社会互动行为检测、旷场实验、Rota-rod实验和蔗糖饮水实验来观察PN-1对APP/PS1小鼠行为和精神症状的作用.结果 给药期间,相同月龄下各组小鼠间的体重、摄食和饮水均无显著性差异(P＞0.05).社会互动行为检测发现PN-1显著减少模型小鼠异常增多的攻击、追逐和嗅闻次数(P＜0.05).旷场实验结果显示,PN-1能够减少转基因小鼠水平和垂直方向的运动(P＜0.05)和高速运动时间(P＜0.05),同时减少其进入中心区域的探究次数(P＜0.05)并增加其修饰次数(P＜0.05).Rota-rod实验结果发现,PN-1能够增加转基因小鼠在滚轴上停留的时间(P＜0.05).蔗糖饮水实验结果显示,给予PN-1的转基因小鼠蔗糖偏嗜度有增高趋势,但与模型组相比并无显著性差异(P＞0.05).结论 PN-1能够改善APP/PS1双转基因小鼠的社会互动行为、减少过度增强的运动能力和探究行为,提高其耐力和平衡学习能力,并减轻其焦虑、烦躁、易激惹等精神症状.     

In-vivo and in-vitro effects of ethanol on mouse preimplantation embryos

In Exp. 1A, hybrid mice (N = 10) were provided with food and 25% (v/v) ethanol as the only source of liquid for 72 h, beginning at the detection of the copulatory plug (08:00 h, Day 1). Control mice received food and tap water. Food consumption (P less than 0.001) but not total caloric intake (P greater than 0.05) was less for the alcohol-treated mice than the controls. Ethanol-derived calories averaged 35% of caloric intake during the 72 h of treatment. Alcohol-treated animals showed a dramatic weight loss until Day 5 while controls gained weight (P less than 0.05). Ethanol consumption did not influence pregnancy rate, litter size or litter weight. In Exp. 1B, animals were treated as in Exp. 1A, but were killed at various times between 24:00 h, Day 1, and 08:00 h, Day 4. Trunk blood was used to determine haematocrit and serum to determine alcohol concentration. Haematocrit was greater (P less than 0.05) for all alcohol-treated mice than for controls at all time periods sampled except one. Dehydration was therefore probably responsible for the weight loss seen in Exps 1A and 1B. Average blood alcohol concentrations fluctuated with time of day and day of treatment. Average maximum concentration was 91.4 mg ethanol/100 ml serum. In Exp. 2, hybrid mouse 2-cell embryos were cultured in vitro in 0 or 0.1% ethanol (Exp. 2A) and 0 or 1.0% ethanol (Exp. 2B) for 8 days.(ABSTRACT TRUNCATED AT 250 WORDS)     

不同雌激素水平下大鼠颏舌肌肌电反应的研究

目的：通过比较不同雌激素水平下大鼠颏舌肌的肌电反应,探讨雌激素在预防及降低阻塞性睡眠呼吸暂停低通气综合征（OSAHS）发病过程中的作用机制。方法：选择30只6周龄SD大鼠建立不同雌激素水平模型,用电子称评估术前、术后和雌激素替代治疗后大鼠的体重变化;放射免疫法检测血清雌激素水平;电生理方法检测不同雌激素水平颏舌肌的肌电反应。结果：与假手术组（SHAM）相比,去势组（OVX）大鼠术后6周体重明显增加（P〈0．01）,雌激素替代治疗组（OVX＋E2）与SHAM组体重相当。血清雌激素检测结果显示OVX组雌激素水平最低,与SHAM组相比具有显著差异（P〈0．01）;OVX＋E2组雌激素水平高于OVX组（P〈0．01）,但仍未恢复到SHAM组水平。电生理检测结果显示,与SHAM组相比,OVX组颏舌肌肌电强度最低（P〈0．05）,OVX＋E2组颏舌肌的肌电强度显著高于OVX组（P〈0．05）,但仍低于SHAM组。结论：血清雌激素水平可以直接影响大鼠颏舌肌肌电强度．这可能是雌激素保护OSAHS的原因之一。     

Mouse inbred strain differences in ethanol drinking to intoxication

Recently, we described a simple procedure, Drinking in the Dark (DID), in which C57BL/6J mice self-administer ethanol to a blood ethanol concentration (BEC) above 1 mg/ml. The test consists of replacing the water with 20% ethanol in the home cage for 4 h early during the dark phase of the light/dark cycle. Three experiments were conducted to explore this high ethanol drinking model further. In experiment 1, a microanalysis of C57BL/6J behavior showed that the pattern of ethanol drinking was different from routine water intake. In experiment 2, drinking impaired performance of C57BL/6J on the accelerating rotarod and balance beam. In experiment 3, 12 inbred strains were screened to estimate genetic influences on DID and correlations with other traits. Large, reliable differences in intake and BEC were detected among the strains, with C57BL/6J showing the highest values. Strain means were positively correlated with intake and BEC in the standard (24 h) and a limited (4 h) two-bottle ethanol vs. water test, but BECs reached higher levels for DID. Strain mean correlations with other traits in the Mouse Phenome Project database supported previously reported genetic relationships of high ethanol drinking with low chronic ethanol withdrawal severity and low ethanol-conditioned taste aversion. We extend these findings by showing that the correlation estimates remain relatively unchanged even after correcting for phylogenetic relatedness among the strains, thus relaxing the assumption that the strain means are statistically independent. We discuss applications of the model for finding genes that predispose pharmacologically significant drinking in mice.     

Depression‐like symptoms of withdrawal in a genetic mouse model of binge methamphetamine intake

Binge methamphetamine (MA) users have higher MA consumption, relapse rates and depression‐like symptoms during early periods of withdrawal, compared with non‐binge users. The impact of varying durations of MA abstinence on depression‐like symptoms and on subsequent MA intake was examined in mice genetically prone to binge‐level MA consumption. Binge‐level MA intake was induced using a multiple‐bottle choice procedure in which mice were offered one water drinking tube and three tubes containing increasing concentrations of MA in water, or four water tubes (control group). In two studies, depression‐like symptoms were measured using a tail‐suspension test and a subsequent forced‐swim test, after forced abstinence of 6 and 30 hours from a 28‐day course of chronic MA intake. An additional study measured the same depression‐like symptoms, as well as MA intake, after prolonged abstinence of 1 and 2 weeks. MA high drinking mice and one of their progenitor strains DBA/2J escalated their MA intake with increasing MA concentration; however, MA high drinking mice consumed almost twice as much MA as DBA/2J mice. Depression‐like symptoms were significantly higher early after MA access was withdrawn, compared to levels in drug‐naïve controls, with more robust effects of MA withdrawal observed in MA high drinking than DBA/2J mice. When depression‐like symptoms were examined after 1 or 2 weeks of forced abstinence in MA high drinking mice, depression‐like symptoms dissipated, and subsequent MA intake was high. The MA high drinking genetic mouse model has strong face validity for human binge MA use and behavioral sequelae associated with abstinence.     

D-半乳糖诱导建立的小鼠多囊卵巢综合征模型

目的研究D-半乳糖诱导ICR中年雌性小鼠多囊卵巢综合征(PCOS)动物模型的卵巢形态学、性激素以及胰岛素水平变化,并探讨D-半乳糖引致小鼠PCOS的意义。方法以D-半乳糖腹腔注射20周龄ICR雌性小鼠8周,观察卵巢形态的变化,检测血糖值及动情周期排卵情况,并采用ELISA法测定血清胰岛素、雌二醇(E2)、促卵泡生长激素(FSH)、睾酮(T)水平。结果 D-半乳糖处理组小鼠的卵巢重量显著高于对照组(P<0.05),有80%(10/12)的单侧或双侧卵巢呈现多囊性扩张,卵巢闭锁增多及颗粒细胞层数减少,并表现为紊乱的动情周期,提示无排卵;与对照组比较,D-半乳糖组小鼠血清T、E2和空腹血糖水平明显升高(P<0.001),FSH水平下降(P<0.0001),空腹血胰岛素水平显著高于对照组(P<0.01),胰岛素敏感指数显著低于对照组(P<0.05)。结论使用D-半乳糖诱导小鼠PCOS模型,无论在影响血清性激素还是卵巢局部形态学改变方面都与临床表现相似,并存在胰岛素抵抗现象,符合PCOS的典型特征,可作为动物模型用于科学研究。     

Sweetened ethanol drinking during social isolation: enhanced intake,resistance to genetic heterogeneity and the emergence of a distinctive drinking pattern in adolescent mice

With its ease of availability during adolescence, sweetened ethanol (‘alcopops’) is consumed within many contexts. We asked here whether genetically based differences in social motivation are associated with how the adolescent social environment impacts voluntary ethanol intake. Mice with previously described differences in sociability (BALB/cJ, C57BL/6J, FVB/NJ and MSM/MsJ strains) were weaned into isolation or same‐sex pairs (postnatal day, PD, 21), and then given continuous access to two fluids on PDs 34–45: one containing water and the other containing an ascending series of saccharin‐sweetened ethanol (3–6–10%). Prior to the introduction of ethanol (PDs 30–33), increased water and food intake was detected in some of the isolation‐reared groups, and controls indicated that isolated mice also consumed more ‘saccharin‐only’ solution. Voluntary drinking of ‘ethanol‐only’ was also higher in a subset of the isolated groups on PDs 46–49. However, sweetened ethanol intake was increased in all isolated strain × sex combinations irrespective of genotype. Surprisingly, blood ethanol concentration (BEC) was not different between these isolate and socially housed groups 4 h into the dark phase. Using lickometer‐based measures of intake in FVB mice, we identified that a predominance of increased drinking during isolation transpired outside of the typical circadian consumption peak, occurring ≈8.5 h into the dark phase, with an associated difference in BEC. These findings collectively indicate that isolate housing leads to increased consumption of rewarding substances in adolescent mice independent of their genotype, and that for ethanol this may be because of when individuals drink during the circadian cycle.     

奥氮平诱导大鼠肥胖及其机制研究

目的建立奥氮平诱导的肥胖大鼠模型,并探讨其诱导肥胖的发生机制。方法 SD雌性大鼠20只,随机分为对照组和模型组,模型组大鼠每日黑暗时相前1h灌胃奥氮平(1.2mg/kg),对照组给予等容量蒸馏水。每周称体重1次,测饮水饮食量2次。给药7周时,利用SMART video-tracking system测定大鼠白天和黑暗时相的自主活动,然后处理大鼠,测体长,计算Lee's指数,称脂肪湿重,计算脂肪系数,采用高效液相色谱-电化学检测(HPLC-ECD)法测定大鼠下丘脑神经递质,用ELISA试剂盒测定血清瘦素(leptin)、脂联素(adiponectin,ADP)水平。结果模型组大鼠造模第2周至第7周时体重均明显高于对照组(P0.05或P0.01),饮食量明显增加(P0.01),黑暗时相平均速度、路程明显减少(P0.05),Lee's指数、脂肪湿重、脂肪系数明显升高(P0.05或P0.01),下丘脑5-HT、DA、DOPAC含量明显升高(P0.01或P0.05),血清leptin含量明显升高(P0.01),ADP含量明显降低(P0.01)。结论奥氮平(1.2mg/kg)增加动物摄食量,减少活动量而引起肥胖,此作用与下丘脑神经递质、瘦素和脂联素的调节有着密切联系。     

SD大鼠酒精性脂肪肝模型的监测分析

目的：通过血清生化指标和病理学的监测分析来建立标准的SD大鼠酒精性脂肪肝动物模型。方法：选取40只SD大鼠,随机分为两组,模型组采用直接饮酒法,于第8、12和20周时检测大鼠血清生化指标：丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、甘油三酯（TG）,并于第8、12周时随机采集5只大鼠肝组织,20周时采集剩余所有大鼠肝组织并进行病理学分析。结果：模型组于第8、12和20周时体重增长量均低于对照组（P〈0．01）,血清ALT、AST均高于对照组（P〈0．01）,第8周和12周时TG高于对照组（P〈0．01）。病理学结果显示肝组织从8周至20周呈现出酒精性脂肪肝、重度酒精性脂肪肝伴肝炎和酒精性肝纤维化等演变过程。结论：直接饮酒法可成功地复制出酒精性脂肪肝动物模型,通过监测分析可了解酒精性脂肪肝病变的整个过程,为今后建立酒精性脂肪肝和肝纤维化动物模型提供了理论参考。