抑郁症模型大鼠海马内小胶质细胞数量和炎症因子表达增加

目的 探讨慢性不可预知性应激(chronic unpredictable stress,CUS)抑郁症模型大鼠海马小胶质细胞总数量、活化小胶质细胞和炎症因子的变化情况.方法 选取6～8周龄的雄性Sprague-Dawley(SD)大鼠,在适应性饲养、糖水偏好基线调整及筛选后采用分层随机法分为空白对照组(n=19)和CUS干预组(n=48),给予CUS干预组大鼠5周的CUS干预,运用糖水偏好实验来评估两组大鼠的抑郁样行为,筛选出成模大鼠16只,即CUS模型组.采用免疫组织化学与体视学相结合的方法对两组大鼠海马各亚区小胶质细胞的总数量进行精确定量研究,运用免疫荧光方法评估大鼠海马各亚区活化小胶质细胞的密度,并采用实时定量PCR技术检测海马炎症因子的水平.结果 与空白对照组相比,CUS模型组大鼠的体质量明显下降(P＜0.01)、糖水偏好百分比显著降低(P＜0.01);CUS模型组大鼠海马CA1、CA2/3和DG区小胶质细胞的总数量较空白对照组均显著增加(P＜0.001,P=0.002,P=0.002);CUS模型组大鼠海马CA1、CA2/3和DG区活化小胶质细胞的密度和比例较空白对照组均显著增加(P=0.011,P=0.015,P＜0.001;P=0.018,P=0.019,P＜0.001);相对于空白对照组,CUS模型组大鼠海马炎症因子IL-1β和iNOS的mRNA表达量显著升高(P=0.012,P=0.020).结论 抑郁症模型大鼠海马各亚区内小胶质细胞总数量、活化小胶质细胞的密度和比例增加,炎症因子表达升高,表明海马小胶质细胞的改变可能参与抑郁症的病理过程.     

抗Lingo-1抗体对抑郁症伴认知障碍大鼠海马DG区少突胶质细胞作用的研究

目的：探讨抗Lingo-1抗体对抑郁症伴认知障碍大鼠海马齿状回（dentate gyrus,DG）区少突胶质细胞的作用。方法：4~6周清洁级雄性SD大鼠适应性喂养1周后,随机分为对照组（10只）和建模组（60只）,建立慢性不可预知性应激（chronic unpredictable stress,CUS）抑郁症模型,为期4周。利用糖水偏好实验筛选出成模大鼠（23只）,随机分为CUS组（12只）及Anti-Lingo-1组（11只）。运用Morris水迷宫评估对照组,CUS组和抗Lingo-1组的行为学水平,采用体视学方法计算各组大鼠海马DG区的少突胶质细胞数量。结果：应激4周和抗Lingo-1抗体治疗3周后,Morris水迷宫实验中,与对照组（3.4±0.2）相比,CUS组（2.4±0.2）大鼠Morris水迷宫第6天穿越平台次数明显降低（F=20.049, P=0.004）;与CUS组比较,抗Lingo-1组（4.3±0.3）大鼠穿台次数明显增加（F=20.049, P=0.000）。体视学研究结果表明,与对照组[（4.9±1.1）×104]比较,CUS组[（3.1±1.3）×104]大鼠海马DG区少突胶质细胞数量明显减少（F=8.747, P=0.026）;与CUS组比较,Anti-Lingo-1组[（6.1±1.1）×104]大鼠海马DG区少突胶质细胞数量明显增加（F=8.747, P=0.001）。结论：抗Lingo-1抗体可以改善抑郁症大鼠的认知障碍,抗Lingo-1抗体对抑郁症伴认知障碍大鼠海马DG区少突胶质细胞的作用可能是抗Lingo-1抗体改善抑郁症大鼠认知障碍的重要形态学基础之一。     

抑郁症易感性差异与海马CA3区及DG内树突棘数量变化的相关性研究

目的：探讨在慢性不可预知性应激（chronic unpredictable stress,CUS）模型中压力耐受大鼠海马结构CA3及海马齿状回（dentate gyrus,DG）内树突棘数量的改变情况,以期深入了解抑郁症发病的结构基础。方法：选用4~5周龄雄性sprague-dawley（SD）大鼠,将糖水偏好稳定的大鼠随机分为空白对照组和CUS造模组,造模组采取孤养并给予4周的CUS干预。根据糖水偏好结果筛选出CUS敏感组和CUS耐受组。利用免疫组织化学结合体视学方法对每组抽选出的5只大鼠海马结构CA3和DG内的树突棘数量进行精确的三维定量研究。结果：与空白对照组、CUS耐受组相比,CUS敏感组的糖水偏好百分比均明显下降（P=0.000,P=0.000）,而空白对照组与CUS耐受组的糖水偏好百分比无明显差异（P=0.262）;与空白对照组和CUS耐受组相比较,CUS敏感组大鼠海马结构CA3区内的树突棘数量明显下降（P=0.008,P=0.004）,CUS敏感组大鼠海马结构DG区内的树突棘数量也明显下降（P=0.001,P=0.001）;而在大鼠海马结构CA3及DG内,CUS耐受组与空白对照组的树突棘总数目无明显差异（P=0.656,P=0.950）。结论：CUS耐受组大鼠海马结构CA3及DG内树突棘的数量不受CUS干预的影响,提示海马结构内树突棘数量可能是抑郁症易感性差异的关键因素之一,为抑郁症的治疗提供了新的方向。     

11β-羟基类固醇脱氢酶-1在慢性温和应激抑郁大鼠海马组织中的表达

目的 应用慢性温和不可预知刺激( CUMS)建立抑郁症动物模型,探讨大鼠海马组织中11β-羟基类固醇脱氢酶-1(11β-HSD1)蛋白表达以及抑郁症的发病机制.方法 将24只Sprague-Dawley(SD)大鼠分为正常对照组和抑郁模型组,12只/组.建立CUMS模型后,分别采用体质量检测、糖水消耗和旷场试验评估大鼠行为学改变;采用实时荧光定量PCR方法检测大鼠海马组织11β-HSD1基因转录水平;采用组织免疫荧光和蛋白免疫印迹方法检测11 β-HSD1蛋白表达.结果 干预前,两组大鼠体质量和糖水消耗差异无统计学意义(P＞0.05).干预后,CUMS组大鼠体质量、糖水消耗、水平得分和垂直得分均较对照组显著降低(P＜ 0.05,P＜0.01);与对照组相比,CUMS组大鼠海马11β-HSD1 mRNA转录水平下降(31±9)％,蛋白表达显著降低(P＜0.05),11β-HSD1免疫阳性细胞数[(92±11)个]较对照组[(223±13)个]明显下降,差异具有统计学意义(P＜0.01).结论 慢性温和不可预知应激致大鼠产生抑郁行为并引起海马组织11 β-HSD1表达显著降低,其发生机制可能与体内11β-HSD1低表达及糖皮质激素代谢紊乱有关.     

焦虑模型大鼠下丘脑-垂体-肾上腺轴高反应性与糖皮质激素受体蛋白表达降低相关

目的 研究焦虑模型大鼠在应激条件时下丘脑-垂体-肾上腺(hypothalamus-pituitaryadrenal,HPA)轴呈高反应性是与轴本身功能亢进还是与反馈调节中糖皮质激素受体(glucocorticoid steroid receptor,GR)蛋白表达改变相关.方法 SD健康雄性大鼠随机分为对照组(n=20)和焦虑模型组(n=26).对照组正常饲养.采用不可预知的情绪应激方法建立大鼠焦虑模型.所有大鼠每周称量体质量.造模结束后,通过行为学鉴定造模是否成功.旷场和高架作为应激源刺激大鼠,测定两组大鼠血清中促肾上腺激素和皮质酮水平.Western blot检测GR蛋白在大鼠海马、下丘脑、垂体和肾上腺组织中的表达.结果 焦虑模型大鼠体质量增长率与对照组相比明显降低(P＜0.01).高架十字迷宫实验和旷场实验显示:与对照组相比,模型组大鼠进入开臂次数、开臂停留时间、进入开臂次数百分比和进入开臂时间百分比均显著降低(P＜0.01);总路程、中央活动路程百分比和中央活动时间百分比均显著降低(P ＜0.05,P＜0.01).在基础条件下,两组大鼠分泌促肾上腺激素和皮质酮差异无统计学意义(P＞0.05);而应激条件下,模型组大鼠分泌两种激素显著高于对照组(P＜0.01).与对照组比较,模型组在大鼠海马、下丘脑和肾上腺组织中GR蛋白表达显著降低(P ＜0.05,P＜0.01),而在垂体中表达差异无统计学意义(P＞0.05).结论 焦虑模型大鼠在应激条件下,HPA轴反应性增加与GR所介导的负反馈调节作用减弱有关.     

母鼠孕前慢性应激对成年雄性子代行为学和脑区单胺递质的影响

目的 研究母鼠孕前慢性应激对成年雄性子代行为学和脑内单胺类神经递质的影响.方法 16只成年雌性SD大鼠随机分为正常对照组和慢性不可预见性应激组(CUS),CUS组大鼠每天接受一种应激,共21d,正常对照组不接受任何应激.应激结束后10 d,2组大鼠均与同种SD雄性大鼠合笼,以成年2月龄雄性子代作为研究对象.用糖水消耗实验测量快感缺失,Morris水迷宫检测空间记忆能力,高效液相色谱法测量海马、下丘脑和前额皮质单胺递质的含量.结果 糖水消耗实验示正常对照组子代的糖水消耗量和糖水消耗百分比均显著高于CUS组子代[糖水消耗量:(10.23±4.12)g,(6.48±3.19)g;糖水消耗百分比:(85.43±20.15)%,(60.98±24.65)%](P＜0.05).Morris水迷宫检测示2组的逃避潜伏期无差异,但空间探索测试中正常对照组子代[(4.17±2.29)次]穿越平台的次数明显多CUS组子代[(1.64±1.69)次](P＜0.05).CUS组子代[(500.17±80.94)ng/g脑组织]下丘脑5-羟色胺的含量低于正常对照组子代[(569.63±50.91)ng/g脑组织](P＜0.05),而CUS组子代[(2315.01±1397.12)ng/g脑组织]海马去甲肾上腺素的含量却要高于正常对照组子代[(907.56±207.27)ng/g脑组织](P＜0.05).结论 母鼠孕前慢性应激或抑郁会造成成年雄性子代的快感缺失和空间记忆力下降,以及脑内单胺类神经递质异常.     

压力耐受大鼠和压力易感大鼠大脑白质及白质内有髓神经纤维的体视学研究

目的 探讨在慢性不可预知性应激(chronic unpredictable stress,CUS)后压力耐受大鼠大脑白质体积及白质内有髓神经纤维总体积的改变,分析对压力的耐受能力是否与大脑白质的改变有关.方法 选用50只4～5周龄雄性Sprague-Dawley (SD)大鼠,采用完全随机法分为空白对照组和模型组.模型组的大鼠在给予4周的CUS之后,根据糖水偏好实验(sucrose preference test,SPT)的结果筛选出压力易感组和压力耐受组.采用旷场实验(open field test,OFT)评估各组的行为学水平,运用体视学方法计算各组大鼠白质体积和白质内有髓神经纤维的体积.结果 压力易感组的蔗糖偏好百分比显著低于空白对照组和压力耐受组(P＜0.01).压力耐受组OFT总成绩显著优于空白对照组和压力易感组(P＜0.01).压力耐受组的白质体积显著性高于压力易感组(P＜0.01),但与空白对照组比较,差异没有统计学意义(P＞0.05).压力耐受组白质的有髓神经纤维总体积显著性高于压力易感组(P＜0.01),与空白对照组相比差异没有统计学意义(P＞0.05).结论 白质和白质内有髓神经纤维的改变可能与抑郁易感性差异存在关系.     

p-Tau蛋白在抑郁症大鼠海马组织中的表达

目的:观察抑郁症大鼠海马组织中磷酸化微管相关蛋白Tau(p-Tau)的表达水平,探讨p-Tau与抑郁症的关系。方法:40只大鼠随机分为对照组(n=20)和模型组(n=20),模型组大鼠采用慢性不可预见性温和应激(CUMS)建立大鼠抑郁症模型,对照组大鼠每天抓取1次。分别采用糖水偏好实验、旷场实验和Morris水迷宫实验检测对照组和模型组大鼠行为学表现;尼氏染色观察大鼠海马神经元形态学;对照组和模型组造模后1、7、14和28 d分批处死大鼠,采用Western blotting法检测大鼠海马组织中p-Tau蛋白表达水平。结果:糖水偏好实验,模型组大鼠糖水消耗量和糖水偏好百分比低于对照组(P<0.01);旷场实验,模型组大鼠行走总路程、中央活动时间、直立次数和修饰行为次数少于对照组(P<0.01);Morris水迷宫实验,模型组大鼠平均逃避潜伏期长于对照组(P<0.01);CUMS后1 d,模型组大鼠海马组织中p-Tau蛋白表达水平低于对照组(P<0.01),7 d后开始高于对照组(P<0.05),14 d时大鼠海马组织中p-Tau蛋白表达水平最高(P<0.01)。结论:抑郁模型大鼠海马组织中p-Tau蛋白表达水平先降低后增高,这可能影响微管的稳定性,破坏细胞骨架稳态,从而导致海马神经元的结构改变。     

氟西汀对抑郁模型大鼠海马CA1区少突胶质细胞作用的研究

目的：探讨抗抑郁药物氟西汀对抑郁症慢性不可预知性应激（chronic unpredictable stress,CUS）模型大鼠海马CA1区内CNPase+少突胶质细胞的作用。方法：选用青年雄性Sprague Dawley（SD）大鼠（4~6周龄）,随机分为对照组（12只）和模型组（38只）,给予模型组大鼠连续4周的CUS干预。随后依据大鼠的糖水偏好百分比筛选出模大鼠,随机分为CUS组（12只）和CUS+fluoxetine组（FLX组）（12只）,第5~7周CUS组和FLX组继续给予慢性应激,同时FLX组大鼠给予5 mg/（kg·d）氟西汀腹腔注射,对照组和CUS组给予等量生理盐水腹腔注射。干预结束后利用免疫组织化学方法结合现代体视学对大鼠海马CA1区CNPase+少突胶质细胞的数量进行精确的三维定量研究。结果：实验发现,CUS模型组大鼠的体质量（251.4±15.9） g较对照组（323.3±25.9） g明显下降（P=0.00）,但与FLX组大鼠的体质量（257.9±22.7） g相比无差异（P=0.473）。CUS组大鼠的糖水偏好百分比（62.0±14.2）%明显低于对照组（89.2±4.8）%（P=0.000）及FLX组（78.2±12.8）%（P=0.020）。CUS组大鼠海马CA1区CNPase+细胞数量（18 650.7±1 812.0）明显低于对照组（33 606.9±4 471.4）（P=0.007）及FLX组（29 080.7±2 877.5）（P=0.042）。结论：大鼠海马CA1区内少突胶质细胞在抑郁症发病过程中可能起着重要作用,氟西汀治疗可防止抑郁症模型大鼠海马CA1区的CNPase+少突胶质细胞的丢失。本研究结果为探索新的抗抑郁策略提供了形态学基础。     

慢性应激对老龄雌性大鼠学习记忆和海马齿状回甘氨酸水平的影响

[目的]探讨慢性不可预见性应激(CUS)对老龄雌性大鼠学习记忆和海马齿状回(DG)甘氨酸水平的影响.[方法]取20月龄SD雌性大鼠随机分为对照组和CUS组,利用多种刺激随机应用法制作CUS大鼠模型(每天1种刺激,连续30d).通过Morris水迷宫实验观察大鼠空间学习和记忆能力,应用脑部微量透析法和高效液相色谱法测定海马DG甘氨酸水平,采用ELISA法测定大鼠血清中皮质酮水平.[结果]CUS组血清中皮质酮水平显著高于对照组(P<0.05).Morris水迷宫实验结果显示,与对照组比较,CUS组定位航行实验中第1,4d的逃避潜伏期明显延长(P<0.05),空间探索实验中第5d的目标象限游泳时间明显减少(P<0.05).与实验前比较,对照组Morris水迷宫实验第2,5d海马DG甘氨酸水平明显升高(P<0.05),而CUS组海马DG甘氨酸水平未见发生变化(P>0.05).[结论]CUS降低老龄雌性大鼠空间学习和记忆能力,可能机制认为与大鼠海马DG甘氨酸水平降低有关系.     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…     

Development on Adjustable Calibration Marker for Shock Wave Focus

Shock wave lithotripsy （SWL） is a treatment of choice for upper urinary stones. However, this procedure is inappropriate for obese patients because the focus is often unable to reach the target owing to the limited focal distance in shock wave source. Although treating such patients in a blast path may increase the application length of shock wave source, it＇s difficult to find this path on the lithotripter monitor. For this reason, we invented an adjustable calibration marker in order to set an effective focus in the shock wave hath.     

Study on the TCM Pathogenesis of Angiopathic Complications of Type II Diabetes

Excess production of reactive oxygen species(ROS)of mitochondrion mediated by hyperglycemia is the common pathogenesis of angiopathic complications of diabetes.TCM holds that the damp from the dysfunction of spleen.kidney and liver is the causative factor of complications of diabetes.This is similar to the mechanism of Ros resulting in angiopathic complications of diabetes.When the angiopathic complications of type II diabetes mellitus(T2DM)are difierentiated as caused by turbid damp in TCM can be explained as ROS.Since the obstruction of pathogenic damp in channels and collaterals is said to be the main pathogenesis,the treating principle should be dissolving the damp to remove the obstruction.     

Leptin, Ghrelin and TNF-α before and after Hypo-caloric Traditional Chinese Diet and Auricular Acupuncture

INTRODUCTION Obesity is a complex emergent problem, which can be possibly solved not only by the diet but also by the life style and promotion of a constant physical exercise. 1, 2 No doubt careful attentions must be given to the nutritional condition of obese people, the dietary habits, the somatic build (i.e. distribution of fat mass) and the organic functions linked to formation of the fat mass. All the parameters should be constantly monitored before, during and after a diet treatment. 3, 4, 5     

Relationship between Dysglycemia and Carotid Atherosclerosis in Tibetan Population

People with dysglycemia are at high risk for atherosclerotic diseases. This study aims at investigating the atherosclerotic vascular damage in dysglycemia and its metabolic origin in Tibetan population.     

Acupuncture Combined with Spinal Tui Na for Treatment of Primary Dysmenorrhea in 30 Cases

Objective: To observe the therapeutic effects in acupunture treatment of primary dysmenorrhea combined with spinal Tui Na, and study its mechanism. Methods: Thirty cases of the treatment group were treated by acupuncture combined with spinal Tui Na, and thirty cases in the control group were treated by routine acupuncture. Results: The total effective rate was 93.3% in the treatment group, and 73.3% in the control group, with a significant difference between the two groups (P<0.05). Conclusions: Acupuncture combined with spinal Tui Na has good prospects for treatment of primary dysmenorrhea.     

Luo Lingjie's Experience in Treating Chronic Nephropathy

In treating chronic nephropathy,Luo Lingjie,a chief physician,pays attention to regulating the balance between yin and yang,treating infection if present,and removing pathogenic factors.He prescribes gentle drugs and uses carefully strongly warming-tonifying ones,emphasizes the importance of persuading the patient to persist in treatment with medication and nurse one's health for recuperation,and is good at combined use of TCM and western medicine therapy and brings the merits of various therapies into full play,with obvious theraoeutic effects.     

Dr.Zhang Ren's Experience in the Acupuncture Treatment of Different Diseases with the Same Therapeutic Principle

Dr.Zhang Ren,the chief physician,is the chairman of Shanghai Acupuncture and Moxibustion Association.Having been engaged in medicine for about 40 years,he is experienced in treating various intractable diseases.In his long years of clinical practice,he advocates taking the TCM differentiation as the basis to seek for the acupuncture method for treatment of modern intractable diseases.The author of this essay had the fortune to follow Dr.Zhang in study.The following is a summary of Dr.Zhang's experience in the acupuncture treatment for different intractable diseases with the same therapeutic principle.