Nerve protective effect of Baicalin on newborn HIBD rats

Objetive:To investigate the nerve protective effect and mechanism of baicalin on newborn rats with hypoxic ischemic brain damage(HIBD).Methods:A total of 64 SD newborn rats were randomlu divided into control group.model group.nerve growth factor group and baicalin group.with 16 in each group.Left carotid artery ligation method was adopted to establish the HIBD model except fou in control group,which was treatde with intraperitoneal injection of salin e10mL/kg for 3 d.After oxygen recovery on hypoxia ischemia rats.intraperitoneal injectionof salin 10mL/kg was adopted in model group for 3 d.Intraperitoneal injection of nerve growth factor injection50μg/kg per day was adopted in nerve growth factor group for 3 d:intraperitoneal injection of radix scutellariae 16mg/kg per day was adopted in baicalin group for 3 d after modeeling.Four rats of each group were sacrificed at Day 1,2,3,7 for microscopic observation of pathological morphological changes in brain tissus aften HE staining,S-P immunohistochemical method was used for observation of Fas and FasL expression in brain cells.Results:Neat structure of cells was observed in control group;edema cells in disordered arrangement was observed in model group,with some cells necrosis and cavity change;tissue injury in nerve growth factor group and baicalin group was significantly lighter than that in model group;Fas and FasL expression in model group,nerve growth factor group and baicalin group were significantiy higher than that in control group at different time points(P0.05):Fas and FasL expression in nerve growth factor group and baicalin group were significantly lower than that in model group at different time points(P0.05):There was no statistical diggerence of Fas,FasL expression at each time point between nerve growth factor group and baicalin group(P0.05).Conclusions:Baicalin can reduce expression of Fas and FasL in HIBD rats,inhibit apoptosis of nerve cells,thus achieve the protective effect on HIBD rat nerves.     

间歇性低氧预处理对慢性缺血心脏保护作用的实验研究

目的:采用冠状动脉左前降支部分结扎的方法复制慢性心肌缺血的动物模型,观察间歇性低压低氧预处理对缺血心脏泵功能的保护作用。方法:成年雄性新西兰家兔22只,体质量2.02.5 kg,随机分为2大组:对照组（C组,n=11）和间歇性低压低氧预处理组（H组,n=11）。两组动物均先进行冠状动脉左前降支部分结扎,7 d手术恢复期后,H组动物开始间歇性低压低氧预处理（5000 m,6 h/d,连续7 d者为H1组,42 d者为H2组）,C组动物分为C1、C2组常规饲养（实验时间分别与H1、H2组相同）。按计划完成实验后,测定各组动物心率（HR）、左室收缩期内压最大变化速率（LVdp/dtm ax）及左室舒张期内压最大变化速率（-LVdp/dtm ax）,然后给予急性缺氧,重复测定上述指标,并与急性缺氧前所测相应各值比较,观察各组动物对急性缺氧的耐受性。同时观察各组动物的心肌细胞的超微结构及心肌VEGF mRNA的表达。结果:急性缺氧时,H2组HR的下降程度显著小于其它3组（P<0.01）;LVdp/dtm ax的下降程度显著小于C2组（8.5%vs30.5%,P<0.01）。恢复常氧后,H2组的LVdp/dtm ax恢复程度显著优于C2组（下降率为0.9%vs18.6%,P<0.01）;-LVdp/dtm ax恢复程度亦优于C2组及其它2组（P<0.05）。H2组动物心肌线粒体数量增加。经低氧预处理后心肌组织的血管内皮生长因子（VEGF）mRNA表达明显增高。结论:长期间歇性低压低氧预处理能增强缺血心脏对急性缺氧的耐受性,对慢性局灶性缺血心脏有保护作用。     

妥泰治疗新生大鼠缺氧缺血性脑水肿的实验研究

将32只7日龄Wister大鼠随机分为正常对照组（8只）、缺氧缺血组（12只）、妥泰治疗组（12只）。缺氧缺血后即刻经胃管注入妥泰或生理盐水,24小时后检测各组脑含水量、伊文思蓝（EB）含量及脑组织钠、钙含量。结果显示,缺氧缺血组脑含水量、EB含量及钠、钙含量明显高于对照组（P＜0．01）;妥泰治疗组脑含水量、EB含量及总钠含量明显低于缺氧缺血组（P＜0．01、0．05、0．05）。证实妥泰能减轻缺氧缺血后脑组织中钠蓄积,降低血脑屏障的通透性,减轻脑水肿。     

尼莫地平对脑出血后缺血性脑损害保护作用的研究

目的探讨脑出血后继发性缺血性脑损害机制以及尼莫地平对脑出血后继发性缺血性脑损害的保护作用。方法60例脑出血患者随机分为尼莫地平组(30例)与常规治疗组(30例),在治疗前后用单光子发射型计算机断层显像(SPECT)观察原发灶缺血体积,血肿周围及脑部其他区域的局部脑血流量(rCBF)变化。结果尼莫地平组和常规治疗组治疗后原发灶缺血的体积明显缩小,原发灶缺血体积减少值尼莫地平组明显高于常规治疗组(P<0.01)。治疗后原发灶及远隔部位缺血灶rCBF增加值尼莫地平组明显高于常规治疗组(P<0.01)。结论脑出血后血肿周围及远隔区域可出现广泛的rCBF下降,血肿周围可能存在缺血半暗带。尼莫地平治疗脑出血有确切疗效,可改善局部脑缺血。     

G-CSF对压力超负荷引起的心室重构和心力衰竭的影响

目的探讨粒细胞集落刺激因子(granulocyte colony stimulating factor,G-CSF)对压力超负荷引起的心室重构和心力衰竭发生发展的影响及其机制。方法实验动物分成7组:PBS组小鼠(PBS组)、替米沙坦组小鼠(ST组)、G-CSF(A)组小鼠(GA组)、G-CSF(B)组小鼠(GB组)、G-CSF 替米沙坦组小鼠(GT组)、替米沙坦 G-CSF组小鼠(TG组)和假手术组小鼠(sham组)。小鼠经缩窄升主动脉后,在不同时间皮下注射G-CSF或(和)替米沙坦,每周做心脏超声检测心脏功能和形态变化,分别于第1周、2周和4周末测量有侧颈动脉压后取材,用HE染色、Masson三色染色观察心脏形态变化,用Western blotting检测血管内皮生长因子(vascular endothelial growth factor,VEGF)和RT-PCR检测缺氧诱导因子1(hypoxia-inducible factorl,HIF-1)、p53mRNA的表达情况。结果(1)在0～14 d,缩窄升主动脉的小鼠心室擘厚度值逐渐升高达高峰,14～28 d PBS组厚度逐渐降低,同时伴有左室射血分数的下降,而给予G-CSF皮下注射的小鼠未见有降低,也未见有射血分数的下降;(2)同PBS组比较,VEGF蛋白、HIF-1mRNA表达存给予G-CSF皮下注射的小鼠显著升高,而p53mRNA表达、心脏纤维化程度和死亡率在给予G-CSF组显著降低。结论G-CSF通过调控血管新生,改善了压力超负荷引起的心室重构和心力衰竭,其中调控HIF-1的表达可能起着重要的作用。     

粒细胞集落刺激因子对阿尔茨海默病大鼠脑内炎症的影响

目的探讨粒细胞集落刺激因子(G-CSF)治疗阿尔茨海默病(AD)大鼠对脑内炎症反应的影响。方法 54只Wistar雄性大鼠(3~4个月龄),随机选取18只作为正常组、36只制作AD大鼠模型成功后采用随机数字表法各选取18只分别作为治疗组、模型组;模型组和正常组采用HE染色法对大脑皮层组织进行观察,治疗组给予G-GCS(0.3 ml·kg-1·d-1),模型组和正常组分别给予等量磷酸盐缓冲液(PBS)注射,又分别于第7、14、21天进行相关指标的检测并进行组间比较。结果正常组治疗第7、14、21天的大脑皮层细胞IL-1β染色光密度值均显著低于模型组、治疗组(P0.05),治疗组治疗14、21 d后大脑皮层细胞IL-1β染色光密度值低于模型组(P0.05)。正常组治疗第7、14、21天的大脑皮层细胞TNF-α染色光密度值均显著低于模型组、治疗组(P0.05),治疗组治疗14、21 d后大脑皮层细胞TNF-α染色光密度值低于模型组(P0.05)。结论 AD大鼠对脑内炎症反应作用显著增强,G-CSF可以有效降低AD大鼠的炎症反应作用,对大鼠大脑皮层细胞具有一定的保护作用。     

Early protective effect of ischemic preconditioning on small intestinal graft in rats

AIM: To investigate the early protective effect of ischemic preconditioning on small intestinal graft in rats.METHODS: SD rats were randomly divided into the following groups: sham operation group (S group, n=6),small bowel transplantation group (SBT group, n=12),ischemic preconditioning plus small bowel transplantation group (ISBT group, n=12). Heterotopic SBT was performed with a technique modified from that described by Monchik et al.When the graft was revascularized successfully and reperfused for 1 h, samples were obtained from the different groups. Laminin was analyzed with immunohistochemical staining. Quantitative analysis of laminin positive signals was performed using image acquiring analysis system. Apoptotic epithelia of small intestinal graft were detected by the TdT-mediated dUTP nick end labeling method. The morphological change of epithelial basement membrane was observed by transmission electron microscopy.RESULTS: The mean optical density value of laminin positive signals was 39.52±2.60, 13.53±0.44, 25.40±1.79,respectively, in S, SBT and ISBT groups. The average optical density value of laminin positive products in SBT group was sharply lower than that in S group (P＜0.05). However,the mean optical density value of laminin positive products in ISBT group was significantly higher than that in SBT group (P＜0.05). The apoptotic index (AI) in S, SBT and ISBT group was 2.2±0.83,30.8±3.2, 13.2±2.86, respectively.The AI in SBT group was significantly higher than that in S group (P＜0.05), and AI in ISBT group was sharply lower than that in SBT group (P＜0.05). On transmission electron microscopy, the epithelial basement membrane in S group stayed normal, but in SBT group it became disrupted and collapsed, even disappeared. The lesion of epithelial basement membrane in ISBT group was slighter compared with that in SBT group.CONCLUSION: Ischemic preconditioning has an early protective effect on epithelial cells and extracellur matrix of small intestinal graft. Inhibition of epithelial cell apoptosis may be one of the mechanisms of ischemic preconditioning.     

The effect of continuous G-CSF application in human cyclic neutropenia: a model analysis

Human cyclic neutropenia (CN) is a rare haematological disorder characterized by oscillations of blood neutrophils at subnormal levels with a stable period of approximately 21 d. During the phase of severe neutropenia (neutrophils <250 cells/yul), which last 4–10 d, the patients are endangered by serious infections. Several authors report that continuous G-CSF application can elevate the blood neutrophils to such a level that the risk of infections is significantly reduced. Although the characteristic cycles are not eliminated by G-CSF, the period of the oscillations is shortened to 12–14 d. Based on a previously proposed computer-simulation model of human CN, the effects of continuous G-CSF application on CN are studied. It is shown how the known different cell-kinetic effects of G-CSF on granulopoiesis explain the clinical data in CN. The reduced length of the cycles emerges as a result of the transit time reduction of the post-mitotic granulopoietic cells by G-CSF. The measured increase of the neutrophil maxima is reproduced by the additional mitoses of the immature granulopoietic bone marrow cells induced by G-CSF. The slight elevation of the neutrophil nadirs can be attributed to a weak effect of G-CSF on the assumed underlying defect in CN (an abnormally small variance of the granulopoietic bone-marrow transit time).     

中药虎杖对大鼠肝脏缺血性损伤保护的形态学观察

目的研究中药虎杖煎剂在治疗大鼠肝脏缺血性损伤后肝组织的病理学改变,证实该药对急性肝脏缺血性损伤有治疗作用.方法建立大鼠常温下肝门完全阻断的模型,观察肝脏缺血损伤后虎杖组和普食组在不同的时间段肝组织的病理学改变.结果通过光镜和电镜发现,术后1 d普食组与虎杖组肝细胞肿胀,结构破坏,肝窦内皮细胞孔隙加大,内皮破坏,内皮之间可见孔道.术后4 d普食组肝小叶结构仍破坏,线粒体肿胀,颗粒变性.而虎杖组未见肝细胞坏死改变,细胞膜特化部分如桥粒、毛细胆管区微绒毛有轻微破坏.术后7 d普食组肝细胞变性仍可见,线粒体轻度肿胀,基质变化,膜结构欠清楚,粗面内质网欠规则.而虎杖组肝细胞基本恢复正常形态.结论虎杖煎剂具有改善损伤肝组织的微循环,抑制白细胞、血小板与肝脏内皮细胞的粘附,达到促进肝细胞再生、修复损伤的能力.为临床上肝脏外科围手术期的应用奠定了病理学基础.     

整体低氧预处理对大鼠肺缺血再灌注损伤的保护作用及机制

目的探讨整体低氧预处理（WHPC）对肺缺血再灌注（I/R）损伤的保护作用及可能机制。方法将50只肺I/R损伤模型大鼠随机分为5组。模型组不干预;制模前30 min WHPC组行WHPC;5-羟癸酸（5-HD）＋WH-PC组制模前30 min静注5-HD 10 mg/kg、行WHPC;二氮嗪（DE）组制模前30 min腹腔注入DE 10 mg/kg;5-HD＋DE组制模前30 min静注5-HD 10 mg/kg,15 min后腹腔注射DE 10 mg/kg。观察各组肺组织病理形态学变化、肺湿/干重比变化,采用分光光度计比色法检测肺组织丙二醛（MDA）含量及髓过氧化物酶（MPO）活性,采用TUNEL法检测肺组织细胞凋亡指数（AI）变化。与对照组（假手术,不行干预）比较。结果与对照组比较,模型组肺组织出现明显损伤性形态学改变,肺湿/干重明显增加,肺组织MDA含量和MPO活性明显增高,AI亦明显增高。与模型组比较,WHPC组和DE组肺组织损伤性病理改变明显减轻,肺湿/干重明显降低,MDA含量、MPO活性及AI亦均明显降低。结论 WHPC对大鼠肺缺血再灌注损伤有明显保护作用,其机制可能为WHPC促使线粒体ATP敏感钾通道开放。     

抗高血压因子对心肌缺血损伤的保护作用

对SD大鼠皮下注射异丙肾上腺素（85mg／kg）造成心肌缺血损伤模型后，观察其心肌含水量、心肌酶（CK、LDH）释放量、心肌钙含量和丙二醛含量及心肌病理损伤程度，结果上述指标显著增加（P＜0．01），如同时腹腔注射抗高血压因子（3．0mg／kg）则上述指标均有不同程度减轻（P＜0．05）。提示抗高血压因子对异丙肾上腺素性心肌缺血损伤具有明显的保护作用，其机理主要是与抗高血压因子防止心肌细胞钙超载和抑制氧自由基产物生成有关。     

G-CSF和高脂喂养对兔血小板功能影响的实验研究

目的探讨G-CSF在应用于干细胞动员治疗心血管疾病时对血小板功能的影响。方法16只新两兰大白兔随机分为普通和高脂喂养2组，予G—CSF皮下注射5日，用药前后分别测定PLT、MPV、PDW、P—LCR、TXB2、P选择素等血小板相关指标，并采用全血CD41-FITC／CD62P、CD63-PE荧光抗体双标流式分析法进行验证。结果用药后普通喂养组除PLT计数外上述各项指标与基础状态相比均增高。但高脂喂养组除P—LCR外，其他指标无显著变化。而用药前后者的P-LCR、TXB，高于前者。结论G—CSF在作用高峰能引发血小板功能的活化，其机制可能与应激反应有关。高血脂本身就有激活血小板的作用。全血细胞流式分析是检测血小板活化的较灵敏方法。     

单硝酸异山梨醇乙酰阿魏酰胺的设计合成及对大鼠缺血心脏保护作用的研究

目的:研制单硝酸异山梨醇乙酰阿魏酰胺（AcFA-201）,并与阿魏酸钠（SF）、单硝酸异山梨醇酯（ISMN）和单硝酸异山梨醇乙酰阿魏酸酯（AFI）比较其对心肌缺血/再灌注（MI/R）大鼠心肌的保护作用。同时比较AcFA-201与AFI在模拟胃液中的稳定性。方法: 先将ISMN的羟基转化为胺基,再与乙酰化阿魏酰氯反应,生成新化合物AcFA-201。常规建立大鼠MI/R（30 min/3 h）模型,随机给予SF、ISMN、AFI或AcFA-201药物治疗。观察各组大鼠灌注末心功能恢复的情况,同时测定血清肌酸激酶（CK）、乳酸脱氢酶（LDH）、超氧化物歧化酶活性（SOD）、过氧化氢（H2O2）与丙二醛（MDA）的水平及NO的含量。结果: 合成路线可行,化合物AcFA-201的化学产率为81.8%。模拟胃液中的稳定性研究结果表明,AFI在给药10 min后,原药剩余很少,30 min完全消失;而AcFA-201在180 min后,基本保持初始给药浓度。与SF、ISMN治疗组相比,AcFA-201治疗组左室发展压、左室等容收缩压/舒张期压力上升或下降最大速率（±dp/dtmax）显著提高(n=8,P<0.05)。血清CK、LDH的活性和H2O2、MDA的含量降低而NO含量显著升高(n=8,P<0.05或P<0.01);与AFI组相比,AcFA-201组各项指标均无显著性差异。结论: AcFA-201对MI/R损伤大鼠的心肌具有保护作用,其作用比SF、ISMN强,与AFI没有显著性差异。AcFA-201在模拟胃液中的稳定性明显优于AFI,更适合口服药物的研发。     

Prolonged protective effect of propranolol on hypoxic heart muscle

To assess whether the in vivo administration of propranolol protects heart muscle against the deleterious effects of hypoxia and to establish how long the protection persists after cessation of therapy, rabbits were given propranolol, 2.0 mg/kg subcutaneously twice daily for 5 to 6 days. This dose regimen was used to provide plasma levels comparable with those obtained clinically. The hearts were isolated and perfused under either aerobic (partial pressure of oxygen [PO₂]greater than 600 mm Hg) or hypoxic (PO₂ less than 6 mm Hg) conditions. Heart rate was kept constant. Coronary effluent was collected and assayed for creatine klnase (CK) activity and myoglobin content. Resting and peak systolic tension was monitored and, after 60 minutes of perfusion, the mitochondria were harvested and assayed for respiratory activity (atoms oxygen used/mg mitochondrial protein per min [QO₂], respiratory control index [RCI]and nmol adenosine dlphosphate used/n atoms oxygen consumed [$\text{ADP}\text{O}{}_2$ ratio]) and Ca⁺⁺-accumulatlng activity. The control rabbit hearts responded to the hypoxia-perfusion state with release of CK and myoglobin and an increase in resting tension. Mitochondrial QO₂ and RCI were significantly depressed. Mitochondrial Ca⁺⁺-accumulating activity was enhanced. The propranolol-treated rabbit hearts were protected in that they released CK and myoglobin more slowly and had a lower rate of rise of resting tension. Mitochondrial respiratory activity (QO₂ and RCI) was also better maintained, and the mitochondria accumulated Ca⁺⁺ at a relatively slow rate. This protective effect of propranolol pretreatment was not accompanied by a changed tissue level of adenosine triphosphate, creatine phosphate or glycogen.The protective effect of propranolol persisted for up to 72 hours after the last dose of propranolol, and hence was present when beta adrenoceptor blockade was no longer effective. These results support the hypothesis that there may be secondary consequences of beta blockade.     

Effects of in vivo administration of G-CSF on neutrophil and eosinophil adhesion

The effect in vivo of G-CSF on neutrophil and eosinophil adhesion was studied after subcutaneous administration to six healthy individuals of human recombinant glycosylated G-CSF (lenograstim) (3 μg/kg) for 6 consecutive days. Basal adhesion and adhesion to E-selectin, VCAM-1 and ICAM-1 of neutrophil and eosinophil granulocytes were measured selectively. During G-CSF administration neutrophil basal adhesion increased from 7.4 ± 3.9% (mean ± SD) to 55.8 ± 12.9% and 23.2 ± 4.4%, 4 and 7 d, respectively, after start of the administration. At the same time points eosinophil basal adhesion increased from 7.1 ± 2.4% to 37.7 ± 6.1% and 13.1 ± 5.3%, respectively. When adhesion was measured in the presence of Mn²⁺, which increases the functional activity of integrins, an even higher increase of neutrophil and eosinophil basal adhesion was noted 4 and 7 d, respectively, after start of G-CSF administration. In parallel with the enhanced basal adhesion neutrophil adhesion to E-selectin and ICAM-1 and eosinophil adhesion to E-selectin, VCAM-1 and ICAM-1 were significantly (P < 0.05) increased after 4 d of G-CSF administration as was neutrophil cell surface expression of CD11b and CD18. In vitro G-CSF induced minimal changes of granulocyte basal adhesion and inhibition of the adhesion to E-selectin. 10 ng/ml TNFα significantly increased neutrophil and eosinophil basal adhesion and adhesion to VCAM-1 and ICAM-1. In summary, administration of G-CSF to healthy subjects induced enhanced adhesion of neutrophil and eosinophil granulocytes, probably mediated by an increase of the functional capacity of β₁- and β₂-integrins. The induction of increased levels of TNFα might be one mechanism behind the in vivo effect of G-CSF administration.     

清脑益元汤对大鼠脑缺血损伤Nestin、NGF表达的影响

目的研究清脑益元汤对大鼠脑缺血损伤后巢蛋白(Nestin)、神经生长因子(NGF)表达的影响,探究清脑益元汤对缺血性脑损伤神经元保护作用的部分机制。方法将192只健康SD大鼠随机分为两大组,每大组再分为4个亚组:空白组(n=6)、假手术组(n=30)、模型组(n=30)、清脑益元汤组(n=30)。采用改良的Longa线栓法制备大鼠急性脑缺血损伤模型,除空白组外,假手术组、模型组及清脑益元组按缺血损伤后1 d、3 d、7 d、14 d、28 d 5个取材时间点分为5个亚组。造模成功后取大鼠缺血侧脑组织,采用免疫组化法检测大鼠缺血侧皮质区Nestin、NGF表达,采用实时荧光定量PCR(Real-Time PCR)法检测大鼠缺血侧皮质区Nestin、NGF mRNA表达。结果(1)免疫组化法:与假手术组相比,模型组、清脑益元组在缺血侧Nestin、NGF阳性细胞明显增多(P<0.01,P<0.01);与模型组相比,清脑益元组Nestin、NGF阳性细胞表达明显增多(P<0.01,P<0.05);(2)Real-Time PCR法:与假手术组相比,模型组、清脑益元汤组大鼠脑组织缺血侧皮质区Nestin、NGF mRNA表达量增加(P<0.01,P<0.01);与模型组相比,清脑益元汤组大鼠脑组织缺血侧皮质区Nestin、NGF mRNA表达量升高(P<0.01,P<0.05)。结论清脑益元汤可能通过上调脑缺血损伤后Nestin、NGF蛋白及mRNA表达,促进脑组织损伤修复、保护神经元,进而发挥脑保护的作用。     

Safety and efficacy profile of G-CSF therapy in patients with acute on chronic liver failure

BACKGROUND/AIM: We aimed to evaluate safety and efficacy of granulocyte-colony stimulating factor treatment in patients with acute on chronic liver failure and the effect of granulocyte-colony stimulating factor on the expression level of CXCR4, vascular endothelial growth factor receptor and very late activation antigen 4. METHODS: Twenty-four patients with acute on chronic liver failure were randomised to receive standard therapy, standard therapy+granulocyte-colony stimulating factor (5 microg/kg/day for 6 days) and standard therapy+granulocyte-colony stimulating factor (15 microg/kg/day s.c. for 6 days). Data on CD34+cell mobilisation were compared to age-matched peripheral blood haematopoietic stem cell donors treated with granulocyte-colony stimulating factor. On day third of treatment, the expression level of CXCR4, vascular endothelial growth factor receptor and very late activation antigen 4 was analysed in mobilised CD34+ cells. RESULTS: CD34 cell count increased after the second day of granulocyte-colony stimulating factor injection in both treatment groups compared to the linear increase observed in control. After the fifth day the increase was significantly higher in healthy donors versus patients with acute on chronic liver failure. A decrease in the expression of CXCR4, very late activation antigen 4 and vascular endothelial growth factor receptor compared to premobilisation values was observed. No major side effects were observed. CONCLUSIONS: Granulocyte-colony stimulating factor treatment is able to induce CD34 mobilisation in patients with acute on chronic liver failure. The expression pattern of CXCR4, very late activation antigen 4 and vascular endothelial growth factor receptor suggests that these molecules are involved in the granulocyte-colony stimulating factor-induced stem cell mobilisation.     

肝X受体激动剂对大鼠肝脏再灌注损伤的保护作用及其机制

肝脏缺血再灌注损伤(reperfusion injury,RI)是肝脏缺血再灌注后肝脏功能障碍和结构损伤加重的现象.炎症反应是肝脏缺血再灌注损伤的重要机制之一[1].近年研究结果表明,肝X受体(live X receptor,LXR)除调节细胞内胆固醇平衡外,还可发挥抗炎效应[2].尽管LXR的抗炎作用业已明确,但其是否在RI后抑制肝脏炎症反应进而减轻损伤,目前仍鲜见报道.我们拟通过LXR化学激动剂T0901317诱导肝内LXR激活,观察其对肝脏RI后炎症反应及损伤情况的影响,研究其对肝脏RI损伤的保护机制,为治疗肝脏RI损伤提供新的作用靶点.     

G-CSF干预对老龄慢性脑缺血大鼠模型认知改善与胶质细胞可塑性的影响

目的 探讨粒细胞集落刺激因子(G-CSF)干预后,慢性脑缺血老龄鼠学习记忆功能改善与海马胶质细胞可塑性改变的相关性.方法 12月龄雄性SD大鼠2VO术后饲养3个月,构建15月龄的2VO慢性脑缺血老龄鼠模型.分为2VO/G-CSF组(n=10)、2VO/NS组(n=7),Sham组(n=10).采用Morris水迷宫检测大鼠空间学习记忆能力,通过免疫组化和图像分析技术检测海马CA1区胶质细胞的数目及胞质突起长度.结果 水迷宫实验:2VO/NS组逃逸时间显著长于Sham组和2VO/G-CSF组(P＜0.01);2VO/NS组大鼠在平台象限的停留时间少于Sham组(P＜0.01)和2VO/G-CSF组(P＜0.05);2VO/NS组大鼠跨过平台区域的次数少于Sham组和2VO/G-CSF组(P＜0.01).HE染色发现G-CSF干预后海马CA1区锥体细胞排列层数增加,胞体增大.免疫组化染色:2VO/NS组海马CA1区GFAP阳性细胞少于Sham组和2VO/G-CSF组(P＜0.05).2VO/NS组大鼠GFAP阳性细胞胞质突起长度低于Sham组和2VO/G-CSF组(P＜0.05).认知功能与胶质细胞可塑性的相关分析:2VO/NS组、Sham组及2VO/G-CSF组海马CA1区胶质细胞的数量、胞质突起长度与空间记忆能力均呈正相关(P＜0.05).结论 慢性脑缺血可致老龄鼠的空间学习记忆能力明显受损,G-CSF可诱导海马锥体细胞增生及胶质细胞可塑性改变,有效改善空间学习记忆功能.其中,胶质细胞可塑性改变与空间记忆功能改善密切相关.