Osthole prevents cognitive impairment through modulating neuron cells in Aβ_(25-35)-injected mice

OBJECTIVE To investigate the effects of osthole on learning and memory impairment of AD mice induced by injection of Aβ25-35 and the content of Ca2+, GLU and Aβ1-42 in the brain tissue and peripheral blood. METHODS Mice were randomly assigned to sham operation, Aβ25-35, Aβ25-35+Ost-L,Aβ25-35+Ost-M, and Aβ25-35+Ost-H group. Water maze test was performed to assessing spatial learning ability of mice. It is determined that the MDA level and the activity of SOD in the brain tissue of mice in each group by colorimetry. The GLU kit and Ca2 +kit were used to detect the GLU, Ca2 +in tissue and serum. ELISA was used to detect the expression of Aβ1-42 in the hippocampus and serum of mice. HE staining and silver staining were used to detect neuron apoptosis and pathological changes in brain slices and so on. RESULTS(1) Effects of osthole on learning and memory: With the increase of training day,the escape latencies continuously reduced in each experimental group, the escape latencies of the model group was longer on the 1 st, 2 nd, 3 rd, and 5 thdays than the normal group, the difference was statistically significant(day 3 and 4: P<0.05, day 5: P<0.01); compared with the model group, the escaping latency on the 5 thday of the OST low-medium high-dose group was significantly shortened, which was statistically significant(P<0.05).(2) Effects on oxidative stresspathway: the SOD activity of AD mice in the hippocampus model group was lower than that in the normal group, which was statistically significant(P<0.05); The SOD activity in the OST group was higher than that in the model group, which was statistically significant(P<0.05). The MDA content in the model group was significantly higher than that in the normal group(P<0.05). The MDA content in the OST high-dose group was lower than that in the model group, which was statistically significant(P<0.05).(3) Effects of GLU levels on neurotransmitters:the results of the detection of GLU in cortical area and GLU in serum of AD mice in OST dose groups showed that serum GLU levels in the model group were significantly lower than those in the sham group, which was statistically significant(P<0.05). GLU levels in the cortical area were also significantly higher than those in the sham group, which was statistically significant(P<0.05). Compared with the model group, GLU levels in the OST administration group were significantly down-regulated. Among the serum, the effect of medium dose group was obvious. Although there was a trend of down-regulation in the cortical administration group, there was no statistical significance.(4) Changes in Ca2+concentration in the brain. Detection of intracellular Ca2 +concentration in AD mice by OST doses showed that,compared with the sham group, the model group was significantly upregulated in cortical Ca2 +levels.There was no statistical difference in the administration group. Compared with the model group, the concentration of Ca2+in the OST-H group significantly decreased.(5) Effect on levels of Aβ1-42 in hippocampus and serum: model group had significantly higher Aβ1-42 levels in hippocampus than in sham operation group, which was statistically significant(P<0.05). Aβ1-42 in serum was also significantly upregulated compared to the sham group, which was statistically significant(P<0.05). Compared with the model group, the levels of Aβ1-42 in the OST administration group were significantly down-regulated,with the lower and middle doses in the hippocampus being more significant, while the serum was more pronounced at lower doses.(6) Silver staining to detect the tangles of hippocampal neurons: Neuron tangles in the hippocampal CA1 region showed a dark brown-yellow granule distribution in the nuclei of the model group(positive expression). Nerve cell body and dendrites, axons are black or black red,background light yellow. Compared with the model group, the administration group has improved significantly. CONCLUSION OST improves spatial learning and memory of dementia model mice injected with Aβ25-35 in both hippocampus. Experimental studies have shown that OST has different degrees of regulation on neuronal apoptosis, Ca2 +/GLU/oxidative stress and other pathways, and it plays a role in improving multiple AD pathological changes and delaying the pathogenesis of neurodegenerative diseases.     

怡心健脑颗粒对D-半乳糖合β-AP25-35诱导AD小鼠的药效研究

目的观察怡心健脑颗粒对老年痴呆症（AD）小鼠学习记忆及抗氧化能力的影响。方法运用D-半乳糖合β-AP25-35诱导小鼠AD模型,水迷宫法观察怡心健脑颗粒对AD小鼠学习记忆成绩的影响,并测定小鼠血清、肝脏与脑组织中丙二醛（MDA）、超氧化歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、谷胱甘肽（GSH）的含量。结果与对照组比较,模型组AD小鼠的学习记忆成绩明显下降,其血清、肝脏及脑组织中MDA含量明显升高,SOD、GSH、GSH-Px含量明显下降;与模型组比较给药组AD小鼠的学习记忆成绩明显提高,血清、肝脏及脑组织中SOD、GSH、GSH-Px含量明显升高,MDA含量降低。结论怡心健脑颗粒对D-半乳糖合β-AP25-35诱导的AD小鼠具有健脑益智药理作用,并能提高其抗氧化能力。     

染料木素对小鼠抗氧化作用的研究

目的：研究染料木素对小鼠抗氧化作用的影响。方法：将80只小鼠随机均分为对照组、染料木素低剂量组、染料木素中剂量组和染料木素高剂量组,观察不同剂量组的染料木素对小鼠心肌组织、脑组织和肝组织中SOD活性和MDA含量的影响。结果：染料木素低剂量组、中剂量组和高剂量组均能提高小鼠心肌组织、脑组织和肝组织中SOD活性,降低心肌组织、脑组织和肝组织中MDA含量;与对照组两两比较,其差异有统计学意义（P〈0.05）,其剂量呈现依赖性。结论：染料木素对小鼠具有良好的抗氧化作用,能够明显提高小鼠心肌组织、脑组织和肝组织中SOD活性,降低MDA含量。     

原花青素对 D半乳糖联合 AlCl3诱导的阿尔茨海默病大鼠海马 Aβ、tau和SOD的影响

目的：研究原花青素对D-半乳糖（D-gal）联合三氯化铝（AlCl3）诱导的阿尔茨海默病大鼠海马Aβ、tau和超氧化物歧化酶（SOD）的影响。方法：D-gal腹腔注射（i.p.）180 mg · kg^-1 · d^-1联合AlCl3灌胃（i.g.）15 mg · kg^-1 · d^-112周建立阿尔茨海默病模型。将造模成功大鼠随机分为模型组、维生素E组、原花青素低剂量组、原花青素高剂量组,另设空白对照组。造模后每日灌胃给相应药物一次,连续8周。于末次给药后处死,取大鼠海马部位脑组织,采用Western blot检测Aβ、SOD、tau蛋白表达。结果：与空白对照组相比,模型组Aβ、tau蛋白表达显著增加,SOD蛋白表达显著减少,差异有统计学意义（P〈0.01）。与模型组相比,随着原花青素剂量的增加,大鼠Aβ、tau蛋白表达减少,SOD蛋白表达增加,差异有统计学意义（P〈0.01,P〈0.05）。结论：原花青素可改善D-gal联合AlCl3诱导的AD大鼠海马病变,其机制可能与提高海马SOD活性有关。     

Phytoceramide ameliorates ß-amyloid protein-induced memory impairment and neuronal death in mice

The present study was performed to investigate the protective effect of phytoceramide against ß-amyloid protein (Aβ) (25–35)-induced memory impairment and its underlying mechanisms in mice. Memory impairment in mice was induced by intracerebroventricular injection of 15 nmol Aβ (25–35) and measured by the passive avoidance test and Morris water maze test. Chronic administration of phytoceramide (10, 25 and 50 mg/kg, p.o.) resulted in significantly less Aβ (25–35)-induced memory loss and hippocampal neuronal death in treated mice compared to controls. The decrease of glutathione level and increase of lipid peroxidation in brain tissue following injection of Aβ (25–35) was reduced by phytoceramide. Alteration of apoptosis-related proteins, increase of inflammatory factors, and phosphorylation of mitogen activated proteins kinases (MAPKs) in Aβ (25–35)-administered mice hippocampus were inhibited by phytoceramide. Phosphatidylinositol 3′-kinase (PI3K)/Akt pathway and phosphorylation of cyclic AMP response element-binding protein (CREB) were suppressed, while phosphorylation of tau (p-tau) was increased in Aß (25–35)-treated mice brain; these effects were significantly inhibited by administration of phytoceramide. These results suggest that phytoceramide has a possible therapeutic role in managing cognitive impairment associated with Alzheimer’s disease. The underlying mechanism might involve inhibition of p-tau formation via anti-apoptosis and anti-inflammation activity and promotion of PI3K/Akt/CREB signaling process.     

槐白皮对放射损伤人鼠骨髓VEGF、G-CSF的表达及超微结构的影响

目的:通过检测急性放射损伤小鼠骨髓组织中血管内皮细胞生长因子(VEGF)、粒细胞集落刺激因子(G-CSF)的表达及骨髓细胞超微结构的变化,探讨槐白皮对骨髓造血细胞和造血微环境的影响.方法:实验随机分为5组,即正常、照射对照和槐白皮高、中、低剂量(0.8、0.4、0.2mL·kg-1)组.采用免疫细胞化学SABC染色法检...     

荔枝核皂苷对老年痴呆大鼠的干预作用研究

目的:建立老年痴呆(Alzheimer’s disease,AD)大鼠模型,探讨荔枝核皂苷对AD大鼠的治疗作用及其机制。方法:50只SD大鼠分为:对照组、模型对照组和低、中、高剂量荔枝核皂苷治疗组,共5组,每组10只;Morris水迷宫实验检测各组大鼠的逃避潜伏时间和平台跨越次数;Western blot实验检测各组脑组织β淀粉样蛋白(β-amyloid protein,Aβ)的表达变化;流式细胞仪检测各组脑组织活性氧(ROS)表达的改变。结果:AD大鼠模型组与对照组比较,逃避潜伏时间出现显著性地延长(P<0.01),平台跨越次数显著性地减少(P<0.01)。荔枝核皂苷治疗后AD大鼠的逃避潜伏时间和平台跨越次数得到显著性地改善(P<0.05)。AD大鼠脑组织Aβ的表达水平显著高于正常对照组,高、中、低剂量荔枝核皂苷治疗组可以剂量依赖性地降低模型鼠脑组织中Aβ的表达水平。对照组、模型对照组、低剂量荔枝核皂苷治疗组、中剂量荔枝核皂苷治疗组、高剂量荔枝核皂苷治疗组ROS表达水平的相对值分别为6.12±0.61、9.54±1.42、8.33±1.26、7.68±1.14、7.23±0.73,模型组显著高于对照组(P<0.01),荔枝核皂苷治疗可以显著降低模型组脑组织中ROS的表达水平(P<0.05)。结论:荔枝核皂苷具有抗AD大鼠痴呆的活性,减少AD大鼠脑组织Aβ和ROS的生成是其主要的作用机制。     

淀粉样β蛋白片段25~35下调大鼠海马PI3K/Akt/p70S6K信号传导通路(英文)

目的探讨阿尔茨海默病(AD)的淀粉样β蛋白(Aβ)的沉积是否损害神经细胞存活的信号传导通路。方法实验分为生理盐水对照组;Aβ25-35组;Aβ25-35+布洛芬组;Aβ25-35+布洛芬+LY294002组;Aβ25-35+LY294002组。大鼠分别灌胃给予布洛芬7.5或15 mg.kg-1,每日1次,连续3周后,左侧脑室内注射Aβ25-35(10 μL, 1 mmol.L-1),之后继续灌胃给予布洛芬1周。PI3K特异性阻断剂LY294002 (5 μL, 4 mmol.L-1)在注射Aβ25 -35前1 h左侧脑室内注射。注射Aβ25-35后1周,取海马CA1区,Western免疫印迹法观察P53,Bax, FasL, Bcl-2, Akt和p70S6K的蛋白表达水平。应用半胱氨酸天冬氨酸蛋白酶(caspase)3活性测定试剂盒分析caspase 3活性变化,RT-PCR方法观察p70s6k mRNA表达水平。结果脑室内注射Aβ25-35可引起大鼠海马CA1区磷酸化Akt/PKB和磷酸化p70S6K表达明显降低,分别从对照组1.32±0.14和0.769±0.028下降到0.69±0.08和0.479±0.032。同时,海马CA1区促凋亡蛋白P53, Bax和FasL表达及caspase 3活性明显增加,抗凋亡蛋白Bcl-2表达明显降低。预先注射LY294002可使caspase 3活性较单独注射Aβ25-35组进一步增加。给Aβ25-35前后连续给予布洛芬4周可明显对抗Aβ25-35引起的上述变化。LY294002可明显减弱布洛芬上调磷酸化Akt/PKB和磷酸化p70S6K表达的作用。结论 Aβ25-35引起抗凋亡通路PI3K/Akt/p70S6K下调可能参与AD的神经元损伤。布洛芬具有较好的对抗作用,这可能与上调PI3K/Akt/p70S6K通路中的一些蛋白有关。     

黄芩素对肝癌H22荷瘤小鼠的抑瘤作用研究

目的:研究黄芩素对肝癌H22荷瘤小鼠的抑瘤作用。方法:以H22肝癌细胞接种于正常小鼠左前肢腋窝皮下复制肝癌H22荷瘤模型。实验分为模型对照、环磷酰胺(30mg·kg-1)和黄芩素高、中、低剂量(80、40、20mg·kg-1)组。灌胃给药,每天1次,连续15d。末次给药后处死小鼠,剥离完整的肿瘤组织称重,并计算肿瘤抑制率;流式细胞仪分析细胞周期分布和凋亡率;按试剂盒说明书测定肿瘤组织中半胱氨酸蛋白酶(Caspase)-3的活性;RT-PCR测定瘤组织中B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-2相关X蛋白(Bax)的mRNA表达水平。结果:高、中剂量黄芩素可显著抑制模型小鼠体内肿瘤生长(P<0.01或P<0.05),抑制率分别为61.63%和44.65%;可显著提高G0/G1期细胞百分比(P<0.05),并减少S期细胞(P<0.01或P<0.05)。与模型对照组比较,黄芩素高、中、低剂量组细胞凋亡率显著提高(P<0.01或P<0.05)。高、中剂量黄芩素可显著增强肿瘤组织中Capcase-3活性(P<0.01或P<0.05),抑制Bcl-2mRNA表达(P<0.01或P<0.05);高剂量黄芩素可显著提高肿瘤组织中BaxmRNA表达(P<0.05)。结论:黄芩素可促进肝癌H22荷瘤小鼠肿瘤细胞的凋亡,其机制可能与增强Capcase-3活性、提高Bax表达,并抑制Bcl-2表达有关。     

BDE-153对胰岛素抵抗和脂肪因子的影响及机制初探

目的 研究2,2',4,4',5,5'-六溴联苯醚(2,2',4,4',5,5'-Hexabromodiphenyl ether,BDE-153)对C57BL/6小鼠胰岛素抵抗和脂肪因子的影响,并初步探讨其可能的机制.方法 雄性C57BL/6小鼠随机分为对照组、BDE-153染毒高、中和低剂量组.利用腹腔注射葡萄糖耐量...     

健脾和胃方对大鼠肝微粒体CYP3A1酶活性的影响

目的研究健脾和胃方对大鼠肝微粒体细胞色素P450同工酶3A1（CYP3A1）活性的作用。方法 25只大鼠随机分为5组：空白对照组（生理盐水1 mL·kg-1·d-1,14 d）、地塞米松组（100 mg·kg-1·d-1,3 d）和健脾和胃方高、中、低剂量组（7.146,3.573,1.786 mg·kg-1·d-1,14 d）,每组5只,灌胃给予相应的药物。采用高效液相色谱-紫外检测法,以睾酮为探针,测定睾酮经大鼠肝微粒体温孵后转化的代谢产物6β-羟基睾酮（6β-OHT）的生成速率,以评价各组CYP3A1酶活性。结果空白对照组、地塞米松组和健脾和胃方高、中、低剂量组6β-OHT的生成速率分别为（7.29±0.66）、（27.46±2.35）、（3.51±0.48）、（4.90±1.18）、（6.52±1.23）nmol·mg-1·min-1,健脾和胃方高、中、低剂量组6β-OHT的生成速率与地塞米松组均有显著性差异（P〈0.05）。高、中剂量组与空白对照组有显著性差异（P〈0.05）,低剂量组与空白对照组无显著性差异（P〉0.05）。结论本实验结果表明健脾和胃方对大鼠肝药酶CYP3A1酶活性无诱导作用,健脾和胃方的高、中剂量组能使大鼠肝药酶CYP3A1酶活性下降。     

葛根芩连煎剂与颗粒剂的抗腹泻、抑菌药效研究

目的:比较葛根芩连汤与颗粒剂的抗腹泻、抑菌药效。方法:抗腹泻实验中将小鼠分为9组,即空白(等容生理盐水)、模型(等容生理盐水)、葛根芩连微丸(1g.kg-1)、葛根芩连煎剂高、中、低剂量(2、1、0.5g.kg-1)和葛根芩连颗粒高、中、低剂量(0.54、0.27、0.135g.kg-1)组。灌胃给药,每天1次,连续3d,末次给药30min后灌胃蓖麻油10mL.kg-1,测定小鼠稀便率。肠推进机能实验中将小鼠分为8组,即空白(等容生理盐水)、葛根芩连微丸(1g.kg-1)、葛根芩连煎剂高、中、低剂量(2、1、0.5g.kg-1)和葛根芩连颗粒高、中、低剂量(0.54、0.27、0.135g.kg-1)组。灌胃给药,每天1次,连续2d,末次给药20min后灌胃碳末,测定小鼠肠推进率。体外抑菌试验中测定葛根芩连煎剂与颗粒剂对5种菌的最低抑菌浓度。结果:与模型组比较,葛根芩连煎剂高、中剂量组与葛根芩连颗粒高、中、低剂量组稀便率显著减少(P<0.01);与空白组比较,葛根芩连煎剂高、中、低剂量与葛根芩连颗粒高、中、低剂量组小鼠肠推进率无显著改变(P>0.05)。葛根芩连颗粒对4种菌的最低抑菌浓度均低于葛根芩连煎剂。结论:葛根芩连颗粒比葛根芩连煎剂抗腹泻、抑菌作用更佳。     

愈疡胶囊对细菌感染皮炎模型大鼠的抗炎作用及对TLR/NF-κB通路的影响

目的:研究愈疡胶囊对细菌感染皮炎模型大鼠的抗炎作用及对Toll样受体/核因子κB(TLR/NF-κB)通路的影响.方法:采用肉汤稀释法测定愈疡胶囊对金黄色葡萄球菌的最低抑菌浓度(MIC)和最低杀菌浓度(MBC).将50只大鼠随机分为模型组、阳性对照组(阿莫西林克拉维酸钾,以阿莫西林计120 mg/kg)和愈疡胶囊高、中...     

大黄酚脂质体对阿尔采末病模型小鼠学习记忆的改善作用

目的研究大黄酚脂质体对β-淀粉样肽(Aβ25-35)致阿尔采末病(Alzheimer’s disease,AD)模型小鼠学习记忆障碍的影响,及脑组织超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性的变化。方法小鼠1次性脑室内注射凝聚态Aβ25-353μl(1.0 mmol.L-1)制造AD小鼠模型,然后尾静脉注射相应药物或溶剂,采用Y型迷宫法和跳台法测试大黄酚脂质体对小鼠学习记忆的影响,采用比色法测定小鼠脑组织SOD和CAT活性。结果脑室1次性注射3μl Aβ25-35溶液可引起小鼠学习记忆障碍,同时使脑组织SOD和CAT活性降低;而大黄酚脂质体制剂可不同程度改善Aβ25-35造成的学习记忆障碍,提高脑组织SOD和CAT活性,延长小鼠断头耐缺氧的生存时间。结论大黄酚脂质体制剂对Aβ25-35致AD小鼠记忆障碍有保护作用,其作用机制可能与增强抗氧化酶CAT和SOD活性,提高脑组织对氧自由基的清除能力有关。大黄酚脂质体有望成为治疗AD疾病临床应用的新剂型。     

益智仁挥发油抗帕金森模型小鼠黑质神经元凋亡的作用研究

目的:研究益智仁挥发油对帕金森(PD)模型小鼠黑质致密部尼氏小体、酪氨酸羟化酶(TH)表达的影响和神经元凋亡的对抗作用。方法:实验分为6组,即正常对照(等容生理盐水)、模型(等容生理盐水,ig生理盐水第6天起同时复制模型,连续7d,每天1次)、司来吉兰(10mg·kg-1,ig司来吉兰第4天起同时复制模型,连续7d,每天1次)和益智仁挥发油高、中、低剂量(2.5、0.833、0.278mL·kg-1,ig益智仁挥发油第6天起同时复制模型,连续7d,每天1次)组。ip1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)复制C57BL小鼠PD模型。采用尼氏染色法观察尼氏小体表达;SABC免疫组化染色法观察益智仁挥发油对TH表达的影响;TUNEL染色法检测黑质神经元凋亡。结果:与正常对照组比较,模型组小鼠黑质神经元的尼氏小体、TH表达阳性细胞数明显减少,神经元凋亡显著增加;与模型组比较,益智仁挥发油高、中剂量组小鼠黑质神经元内尼氏小体显著增多;益知仁挥发油高、中、低剂量组TH表达阳性细胞数显著增多,而凋亡细胞数量显著减少。结论:益智仁挥发油能对抗PD模型小鼠黑质神经元细胞凋亡。     

丙二酸次氮酰胺对刀豆蛋白刺激的胶原性关节炎模型大鼠CD4~+CD25~+调节性T淋巴细胞体外分化的影响

目的:研究来氟米特活性代谢物丙二酸次氮酰胺(A771726)对刀豆蛋白(ConA)刺激的胶原性关节炎(CIA)模型大鼠CD4+CD25+调节性T淋巴细胞(CD4+CD25+Tregs)体外分化的影响及其治疗类风湿性关节炎的作用机制。方法:取大鼠分为正常对照组和CIA模型组,建模后制备脾淋巴细胞悬液,再分为正常组、模型组和A771726低、中、高剂量(0.1、1、10μmol·L-1)组,各组加入ConA刺激和相应药物培养液培养48h后,以MTT法检测各组脾淋巴细胞增殖情况,流式细胞术检测各组CD4+CD25+Tregs占CD4+T淋巴细胞的比例;反转录-聚合酶链式反应检测各组CD4+CD25+Tregs特异性标志物Foxp3和转化生长因子β(TGF-β)mRNA表达情况;酶联免疫吸附测定法检测各组TGF-β浓度。结果:与正常组比较,模型组脾淋巴细胞增殖明显升高(P<0.01),CD4+CD25+Tregs占CD4+T淋巴细胞的比例、Foxp3和TGF-βmRNA表达、TGF-β浓度均明显降低(P<0.05);与模型组比较,A7717263个剂量组脾淋巴细胞增殖明显降低(P<0.05或P<0.01),A771726高剂量组CD4+CD25+Tregs占CD4+T淋巴细胞的比例明显升高,A771726中、高剂量组Foxp3和TGF-βmRNA表达、TGF-β浓度均明显升高(P<0.05或P<0.01)。结论:A771726可抑制CIA模型大鼠脾淋巴细胞增殖,诱导CD4+CD25+Tregs的分化,其机制可能与上调TGF-β的表达和分泌有关。     

SUD-35/羟丙基-β-环糊精包合物的制备及其小鼠体内药效学初步研究

目的:制备苯甲酰脲类微管微丝抑制剂SUD-35/羟丙基-β-环糊精包合物(SUD-35/HP-β-CD),以提高SUD-35的水溶性和稳定性,并对其小鼠体内药效学进行初步考察。方法:采用饱和水溶液法,以SUD-35/HP-β-CD投药比(A)、包合温度(B)、包合时间(C)、搅拌速度(D)为考察因素,以包合率为考察指标,设计正交试验筛选最佳制备工艺并进行验证试验和溶解度测定;以差示扫描量热(DSC)法及X射线衍射(XRD)法验证包合物;对肝癌H22细胞实体瘤模型小鼠腹腔注射包合物低、中、高剂量(以SUD-35计)每日1次,共7d,计算末次给药后24h的抑瘤率,并与环磷酰胺比较。结果:最佳制备工艺为A:1∶5,B:50℃,C:60min,D:100r·min-1;以此工艺所制3批包合物的平均包合率约为75.8%;SUD-35原料及其包合物在水中的溶解度分别为0.00032、0.65g·L-1;DSC和XRD法证实包合物形成;低、中、高剂量抑瘤率分别为(38.25±0.57)%、(63.45±1.20)%、(69.26±1.15)%,环磷酰胺组为(71.52±1.16)%。结论:SUD-35/HP-β-CD包合物的制备工艺简便、易行,可极大地提高SUD-35的水溶性,其高剂量对肝癌H22细胞在小鼠体内的生长具有与环磷酰胺相似的抑制作用。     

重组去整合素rAdinbitor对肝癌细胞H22生长的抑制作用

目的:探讨源于白眉蝮蛇的重组去整合素rAdinbitor对肝癌细胞H22生长的抑制作用及其机制。方法:通过诱导重组表达、纯化、鉴定等步骤获得rAdinbitor;采用右腋皮下注射1×106个H22细胞制备肝癌小鼠模型,随机分为模型组(0.9%氯化钠注射液0.2 ml/kg)、阳性对照组(重组人血管内皮抑制素1.65 mg/kg)和高、中、低剂量治疗组(rAdinbitor 5、1.25、0.5 mg/kg),每组8只,肌肉注射相应药物,每日1次,连续给药3周后处死小鼠,取瘤称质量,镜下观察肿瘤组织切片中5个视野下的血管数量。结果:成功诱导表达并纯化rAdinbitor,其蛋白含量为1.4 mg/ml,相对分子质量约为9 kD。各组小鼠瘤质量和血管数量分别为模型组:(1.513±0.922)g和3.34±0.58;阳性对照组:(0.562±0.304)g和1.33±0.58;高剂量治疗组:(0.318±0.205)g和1.18±0.56;中剂量治疗组:(0.434±0.323)g和1.32±0.60;低剂量治疗组:(0.536±0.328)g和1.35±0.58。与模型组比较,各剂量治疗组小鼠的瘤质量和血管数量均明显下降(P<0.05);与阳性对照组比较,中、高剂量治疗组小鼠的瘤质量差异有统计学意义(P<0.05),高剂量治疗组小鼠的血管数量差异有统计学意义(P<0.05),其余差异无统计学意义。结论:rAdinbitor对H22细胞的生长具有明显的抑制作用,其机制可能是抑制瘤组织周边新血管的形成。     

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。     

鸡血藤醇提物对血虚模型小鼠的补血作用

目的:研究鸡血藤醇提物对血虚模型小鼠的补血作用。方法:通过放血以复制小鼠失血性血虚模型;通过腹腔注射环磷酰胺(25 mg/kg)以复制小鼠化学性血虚模型;通过皮下注射乙酰苯肼(20 mg/kg)同时控制饮食以复制小鼠综合血虚模型。60只KM种小鼠随机分为正常对照(等体积生理盐水)组、模型(等体积生理盐水)组、乌鸡白凤丸(4 g/kg)组与鸡血藤醇提物高、中、低剂量(30、15、7.5 g/kg)组。制备模型的同时灌胃给药,每天1次,连续10 d。测定小鼠红细胞计数(RBC)、血红蛋白(HGB)、红细胞压积(HCT)、血小板计数(PLT)。结果:与正常对照组比较,模型组小鼠RBC、HGB、HCT、PLT降低,差异具有统计学意义(P<0.01)。与模型组比较,鸡血藤醇提物高、中、低剂量组小鼠RBC、HGB升高,差异具有统计学意义(P<0.01或P<0.05);鸡血藤醇提物高、中剂量组小鼠HCT、PLT升高,差异具有统计学意义(P<0.01或P<0.05)。结论:鸡血藤醇提物对血虚模型小鼠有良好的补血作用,其机制可能与调节血液系统有关。