较长时间肠外营养支持病人加用生长激素的临床观察

目的观察重组人生长激素(rHGH)对较长时间接受肠外营养(PN)支持患者的影响.方法16例患者接受传统肠外营养2周后,加用rHGH(8～12IU/d)2周.观察患者应用rHGH前后尿氮排出量和体重的变化.结果患者在加用rHGH2周后较单纯接受传统肠外营养时体重有所增加(50.2±4.2kgvs52.3±4.3kg,P=0.01);尿氮排出量在联合应用rHGH3天后明显减少(P=0.026).重要脏器功能未见明显变化.结论提示肠外营养支持联合应用rHGH可以增加患者体重,减少尿素氮排出量.

胃癌组织bcl-2基因表达与细胞凋亡和增生的关系

目的:探讨胃癌细胞bcl-2基因表达水平与肿瘤细胞增生活性及细胞凋亡程度的关系.方法:胃癌组织53例,用原位杂交及免疫组化染色法分别检测bcl-2 mRNA,bcl-2蛋白和增生细胞核抗原(PCNA)的表达,并采用凋亡细胞原位检测方法对组织切片中的凋亡细胞进行观察和比较.结果:胃癌组织表达bcl-2 mRNA 41例(77.4%),表达Bcl-2蛋白43例(81.1%),X2检验表明两种方法检测阳性率差异无显著性.胃癌53例增生期细胞标记物PCNA表达及凋亡细胞的阳性率均为100%,细胞凋亡和细胞增生指数呈显著性负相关(r=-0.993,P＜0.01).随胃癌细胞Bcl-2蛋白表达水平升高,PCNA阳性细胞指数相应增加,肿瘤凋亡细胞指数则相应减少,Bcl-2蛋白+++组与++组间(t=2.552,2.699,P＜0.05)及前两组分别与-组和+组间(t=4.487,3.975,2.807,3.094,4.885,5.816,3.404,3.895,P＜0.01)凋亡和增生细胞指数差异均有显著性.结论:胃癌细胞bcl-2基因高表达可引起细胞凋亡减少与过度增生.

Calmodulin (CaM), widely distributed in almost all eukaryotic cells, is a major intracellular calcium receptor responsible for mediating the Ca2 + signal to a multitude of different enzyme systems and is thought to play a vital role in the regulation of cell proliferative cycle[1，2]. Recently, many studies showed that CaM is also present in extracellular fluid such as cell culture media and normal body fluid and has been reported to stimulate proliferation in a range of normal and neoplastic cells, apparently acting as an autocrine growth factor[3-11]. In 1988, Crocker et al reported for the first time that addition of extracellular pure pig brain CaM could promote DNA synthesis and cell [7]proliferation in K562 human leukaemic lymphocytes[7].After that, more and more research was done on extracellular CaM and evidences demonstrated that extracellular CaM could also stimulate cell proliferation in normal human umbilical vein endothelial cells[5], keratinocytes[4], suspension-cultured cells of Angelica Dahurica, etc[6]. CaM is a monomeric protein of 148 amino acids that contains four homologous Ca2 + -binding domains. CaM has been highly conserved throughout the evolution. Only 1 out of 148 amino acids of human CaM is different from that of fish CaM. Complementary DNAs encoding rat, eel, chicken, human, and trypanosome CaM have been cloned.

AIM To reveal the inhibitory effects of Curcuma aromatica oil ( CAO ) on cell proliferation of hepatoma in mice.METHODS Two tumor inhibitory experiments of CAO on hepatoma in mice were conducted.The inhibitory effects of CAO on proliferation of hepatoma in mice were evaluated by DNA image cytometry and immunohistochemical staining of proliferating cell nuclear antigen (PCNA).RESULTS The tumor inhibitory rates of CAO were 52% and 51% in two experiments,respectively. Compared with those of the salinetreated control groups, both differences were statistically significant (P ＜ 0.01). In the group of mice treated with CAO, the cellular nuclear DNA OD value (249 ± 70), areas (623μnm2 ±228 μm2) and DNA (2.38 ± 0.67) index of hepatic carcinomas were significantly lower than those of the control group (430 ± 160, 1073μm2 ± 101 um2 and 4.48 ± 0.71 ). CAO also could increase diploidy cell rates (29.00% ± 9.34% vs 2.97% ± 5.69%, P＜0.01 ) and decrease pentaploidy cell exceeding rate (30.04% ± 15.10% vs 70.89%±14.94%, P＜0.01). In the group of mice treated with CAO, the labeling indexes of proliferating cell nuclear antigen (PCNA-LI) were 30% ± 4%, which were significantly lower than 40% ± 6% of the control group (P＜0.01).CONCLUSION The inhibition of CAO on the growth of hepatoma in mice might be associated with its depression on cellular proliferative activity.

胰腺癌组织STAT3的表达及其与细胞增殖和凋亡的相关性研究

STAT3是信号传导和转录激活因子(signal transducer and activator of transcription,STAT)家族的成员之一,在肿瘤的发生发展过程中起重要的作用.本研究用免疫组化方法检测胰腺癌组织中PSTAT3和其调控基因Bcl-xL的蛋白表达情况,分析胰腺癌组织中PSTAT3与胰腺癌临床病理特征及凋亡、增殖的关系,从而探讨STAT3这一细胞信号传导通路中的关键环节在胰腺癌发生发展过程中的重要作用.

Application of single and combination therapy of clarithromycin and tamoxifen to suppress breast cancer cell proliferation and metabolism

Objective This study compares the anti-tumor effects of single and combination use of clarithromycin and tamoxifen on estrogen receptor (ER) positive breast cancer cell lines,BT-483 and MCF-7 as well as triple negative cell line,MBA-MD-231,which acts as a negative control.The effect of solid breast tumor inhibition by clarithromycin is also studied.Method BT-483,MCF-7 and MBA-MD-231 were cultured in 6-well plates in a 37 ℃ humidified incubator without CO2 for 24 h prior to the addition of the test drugs.The test groups were clarithromycin ( Group 1 ),tamoxifen ( Group 2 ),clarithromycin and tamoxffen ( Group 3 ),and control ( Group 4 ).Group 3 was prepared in 1 to 1 ratio at a concentration of 1.5 mmol/L clarithromycin and 25 μmol/L tamoxifen.On the other hand,1 mm3 solid breast tumors were submerged into various groups as above for 24 h.On the harvest day,the proliferation of cancer cells and solid breast tumor samples were measured by WST-1 proliferation reagent while ATP bioluminescence assay was employed to measure the metabolic rate of the three cell lines.Results The proliferation of BT-483 and MCF-7 was suppressed most by combination use of clarithromycin and tamoxifen with statistical significance.The two drugs did not have an inhibitory effect on the hormonal negative cancer cells.For solid breast tumor samples,all the test groups showed reduced metabolic rate as compared with the control group ( P＜0.05 ).Conclusion Combination use of tamoxifen and clarithromycin are effective in suppressing cell proliferation and metabolism rate of breast cancer cells while single use of clarithromycin effectively inhibits the proliferation of solid breast tumor.

Astrocytes are specialized and most numerous glial cell type in the central nervous system and play important roles in physiology. Astrocytes are also critically involved in many neural disor-ders including focal ischemic stroke, a leading cause of brain injury and human death. One of the prominent pathological features of focal ischemic stroke is reactive astrogliosis and glial scar for-mation associated with morphological changes and proliferation. This review paper discusses the recent advances in spatial and temporal dynamics of morphology and proliferation of reactive astrocytes after ischemic stroke based on results from experimental animal studies. As reactive astrocytes exhibit stem cell-like properties, knowledge of dynamics of reactive astrocytes and glial scar formation will provide important insights for astrocyte-based cell therapy in stroke.

Long-term administration of scopolamine, a muscarinic receptor antagonist, can inhibit the survival of newly generated cells, but its effect on the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus remain poorly understood. In this study, we used immunohistochemistry and western blot methods to weekly detect the biological behaviors of nerve cells in the hippocampal dentate gyrus of adult mice that received intraperito-neal administration of scopolamine for 4 weeks. Expression of neuronal nuclear antigen (NeuN;a neuronal marker) and Fluoro-Jade B (a marker for the localization of neuronal degeneration) was also detected. After scopolamine treatment, mouse hippocampal neurons did not die, and Ki-67 (a marker for proliferating cells)-immunoreactive cells were reduced in number and reac hed the lowest level at 4 weeks. Doublecortin (DCX; a marker for newly generated neurons)-im-munoreactive cells were gradually shortened in length and reduced in number with time. After scopolamine treatment for 4 weeks, nearly all of the 5-bromo-2′-deoxyuridine (BrdU)-labeled newly generated cells were located in the subgranular zone of the dentate gyrus, but they did not migrate into the granule cell layer. Few mature BrdU/NeuN double-labeled cells were seen in the subgranular zone of the dentate gyrus. These ifndings suggest that long-term administration of scopolamine interferes with the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus, but it does not induce cell death.

Previous studies have demonstrated that doublecortin-positive immature neurons exist pre-dominantly in the superficial layer of the cerebral cortex of adult mammals such as guinea pigs, and these neurons exhibit very weak properties of self-proliferation during adulthood under physiological conditions. To verify whether environmental enrichment has an impact on the proliferation and maturation of these immature neurons in the prefrontal cortex of adult guinea pigs, healthy adult guinea pigs were subjected to short-term environmental enrichment. Animals were allowed to play with various cognitive and physical stimulating objects over a period of 2 weeks, twice per day, for 60 minutes each. Immunolfuorescence staining results indicated that the number of doublecortin-positive cells in layer II of the prefrontal cortex was signiifcantly increased after short-term environmental enrichment exposure. In addition, these doublecortin-positive cells co-expressed 5-bromo-2-deoxyuridine (a marker of cell prolifera-tion), c-Fos (a marker of cell viability) and NeuN (a marker of mature neurons). Experimental ifndings showed that short-term environmental enrichment can induce proliferation, activation and maturation of doublecortin-positive cells in layer II of the prefrontal cortex of adult guinea pigs.

Traumatic brain injury (TBI) is the leading cause of death and disability of persons under 45 years old in the United States, affecting over 1.5 million individuals each year. It had been th ought that recovery from such injuries is severely limited due to the inability of the adult bra in to replace damaged neurons. However, recent studies indicate that the mature mammalian central nervous system (CNS) has the potential to replenish damaged neurons by proliferation and neuronal differentiation of adult neural stem/progenitor cells residing in the neurogenic regions in the brain. Furthermore, increasing evidence indicates that these endogenous stem/progenitor cells may play regenerative and reparative roles in response to CNS injuries or diseases. In support of this notion, heightened levels of cell proliferation and neurogenesis have been ob-served in response to brain trauma or insults suggesting that the brain has the inherent potential to restore populations of damaged or destroyed neurons. This review will discuss the potential functions of adult neurogenesis and recent development of strategies aiming at harnessing this neurogenic capacity in order to repopulate and repair the injured brain.

Oenanthe javanica is an aquatic perennial herb that belongs to theOenanthe genus in Apiaceae family, and it displays well-known medicinal properties such as protective effects against glu-tamate-induced neurotoxicity. However, few studies regarding effects ofOenanthe javanica on neurogenesis in the brain have been reported. In this study, we examined the effects of a normal diet and a diet containing ethanol extract ofOenanthe javanica on cell proliferation and neu-roblast differentiation in the subgranular zone of the hippocampal dentate gyrus of adolescent rats using Ki-67 (an endogenous marker for cell proliferation) and doublecortin (a marker for neuroblast). Our results showed thatOenanthe javanica extract signiifcantly increased the number of Ki-67-immunoreactive cells and doublecortin-immunoreactive neuroblasts in the subgranular zone of the dentate gyrus in the adolescent rats. In addition, the immunoreactivity of brain-derived neurotrophic factor was signiifcantly increased in the dentate gyrus of theOe-nanthe javanica extract-treated group compared with the control group. However, we did not ifnd that vascular endothelial growth factor expression was increased in theOenanthe javanica extract-treated group compared with the control group. These results indicate thatOenanthe javanica extract improves cell proliferation and neuroblast differentiation by increasing brain-de-rived neurotrophic factor immunoreactivity in the rat dentate gyrus.

黄酮、异黄酮药物抑制肿瘤细胞增殖作用的新进展

目的黄酮和异黄酮是具有多种药理功能的药物,从抑制肿瘤细胞恶性增殖的角度阐明其药理作用.方法总结新文献,对黄酮和异黄酮的药物机制加以综述.结果黄酮和异黄酮具有抑制蛋白酪氨酸激酶、抑制拓扑异构酶、抑制CDK(cyclin depend kinase)、SERM(selective estrogen receptor mediator)等作用.结论黄酮和异黄酮可以作用于上述多个靶点抑制肿瘤细胞恶性增生.

周围神经损伤后远端效应器的变化

INTRODUCTIONThe peripheral nerve injury can result in loss of neural function and the rehabilitation after injuries is the problem remained to be solved in medicine. The studies of nerve injury should begin with the study of the local depressed site. Then the neuron, axon and effective apparatus should be studied[1, 2]. The function of the nerve mainly depend on the distal effective apparatus, so it is more important to study it. Recently the scholars home and abroad pay more attention to form and dynamics of the cell proliferation of the distal effective apparatus such as motor endplate, sensory corpuscle and muscle. The review about this research is as follows.

间歇性机械拉伸对体外培养兔关节软骨细胞微管蛋白-β取向的影响

目的 探讨间歇性机械拉伸对兔关节软骨细胞生长和细胞形态及骨架的影响,为软骨细胞内力学信号传导研究的提供参考.方法 采用FX-4000TM柔性基底拉伸系统对体外单层原代培养的兔软骨细胞实施正弦波、0.5 Hz、0～5%间歇性周期应变加载,每日拉伸3h,共加载3天.对照组静态培养.3天后检测细胞活力、基质合成情况以及微管蛋白-β细胞免疫荧光染色,并对细胞周期进行检测.结果 加载组软骨细胞生长良好,氨基多聚糖和蛋白多糖的合成与对照组无明显差异;但细胞增殖指数显著增高(P＜0.05);微管蛋白-β沿细胞长轴发生重排,细胞形态和取向趋于一致.结论 间歇性机械拉伸对细胞生长起到积极的作用,并且通过微管蛋白-β的重排影响细胞形态和取向.

Effect of naphthalene acetic acid on proliferation and apoptosis of mice hepatocytes

ObjectiveTo investigate the effect of naphthalene acetic acid (NAA) on proliferation and apoptosis of mice hepatocytes.MethodsFifty mice were randomly divided into five groups: positive control, normal control, low, middle and high dose of NAA groups.Mice in low, middle and high dose of naphthalene acetic acid groups were fed with 200 mg/kg, 1 000 mg/kg and 5 000 mg/kg NAA animal food, respectively.Mice in positive control, normal control groups were fed with usual animal food.After 4 weeks, mice were sacrificed and liver was separated.Three days before scarification, mice in positive control group were given 20 mg/kg ascyclophosphami daily by intraperitoneal injection.The proliferative activity of hepatocytes was detected by MTT assay.The expressions of PCNA protein and Caspase-3 were measured by immunohistochemistry method.ResultsThe proliferative activities of mice hepatocytes in high dose group and normal control group were 0.794±0.019 and 1.055±0.019, respectively.The expressions of PCNA protein and Caspase-3 in high dose group were 11.2% and 37.9%, and those in the normal group were 33.1% and 6.3%, respectively.All differences were significant (P＜0.01).ConclusionHigh dose of NAA acid could significantly inhibit proliferation and increase apoptosis of hepatocytes in mice.

含辛伐他汀药物血清对兔血管平滑肌细胞增殖的直接作用及意义

研究表明,他汀类药物在抗动脉粥样硬化(Atherosclerosis,AS)中存在许多非调脂机制[1].但目前尚存在一些问题阻碍正式认定他汀类药物通过直接作用于血管壁的抗AS作用[2].本研究采用改进血清药理学方法观察辛伐他汀对体外血管平滑肌细胞增生的影响,探讨辛伐他汀对血管平滑肌细胞的直接作用及意义.

内皮素-内皮素受体在凝血酶促进血管平滑肌细胞增殖中的作用

凝血酶是一种丝氨酸蛋白酶,催化裂解纤维蛋白原形成纤维蛋白,参与凝血过程;通过其特异性受体(凝血酶受体)激活血小板,是已知体内强的血小板聚集剂.凝血酶还是体内重要的有丝分裂原,与内皮素(ET)、血管紧张素(AT)一样作用于G蛋白偶联的受体,促进血管平滑肌增殖,与冠状动脉硬化的发生、发展和PTCA后的再狭窄有关[1].