MicroRNA (miRNA)is a non-coding small molecule RNA,which is involved in the occu-rrence and development of tumor as an oncogene or tumor suppressor gene. The abnormal expression of many kinds of miRNAs in hepatocellular carcinoma (HCC)can directly or indirectly act on PI3K,Akt,mTOR, IGF-1R,TGF-β and other signal molecules in mTOR signal pathway,they are crucial in the appreciation,inva-sion and metastasis of HCC cells.

目前,结肠癌的发病率位于全球肿瘤第三位、死亡率第四位,严重危害人类健康 [1].因此急需寻找有效的抗结肠癌靶向治疗方法.微小 RNA (microRNA,miRNA)被认为是肿瘤发生发展过程中关键的基因调控因子.近年来关于 miRNA 调控肿瘤的报道越来越多,现对 miRNA 在结肠癌中的分子机制综述如下.

MicroRNA-183 family,located on chromosome 7,is a highly conserved miRNA family.It has been shown that miR-183 family regulates tumor related gene transcription and post-translational processing to initiate tumorigenesis and progression.Recent studies have indicate that miR-183 acts a dual-function as oncogene or tumor suppressor gene to regulate tumor proliferation,apoptosis,invasion,metastasis and other biological behavior through targeting mRNA or regulating tumor-related signaling pathways.The study on regulatory mechanisms of miR-183 family in tumorigenesis and progression may provide a novel theoretical basis for clinical diagnosis and treatment of cancer.

目的 研究红芪多糖(HPS)对糖尿病心肌病(DCM) db/db小鼠心肌细胞凋亡相关基因Bcl-2相关X蛋白(Bax)、B细胞淋巴瘤/白血病-2(Bcl-2)和半胱氨酸天冬氨酸蛋白酶3(Caspase-3)蛋白及基因表达的影响.方法 用随机数表法将db/db小鼠分为5组:高、中、低3个剂量实验组、对照组和模型组.正常组为12只同周龄同背景db/m小鼠.高、中、低3个剂量实验组分别给予HPS 200,100,50 mg·kg-1·d-1混悬液灌胃;对照组给予670 μg·mL-1罗格列酮混悬液4 mg·kg-1灌胃;模型组给予同等剂量0.9％ NaCl 0.2 mL·d-1灌胃;正常组不干预.连续干预8周.于给药前及给药后第2,4,6,8周末,以免疫印迹法检测心肌组织Bax、Bcl-2以及Caspase-3蛋白表达.结果 经HPS干预8周后,对照组、模型组和高、中2个剂量实验组的Bax蛋白水平分别为0.61±0.04,1.04 ±0.02,0.56±0.16,0.75±0.11;这4组的Bcl-2蛋白水平分别为0.87 ±0.03,0.40±0.07,1.04±0.06,0.72±0.05;这4组的Caspase-3蛋白水平分别为0.44±0.05,0.78±0.11,0.28±0.05,0.63±0.12,模型组与正常组比较,差异均有统计学意义(均P＜0.01);高、中2个剂量实验组与模型组比较,差异均有统计学意义(均P＜0.01).结论 HPS可以增加糖尿病心肌病db/db小鼠心肌组织中Bcl-2蛋白表达、而降低Bax与Caspase-3的蛋白表达.

目的 研究红芪多糖(HPS)对db/db小鼠糖尿病心肌病的病理形态及Ⅰ、Ⅲ型胶原蛋白表达的影响.方法 用随机数表法将6周龄雄性db/db小鼠分为5组:正常组、模型组、对照组和高、中、低3个剂量实验组.模型组和正常组ab/m小鼠均给予0.9％ NaCl 10 μL·g-1灌胃;对照组给予4mg· kg-1 ·d-1罗格列酮混悬液灌胃;实验组分别给予200,100,50 mg·kg-1 ·d-1HPS混悬液灌胃,每组12只,均连续灌胃8周.Masson染色观察心肌组织病理改变,实时荧光定量核酸扩增法与蛋白质印迹法分别检测心肌组织Ⅰ、Ⅲ型胶原α与mRNA与蛋白的表达.结果 模型组、高、中2个剂量实验组和对照组的Ⅰ型胶原的mRNA分别为5.04±1.35,1.57 ±0.21,2.73 ±0.57,2.06±0.47;这4组的Ⅲ型胶原的mRNA分别为3.12 ±0.25,1.59 ±0.09,1.95 ±0.12,1.67±0.21;这4组的Ⅰ型胶原蛋白表达分别为1.29 ±0.05,0.87±0.03,0.96±0.04,0.89±0.02;这4组的Ⅲ型胶原蛋白表达分别为0.89±0.03,0.69 ±0.01,0.76±0.01,069±0.01.3个给药组与模型组比较,上述指标均明显降低,差异均有统计学意义(均P＜0.01;除了中剂量实验组的Ⅰ型胶原的mRNA为P＜0.05以外).心肌组织中Ⅰ、Ⅲ型胶原的蛋白表达与Masson染色胶原纤维阳性染色面积值呈正相关,相关系数分别为0.955,0.909(P ＜0.01).结论 HPS能抑制Ⅰ、Ⅲ型胶原的表达水平及Ⅰ/Ⅲ胶原蛋白的比值,其对糖尿病心肌病db/db小鼠的心肌保护作用可能是通过影响Ⅰ、Ⅲ型胶原的表达而发挥作用.

目前,化疗仍然是肝癌治疗的主要手段,将三氧化二砷(As2O3)应用于肝癌的治疗虽大大地提高了疗效,但是毒副作用较大.为此,本实验组将3'-叠氮-2',3'-脱氧胸腺核苷(AZT)作为As2O3的增敏剂与As2O3联合起来用于肝癌的治疗,在保证疗效的基础上有效地减少了As2O3的用量,但AZT的增敏机制未明,水通道蛋白9 (AQP9)的深入研究为明确AZT的增敏机制提供了重要线索.

Tanshinone Ⅱ A (Tan Ⅱ A) is an extract of traditional Chinese medicine Salvia miltiorrhiza,which can play a natural antioxidant effect.It is mainly used in the treatment of cardiovascular disease.Which has anti-atherosclerosis,reduced myocardial infarct size and improve myocardial oxygen consumption,inhibition of thrombosis,inhibition of platelet aggregation,antitumor activity and other effects,and are mainly used for the treatment of cardiovascular disease in clinical applications.In recent years,a large number of clinical studies and animal experiments have confirmed that tanshinone Ⅱ A in the inhibition of colon cancer cell proliferation,promote cell apoptosis,promote cell invasion and metastasis and other aspects of prominent anti-cancer effect,making it the object of concern to researchers.In this paper,tanshinone ⅡA anti-colon cancer effect of studies were reviewed.

目的 探讨As2O3(arsenic trioxide)联合丹参酮ⅡA(TanshinoneⅡA,TanⅡA)对结肠癌细胞SW620的基质金属蛋白酶-9(MMP9)、血管内皮生长因子(VEGF)、CD44v6、nm23-H1 mRNA表达的影响,研究联合用药对结肠癌肿瘤细胞的分子作用机制.方法 SW620细胞复苏,按照干预药物不同分为空白对照组、As2O3单药组、TanⅡA单药组、联合用药组、阳性对照组(5-Fu组),采用实时荧光定量PCR法检测细胞中MMP9、VEGF、CD44v6、nm23-H1 mRNA表达的变化.结果 与空白对照组相比,各用药组MMP9、VEGF、CD44v6的表达量显著降低(P<0.01),nm23-H1 mRNA的表达量明显增高(P<0.01);As2O3与TanⅡA联合用药组的MMP9、VEGF、CD44v6表达量明显低于各单药组(P<0.05),nm23-H1表达量明显上调(P<0.05).结论 As2O3协同TanⅡA抑制人结肠癌SW620细胞的作用可能是通过调控MMP9、VEGF、CD44v6及nm23-H1的表达来实现的.

Aquaporin 9 (AQP9),one of members of the cell membrane protein family,plays an important role in maintaining metabolism and water balance in vivo.AQP9 could also play an importan role in development of tumors,such as migration,metastasis and apoptosis of tumor cells.In addition,AQP9 is of great significance in judging prognosis of tumors.

Objective To explore the effect of hedysarum polybotrys polysacchcaide (HPS)on myocar-dial fibrosis of db /db mice with diabetic cardiomyopathy (DCM)by taking TGF-β1 /Smads signaling pathway as the index.Methods Altogether 60 six-week-old male db /db mice were randomly divided in-to five groups:HPS high-,mid-,low-dose group,rosiglitazone group and model group,additional 12 non transgenic db /m male mice with the same background were assigned into the normal group.The mice ex-cept for those of the normal group were intragatrically administered (i.g.)corresponding medicines for consecutive 8 weeks.Before treatment and every two weeks during the period of i.g.drugs,the body weight and blood glucose were detected.At the end of Week 8,HE staining was used to observe the&nbsp;pathological changes of left ventricular myocardial fibers,Masson staining was used to observe the degree of left ventricular myocardial collagen fibrosis,and Western blot,RT-PCR were used to measure the pro-tein and mRNA expressions of TGF-β1 and Smad2,Smad3 in cardiac muscle tissue.Results Eight weeks after treatment,the blood glucose of rats in HPS high-,mid-dose group,and rosiglitazone group decreased significantly compared with model group (P <0.05).The sections of HE staining showed that the model rats’myocardial cells structure became unclear and some of them were swollen and deformed obviously,even the nucleus disappeared.The sections of Masson staining showed that bright green colla-gen fibers were heaped up between myocardial cells and around blood vessels of the model rats.The pro-tein and mRNA expressions of TGF-β1 ,Smad2 and Smad3 had no significant difference between model group and HPS low-dose group (P >0.05),but the other groups decreased significantly compared with the model group (P <0.05),especially the HPS high-dose group or rosiglitazone group was superior to mid-dose group (P <0.05).Conclusion The effect of HPS against myocardial fibrosis in db /db mice with DCMto slow down the progression of DCMwas proved,and its potential mechanism may be related to inhibitation of TGF-β1 /Smads signaling pathway.

目前,结直肠癌是影响人类健康最常见的肿瘤之一.我国结肠癌的发病率日益增加,它是位于我国第5位、世界第3位的恶性肿瘤.虽然结直肠癌治疗的相关研究取得了一定进展,但其治疗手段仍然以手术及放化疗为主,术后的复发及转移仍是治疗的关键难题[1].因此寻找有效的结肠癌治疗途径迫在眉睫.我国古代用砷类矿物药砒霜即三氧化二砷(As2O3)治疗牛皮癣、梅毒及一些恶性肿瘤.1865年Lissaver用亚砷酸治疗慢性粒细胞白血病被认为是历史上首次使用抗癌药物治疗恶性肿瘤[2].

Objective To explore protection mechanism of Hedysari polysaccharide (HPS) on myocardial fibrosis of db/db mice with diabetic cardiomyopathy.Methods Sixty db/db mice (7-week-old) were randomly divided into five groups:high-dose experimental group,middle-dose experimental group,low-dose experimental group (HPS:200,100,50 mg · kg-1),control group(rosiglitazone:4 mg · kg-1) and model group(0.9％ NaCl,gavege);while 12 db/m mice (7-week-old) were normal group.Each group had 12 mice.Blood glucose was detected at the baseline before intervention and at end of 2,4,6 and 8 weeks after intervention separately.The activity of blood lipid,superoxide dismutase (SOD),glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA) were detected by biochemical method after 8 weeks.The degree of myocardial fibrosis was observed by masson staining.The qPCR method and Western blotting method were used to detect the expression of peroxisome proliferator-activated receptor γ (PPARγ),nuclear transcription factor 2 kappa B (NF-κB) mRNA in myocardial tissue.Results The activities of SOD(mg · mL-1)in model group,high-dose experimental group,middle-dose experimental group,control group were 140.70 ± 1.04,145.81 ± 0.99,142.21 ± 1.09,145.70 ± 1.10,respectively with statistical difference compared with the model (P ＜ 0.05).The activities of GSH-PX(U ·mg-1) in above four groups were 110.91 ±0.82,114.94-0.78,112.10 ±0.86,114.84 ±0.86 with statistical difference compared with the model(all P ＜0.01).The contents of MDA(nmol · mg-1) were 7.20 ±0.49,5.82 ±0.52,6.62 ±0.67,5.80 ±0.52 in the four groups which significantly decreased (P ＜ 0.05,P ＜ 0.01).The expression of PPARγ mRNA were 0.34 ± 0.11,0.68 ± 0.05,0.48 ±0.03,0.49 ±0.03,0.93 ± 0.05 and protein above were 0.75 ±0.12,1.78 ±0.08,1.44 ±0.07,1.07 ±0.05,1.63 ±0.02 in above five groups with statistical difference compared with the model(all P ＜0.05).NF-kappa B mRNA were 3.35 ±0.81,1.67 ±0.22,2.34 ±0.39,2.05 ±0.44 and protein were 1.17 ±0.04,0.56 ±0.12,0.86 ±0.13,0.55± 0.12 in the four groups with statistical difference compared with the model (all P ＜ 0.05).Conclusion HPS can reduce the development of myocardial fibrosis by increasing the expression of PPARγ and inhibiting the activity of NF-κB,controlling oxidative stress and inflammatory reaction through the PPARγ-NF-κB signaling pathway.

三氧化二砷(As2O3)作为一种化疗药物,在多种肿瘤的治疗中取得了一定的疗效,被广泛应用于基础研究和临床研究中.然而不良反应限制了其在临床中的应用,因此如何减少不良反应是As2O3在肿瘤治疗中的研究重点.本文就As2O3在肿瘤治疗中的不良反应机制及减少不良反应的方法 做一综述.

Objective To observe the effects of hedysari polysaccharide (HPS) on myocardial fibrosis and the expression of MMP-2/TIMP-2 in model mice of diabetic cardiomyopathy; To discuss the mechanism of action of prevention and treatment of myocardial fibrosis in diabetes.Methods Sixty mice were randomly divided into model group, rosiglitazone group and HPS high-, mediume- and low-dose groups. The normal group was 12 non-transgenic male BKS.Cg-Dock7m+/+Leprdb/JNjumice with the same age. Each group was given relevant medicine for gavage, for 8 weeks. Blood glucose of mice before and after medication 2, 4, 6, and 8 weeks was detected. The levels of MMP-2, MMP-2 and MMP-9 in myocardium were measured by Masson staining. The protein expressions of MMP-2 and TIMP-1 in myocardium were detected by Western blot.Results Compared with the model group, the blood glucose of HPS (high- and medium dose) groups and rosiglitazone group decreased significantly. Masson staining showed that the green fibers in the model group significantly increased and rosiglitazone group and HPS high-dose group decreased compared with the model group. Western blot showed that the expressions of MMP-2 in model group and MMP-2/TIMP-2 ratio were declined significantly, while the expression of MMP-2 was increased and TIMP-2 was decreased significantly, and the ratio of MMP-2/TIMP-2 increased in rosiglitazone group and HPS high- and medium-dose group.Conclusion HPS may reduce the degree of myocardial fibrosis in model mice with diabetic cardiomyopathy. The therapeutic effect of HPS may be to relieve myocardial fibrosis in model mice by increasing the ratio of MMP-2/TIMP-2.

目的:探讨As2O3(arsenic trioxide,As2O3)联合运用丹参酮ⅡA(TanshinoneⅡA,TanⅡA)对结肠癌SW620细胞迁移和侵袭的影响,并探讨联合用药与单独用药的差异.方法:应用MTT法检测不同浓度As2O3、TanⅡA及两药的联合用药对人结肠癌SW620细胞的增殖抑制作用,确定最佳联合用药浓度;分别用As2O3和TanⅡA以及两药联合处理结肠癌SW620细胞,同时以未经药物处理的SW620细胞作为空白对照,5-氟脲嘧啶(5-Fluorouracil,5-FU)处理组为阳性对照组.应用Transwell小室检测细胞迁移和侵袭能力的变化.结果:MTT试验结果表明,As2O3(2.5μg/mL)联合TanⅡA(10μg/mL)为最佳联合用药浓度.经As2O3和TanⅡA联合干预后,SW620细胞的迁移和侵袭能力比空白对照及单药组明显降低(P<0.01).结论:As2O3联合TanⅡA作用能够明显抑制人结肠癌SW620细胞的侵袭转移能力.

探讨翻转课堂结合以团队为基础学习(Team-Based Leaning,TBL)教学模式在临床血液学检验实验教学中的应用效果.研究发现,翻转课堂结合TBL教学模式有助于提高学生学习兴趣和自主学习能力,帮助学生更好地掌握知识点.

目的 研究党参水提物对衰老模型小鼠肝组织microRNA(miRNA)表达谱的影响,探究中药党参抗衰老的分子机制.方法 将100只昆明种小鼠,随机分为正常对照组,D-半乳糖致衰老模型组,低、中、高党参剂量干预组.连续造模42 d,随时监测模型小鼠的一般症状和体质量变化;并在造模结束后检测各组小鼠血清谷丙转氨酶(ALT)和碱性磷酸酶(ALP)的值变化;利用Affymetrix miRNA 4.0微阵列芯片筛选了D-半乳糖致小鼠衰老和高剂量党参干预衰老过程中差异表达的miRNA,利用生物信息学工具对芯片结果进行聚类及信号通路分析.结果 与正常对照组小鼠比较,衰老模型组小鼠血清ALT和ALP值显著升高(P＜0.05);与衰老模型组比较,党参干预组小鼠血清ALT和ALP值有下降趋势,其中高剂量干预组ALP下降较显著(P＜0.05);芯片聚类分析显示衰老模型组的miRNA表达谱与正常对照组和高剂量党参干预组明显分开,而高剂量党参干预组和正常对照组的miRNA表达谱聚在一起;D-半乳糖致衰老和党参抗衰老相关的差异表达miRNA主要都属于7个miRNA基因簇(miR-466a/b cluster、miR-297a cluster、miR-145a cluster、miR-486 cluster、miR-299a cluster、miR-127 cluster和miR-134 cluster);生物信息学分析显示致衰老过程中差异表达miRNA的靶基因功能显著富集于29条信号通路(P＜0.01),党参干预过程中差异表达miRNA的靶基因,参与调控的信号通路有67个(P＜0.01).结论 miRNA的靶向调控作用在D-半乳糖致衰老及党参抗衰老过程中发挥着重要作用.

Objective: To investigate the effects of arsenic trioxide (As2O3) combined with 3’-azido-3’-deoxythymidine (AZT) on the migration and invasion of human liver cancer HepG2 cells, and to explore its possible mechanism.Methods: The liver cancer HepG2 cells were treated with As2O3 or AZT alone or in combination; meanwhile, the HepG2 cells without any treatment were used as the blank control. The migration and invasion of HepG2 cells were measured by wound healing assay and Transwell migration and invasion assays, respectively. The expression mRNA levels of matrix metallopeptidase 2 (MMP2) and vascular endothelial growth factor (VEGF) were detected by real-time fluorescent quantitative-PCR. The protein expression levels of MMP2, VEGF, extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were detected by Western blotting.Results: The migration and invasion abilities of HepG2 cells in As2O3 combined with AZT group were significantly decreased than those in the blank control, As2O3 and AZT alone groups (all P 0.05).Conclusion: As2O3 combined with AZT has synergistic inhibitory effects on the migration and invasion abilities of HepG2 cells. The effect may be related to phosphorylation of ERK1/2 pathway and down-regulation of MMP2 and VEGF expressions. DOI:10.3781/j.issn.1000-7431.2015.11.230

在传统灸法的基础上,将艾绒进行特殊加工,并配以强身保健的中药,如人参、附子、干姜、苍术等制成无烟灸条,对实验性小鼠的神阙穴施灸,观察其对机体免疫功能的影响.实验结果表明,此法能明显提高小鼠吞噬细胞的吞噬率和红细胞C3b受体花环形成转换率.与空白对照组和有烟灸对照组比较,有显著性差异.且对小鼠的肺及支气管无大的影响,未引起肺及支气管静脉充血,与有烟灸对照组比较,有显著性差异.