高浓度游离脂肪酸对胰岛细胞凋亡及相关基因表达的影响

目的：观察高浓度游离脂肪酸体外对胰岛细胞凋亡和凋亡相关基因表达的影响。方法：应用TUNEL法检测高浓度游离脂肪酸培养后大鼠胰岛细胞和小鼠βTc3细胞凋亡百分率，应用定量RT～PCR(QRT—PCR)检测培养后bc1-2、bax、c—myc、p53和fas mRNA的表达。结果：高浓度游离脂肪酸使原代培养的大鼠胰岛细胞和βTc3的凋亡细胞比例明显增加。胰岛细胞凋亡过程中，诱导凋亡基因bax、c—myc、fas的tuRNA表达水平明显升高，抵抗凋亡基因bcl-2mRNA表达水平明显下降，p53 mRNA表达水平无明显改变。结论：游离脂肪酸可能通过诱导胰岛细胞凋亡导致或加重糖尿病，其中bc1-2／bax mRNA表达比率变化可能起重要作用。     

伏利诺他联合顺铂对A549细胞的抑制作用及其机制研究

目的本文旨在研究伏利诺他(SAHA)与顺铂(DDP)联用对A549细胞在体外和体内的抑制作用,并初步探索其作用机制。方法在体外实验中,采用MTT法检测SAHA和DDP对A549细胞增殖的影响;Tunel法检测SAHA和DDP对细胞凋亡的影响。在体内实验中,建立肿瘤动物模型,将小鼠随机分为模型组、DDP组和DDP+SAHA组。每组小鼠给予相应剂量药物。4周后,所有小鼠处死并取肿瘤组织,采用RT-PCR和Western blot法检测bcl-2、bax和p53的mRNA及蛋白的表达水平。结果MTT实验结果提示DDP+SAHA抑制细胞增殖的作用比DDP强。Tunel实验结果提示DDP+SAHA处理后的A549细胞凋亡数目比DDP单独处理的多(P <0.05)。在体内实验中,DDP+SAHA组小鼠肿瘤体积明显小于模型组和DDP组(P <0.05)。RT-PCR和Western blot实验结果提示,DDP+SAHA可增加bax和p53的mRNA及蛋白表达水平,同时降低bcl-2 mRNA和蛋白表达水平。结论 SAHA与DDP联合应用对A549细胞和肿瘤模型小鼠具有较强的抗肿瘤作用,其作用可能是通过对bcl-2/bax和p53的调控来实现的。     

HIF-1α反义寡核苷酸对肝癌细胞增殖凋亡的影响及机制

目的：本研究通过应用 HIF-1α反义寡核苷酸（antisense oligodeoxynucleotide,ASODN）处理 SMMC-7721肝癌细胞,观察其对 SMMC-7721肝癌细胞增殖的作用和对细胞周期及凋亡率的影响及其机制。方法肝癌细胞系SMMC-7721分对照组和试验组。对照组细胞常规培养,试验组细胞施加 HIF-1α的 ASODN 干预,设浓度梯度和时间梯度。检测不同药物浓度、不同时间对 SMMC-7721细胞的增殖的作用及对细胞周期和凋亡率的影响。对 bcl-2、bax、surviving mRNA 表达产物相对定量,并对 SMMC-7721细胞胞浆 bcl-2、bax、survivin 蛋白进行相对定量分析。结果与对照组相比,各处理组 OD 值均有显著下降,细胞数量降低,且各实验组相比呈明显的时间-剂量依赖效应,差异有统计学意义（ P <0.05）。不同浓度 HIF-1α的 ASODN 处理细胞后,均可使各处理组 G0/ G1期细胞增多,S 期细胞减少,且呈时间-剂量依赖效应,差异有统计学意义（ P <0.05）。不同浓度 HIF-1α的 ASODN 处理细胞不同时间后,与对照组相比,各实验组 bcl-2 mRNA 和 survivin mRNA 表达均有显著下降,差异有统计学意义（ P <0.05）。而 bax 的 mRNA无明显变化趋势（ P >0.05）。不同浓度 HIF-1α的 ASODN 处理细胞不同时间后,与对照组相比,各实验组 bcl-2和survivin 的蛋白表达显著下降,bax 的蛋白表达显著增加,差异有统计学意义（ P <0.05）。结论 HIF-1α的 ASODN可以将 SMMC-7721肝癌细胞株阻滞于 G0/ G1期,影响细胞周期进程,抑制细胞增殖,促进细胞凋亡。HIF-1α促进增殖抑制凋亡的可能机制是上调肝癌细胞 Survivin 和 bcl-2的表达,下调 bax 的表达。针对 HIF-1α抑制剂的应用为肝癌的治疗提供了新思路。     

紫杉醇对肝癌SMMC7721细胞凋亡的诱导作用及对相关基因表达的影响

目的：探讨紫杉醇对肝癌SMMC7721细胞凋亡的诱导作用及对bcl-2和bax基因的影响。方法：用浓度为5ug·ml-1的紫杉醇处理肝癌SMMC7721细胞后,利用DNA琼脂糖凝胶电泳,TUNEL法检测其细胞凋亡;通过原位杂交法、免疫组化法,测定紫杉醇诱导肝癌SMMC7721细胞产生凋亡时,凋亡抑制基因bcl-2和凋亡促进基因bax的mRNA和蛋白表达。结果：紫杉醇作用一定时间后,SMMC7721细胞产生凋亡、bcl-2显著下降、bax表达显著增高。结论：紫杉醇通过调节细胞凋亡抑制基因bcl-2和细胞凋亡促进基因bax的作用,从而诱导肝癌SMMC7721细胞产生凋亡。     

番茄红素对宫颈癌HeLa细胞bax、bcl-2基因表达的影响

目的 研究番茄红素对人宫颈癌HeLa细胞的诱导凋亡作用并探讨其对凋亡相关基因bax和bcl-2表达的影响。方法不同浓度番茄红素分别处理HeLa细胞24～72h后，MTT法检测细胞的生长活性，RT-PCR方法检测凋亡相关基因bax，bcl-2的表达。结果实验结果随着番茄红素浓度的增加，bax基因mRNA表达增加而bcl-2的mRNA表达减少。结论番茄红素对HeLa细胞的生长具有抑制作用，可促进宫颈癌HeLa细胞发生凋亡，bcl-2基因的减少与bax基因表达增加可能是HeLa细胞凋亡的机制之一。     

聚维酮联合多柔比星灌注对膀胱癌组织中Fas和Caspase-3 mRNA表达的影响

目的探讨聚维酮（PVP）联合多柔比星膀胱灌注对膀胱肿瘤组织中凋亡相关蛋白Fas、Caspase-3mRNA表达的影响。方法选取术前24h膀胱灌注生理盐水30mL加多柔比星20mg（对照组）,10％PVP30mL加20mg多柔比星（实验组）,术后病理证实为浅表性膀胱肿瘤标本各25例。采用RT-PCR方法检测肿瘤组织中凋亡相关蛋白Fas、Caspase-3mRNA的表达水平。结果FasmRNA和Caspase-3 mRNA在对照组中的阳性率较实验组高,且差异存在高度统计学意义（P〈0．01）。结论PVP联合多柔比星膀胱灌注能上调凋亡相关蛋白Fas、Caspase-3mRNA的表达。     

重组人白介素-18对辐射损伤小鼠细胞周期素基因及凋亡相关基因表达的调节作用

为探讨重组人白介素-18（IL-18）对辐射损伤小鼠骨髓细胞周期素基因（cyclinD1）及凋亡相关基因（bel-2和bax）mRNA表达的作用，对32只小鼠分4组进行辐射损伤，第14天用原位杂交法检测小鼠骨髓单个核细胞cyclinD1、bel-2和bax mRNA的表达。结果表明，与对照组相比，重组人IL-18组骨髓细胞促凋亡基因bax mRNA表达显著减少（P〈0．01），而cyclinD1和bcl-2 mRNA的表达显著增强（P〈0．01）。结论：重组人IL-18抗辐射损伤可能是通过上调细胞周期素基因cychnD1和bcl-2的表达及降低bax mRNA的表达，促进造血细胞的增生和提高机体免疫力，从而达到保护机体的目的。     

消瘤1号通过影响bax和bcl-2的表达诱导人乳腺癌细胞MCF-7凋亡

目的：探讨中成药消瘤1号诱导MCF-7人乳腺癌细胞凋亡的作用及其分子机制。方法：采用细胞培养技术,用不同浓度的含药血清（含药物浓度为1、10、100、1 000μg/ml）处理MCF-7细胞,用MTT法检测药物对细胞增殖的影响;以流式细胞仪测定碘化丙啶染色细胞细胞周期的变化;采用实时-PCR法检测bax mRNA和bcl-2 mRNA表达。结果：消瘤1号处理MCF-7细胞后,随着药物浓度增加,作用时间延长,细胞增殖速度减慢。流式细胞仪检测结果显示,消瘤1号使MCF-7细胞阻滞于S期,随着药物浓度的增加,细胞凋亡逐渐增加。消瘤1号还能够促进细胞中bax mRNA表达,减少bcl-2 mRNA表达,并呈浓度依赖性。结论：消瘤1号诱导MCF-7细胞凋亡,其机制涉及bax/bcl-2比值升高,引起线粒体释放细胞色素C。消瘤1号有可能开发为治疗乳腺癌的药物。     

山奈酚诱导人小细胞肺癌H446细胞凋亡及机制

目的探讨山奈酚对人小细胞肺癌H446细胞的抑制作用,并研究其作用机制。方法采用MTT法、DAPI染色、流式细胞术等方法检测山奈酚对H446细胞增殖及凋亡的影响;使用Western blot检测山奈酚处理后H446细胞中p53、bax和bcl-2的表达变化。结果山奈酚抑制人小细胞肺癌H446细胞增殖,促进H446细胞阻滞于S期及G2/M期,诱导该细胞株凋亡,上调p53、bax的表达水平,降低bcl-2的表达水平。结论山奈酚对H446细胞有明显的抑制作用,该抑制作用与山奈酚诱导的细胞周期阻滞和细胞凋亡有关。     

AKT体内外抗肝癌作用及机理的初步研究

目的：观察AKT对人肝癌细胞SMMC-7721及小鼠H22肝癌移植性肿瘤的抑制作用，并探讨以紫草总色素为主要成分，制备而成的AKT的抗肿瘤作用机制。方法：用MTT法分析AKT对人肝癌细胞SMMC-7721的增殖抑制作用绘制作用生长曲线；建立小鼠H22肝癌移植性实体瘤模型，通过绘制瘤块生长曲线及计算肿瘤抑制百分率评价体内抑瘤效果，流式细胞术检测不同剂量AKT作用SMMC-7721细胞48h后细胞凋亡率及细胞周期变化，并检测Bax及Bcl-2蛋白的表达情况；RT-PCR检测AKT作用SMMC-7721细胞24h后，bcl-2 mRNA及baxmRNA的表达情况。结果：（1）MTT提示AKT对SMMC-7721细胞具有显著抑制作用；（2）体内实验表明，AKT对小鼠H22肝癌移植性肿瘤有一定的抑制作用。（3）Giemsa染色后在光镜下可见AKT给药组多数细胞出现形态改变，胞体变小，胞质浓缩拉长，呈拉丝状，核质比增大，核膜完整，核固缩，染色质不均一或边集，胞浆内较多空泡的典型凋亡特征；Hoechst 33258染色后细胞核出现细胞核固缩，出现凋亡小体等明显的凋亡形态学变化；流式细胞术检测显示AKT作用SMMC-7721细胞后，中、高剂量组均检测到明显亚G1凋亡峰；给药组S期细胞明显降低，G2／M期细胞明显增多，细胞周期阻滞于G2／M期；药物处理后Bcl-2及Bax的表达均下调，且Bcl-2／Bax值降低；RT-PCR检测结果显示给药组bcl-2 mRNA及bax mRNA表达水平均出现下调，bcl-2／bax比值降低；体内实验瘤组织免疫组化结果显示给药组Bcl-2表达下调，Bax及Caspase-3表达均出现上调。结论：AKT对人肝癌SMMC-7721细胞具有明显体外抗增殖作用，对小鼠移植性肿瘤H22也呈现了明显的抑制作用。其效应机制可能与阻滞细胞周期于G2／M期，下调bcl-2 mRNA及Bcl-2蛋白表达，上调Caspase-3表达，从而诱导肿瘤细胞凋亡，抑制肿瘤细胞增殖有关。     

维生素K3体外降低Ehrlich腹水癌细胞对阿霉素的抗药性

AIM: To study the effect of menadione (Men) reducing doxorubicin (Dox) resistance in Ehrlich ascites carcinoma (EAC) cells resistant to Dox (EAC/Dox cells). METHODS: Glutathione (GSH) content and membrane fluidity were measured by fluorometric assay and fluorescence depolarization assay, respectively. Glutathione S-transferase (GST) activity was measured with 1-chloro-2,4-dinitrobenzene as the substrate. Cell viability was determined by 3-(4, 5-dimethylthiazol)-2, 5-diphenyltetrazolium bromide assay. RESULTS: GSH content, GST activity, and membrane fluidity in EAC/Dox cells were higher than those in EAC cells (P < 0.01). The IC50 (95% confidence limits) for Dox on EAC/Dox cell was 22.3 (15.8-28.8) mg.L-1. Relative resistance of Dox in EAC/Dox cells was 42-fold. Pretreatment of EAC/Dox cells with Men 5 or 10 mg.L-1 decreased intracellular GSH content (P < 0.01). Men 1 mg.L-1 had no obvious effect on GSH content in EAC/Dox cells (P > 0.05), but decreased the elevated membrane fluidity efficiently (P < 0.05). Men had no obvious effect on GST activity in EAC/Dox cells (P > 0.05). IC50 of Dox was reduced to 9.6 (7.8-11.3), 6.0 (2.8-9.2), or 5.3 (3.9-6.7) mg.L-1 in EAC/Dox cells pretreated with Men 1, 5, or 10 mg.L-1. CONCLUSION: Men reduced Dox resistance effectively due in part to its depletion of GSH content in EAC/Dox cells.     

粉防己碱和蝙蝠葛碱减低抗三尖杉酯碱的人白血病HL60细胞对阿霉素的抗性(英文)

目的:研究粉防己碱(Tet)和蝙蝠葛碱(Dau)能否减低抗三尖杉酯碱(Har)的人早幼粒白血病HL60抗性株对阿霉素(Dox)的抗性。方法:细胞计数法和克隆形成法测定药物毒性,流式细胞光度术分析细胞周期变化,荧光法测定Dox含量。结果:无细胞毒性的Tet和Dau明显地增强Dox对HL60抗性细胞的生长抑制作用,使克隆形成率从Dox单药的60％分别降低到0.2％,9.2％,使阻断在G_2M期的抗性细胞增多,但Tet和Dau不增强Dox对敏感的HL60细胞的毒性。Tet使胞内Dox积聚增加。结论:Tet和Dau减低抗Har的HL60细胞对Dox的抗性,其机制是增加Dox在细胞内积聚。     

吗丙嗪和阿霉素合用对肿瘤细胞周期及DNA合成的影响

目的：观察吗丙嗪（Ｐｒｏ）和阿霉素（Ｄｏｘ）合用对肿瘤细胞周期及ＤＮＡ合成的影响，以探讨吗丙嗪增强阿霉素抗肿瘤作用之机制。方法：采用拒染法观察Ｐｒｏ，Ｄｏｘ和Ｐｒｏ＋Ｄｏｘ对小鼠体外艾氏腹水癌细胞（ＥＡＣ）的杀伤作用；采用标记前体物参入法和显微分光光度术观察两药合用对ＥＡＣ细胞周期及ＤＮＡ合成的影响。结果：Ｐｒｏ２１．４６，４２．９２和６４．３８μｍｏｌ·Ｌ－１增强Ｄｏｘ对ＥＡＣ细胞的杀伤作用；Ｐｒｏ（２１４．５９μｍｏｌ·Ｌ－１）和Ｄｏｘ（１８．０２μｍｏｌ·Ｌ－１）合用对ＥＡＣ细胞ＤＮＡ合成有明显的抑制作用；用药后４～８ｈＧ１期细胞增加，ＤＮＡ直方图左移，各用药组细胞分裂指数无明显差异。结论：Ｐｒｏ可增强Ｄｏｘ的抗肿瘤作用，其机理可能与Ｐｒｏ加强Ｄｏｘ对ＤＮＡ合成的抑制及对Ｇ１期细胞累积作用增强有关。     

一种新番荔枝内酯单体atemoyacin—B克服肿瘤多药抗药性

目的 探讨ａｔｅｍｏｙａｃｉｎ－Ｂ（Ａｔｅ）克服肿瘤多药抗药性（ＭＤＲ）作用及机制。方法 Ｂｕｌｌａｔａｃｉｎ（Ｂｕｌ）为阳性对照物,细胞毒测定以ＭＴＴ法,Ｐｇｐ功能测定以Ｆｕｒａ２－ＡＭ法,细胞内药物积累测定以荧光分光光度计法;细胞凋亡测定以流式细胞仪法,结果：Ａｔｅ对ＭＣＦ－７／Ｄｏｘ,ＭＣＦ－７,ＫＢＶ２００和ＫＢ细胞的ＩＣ５０分别为１２２,１２０,１．３４,１．２７ｍｍｏｌ．Ｌ＾－１,Ａｔ     

三种双苄基异喹啉生物碱调节多药耐药性的作用及与维拉帕米的比较

目的：比较轮环藤碱（Ｃｙｃ）、海岛轮环藤碱（Ｉｎｓｒ）和海岛轮环藤酚碱（Ｉｎｓｎ）与维拉帕米（Ｖｅｒ）体外调节多药耐药性（ＭＤＲ）的作用。方法：细胞毒试验采用ＭＴＴ法，细胞内阿霉素（Ｄｏｘ）积累采用荧光分光光度法测定。结果：Ｃｙｃ，Ｉｎｓｒ，Ｉｎｓｎ和Ｖｅｒ在分光光度法测定。结果：Ｃｙｃ，Ｉｎｓｒ，Ｉｎｓｎ和Ｖｅｒ在ＭＤＲ细胞系ＭＣＦ－７／Ａｄｒ和ＫＢｖ２００能显著调节Ｄｏｘ和长春新碱的耐药性具有     

2—ASG —3—（3‘,5’—双吗啉甲基—4‘—羟基）—苯甲酰吲哚（HWL—12）逆转肿…

AIM: To explore the reversal of multidrug resistance (MDR) by indole derivative HWL-12. METHODS: Cytotoxicity was determined by tetrazolium (MTT) assay. The function of P-gp was examined by Fura 2-AM assay. Cellular accumulation of doxorubicin (Dox) was measured by fluorescence spectrophotometry. RESULTS: HWL-12 10 mumol.L-1 markedly increased Fura-2 accumulation and was 17.2-fold reversal of MDR in MCF-7/ADR cells. The cellular Dox accumulation in MDR cells was increased in the presence of HWL-12 on the MCF-7/ADR cells. No effect was observed for Dox accumulation in the presence of high Ca2+ (addition of CaCl2) or low Ca2+ (addition of egtazic acid). CONCLUSION: HWL-12 has a potent MDR reversal action which was associated with the increase of cellular Dox accumulation in MDR cells and not related with calcium ion concentration.     

The anti-hepatitis drug DDB chemosensitizes multidrug resistant cancer cells <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis> by inhibiting P-gp and enhancing apoptosis

Summary Purpose: DDB (dimethyl-4,4′-dimethoxy-5,6,5′6′-dimethylene dioxybiphenyl-2,2′-dicarboxylate) is a synthetic hepatoprotectant which has been widely used to treat chronic viral hepatitis B patients in China for more than 20 years. In this study, we evaluated DDB as a multidrug resistance (MDR) chemosensitizing agent. Methods: A panel of sensitive and resistant cancer cell lines were treated with various concentration of DDB, and the effect on chemosensitivity and accumulation of anticancer drugs; promotion of apoptosis and P-glycoprotein (P-gp) expression were determined by MTT (Dimethyl thiazolyl-2,5-diphenyltetrazolium bromide) assay, fluorospectrometry and flow cytometry respectively. Drug resistance reversal activity of DDB was also examined in BALB/c nude mice bearing both acquired MDR human nasopharyngeal carcinoma KBv200 and parental KB xenografts. The effect of DDB on the pharmacokinetics of Dox and hematological toxicity induced by Dox was measured in ICR and C₅₇/BL mice, respectively. Results: DDB at nontoxic concentrations of 12.5, 25 and 50 μM partly reversed the resistance to vincristine, doxorubicin, paclitaxel in acquired MDR breast carcinoma MCF-7/Adr cells, KBv200 and intrinsic MDR human hepatocarcinoma Bel₇₄₀₂ cells, whereas no chemosensitizing effect of DDB was observed in sensitive KB and MCF-7 cells. DDB increased the intracellular accumulation of doxorubicin and inhibited surface P-gp expression in MCF-7/Adr cells. Furthermore, it was found that DDB promoted doxorubicin-induced apoptosis of Bel₇₄₀₂ cells through enhanced caspase-3 activation. Co-administration of DDB at 300 and 500 mg/kg orally to nude mice increased the antitumor activity of vincristine to KBv200 xenografts without a significant increase in toxicity. In contrast, Co-administration of DDB did not inhibit the growth of KB xenografts. DDB also markedly reduced the decrease of leukocytes in doxorubicin-treated C₅₇/BL mice. Co-administration of DDB increased Dox concentration in ICR mice bearing S180 sarcoma, but no pharmacokinetical interaction with Dox was observed. Conclusion: These results indicate that DDB has MDR reversal activity by inhibiting P-gp and when used in combination with anti-cancer drugs, it could potentially be used as a clinical treatment for P-gp-mediated MDR cancers.     

Activity of Doxorubicin Covalently Bound to a Novel Human Serum Albumin Microcapsule

Doxorubicin is widely used in the treatment of human malignancies, however is associated with significant cardiac, bone marrow and gastro-intestinal toxicity. Delivery systems may ameliorate this toxicity and increase treatment specificity by increasing the proportion of drug delivered to sites of disease. We have developed a novel preparation of doxorubicin (Dox) covalently linked to a heat stabilised human serum albumin microparticle (HSAM) carrier (median particle diameter of 4 m) and assessed its activity in 4 malignant cell lines.Materials and methods. Doxorubicin microcapsules were compared with free doxorubicin in the rat carcinoma cell line, WRC256, and the human lines, OVCAR3, MCF7 and the Dox resistant MCF7/Dox, using a cell counting technique. IC50 were calculated from regression analysis of the resulting survival curves. Endocytosis of the microcapsules by cells in culture was observed. The rate of microcapsule uptake was assessed using dual wavelength filtered fluorescence microscopy and flow cytometry.Results. The mean IC50 following incubation with the Dox microcapsules was around 5 times greater than Dox for WRC256 (p < 0.001), MCF7 (p < 0.01) and for OVCAR3 (p < 0.01). MCF7/Dox was significantly more sensitive to Dox microcapsules than free Dox (p = 0.034). A negative correlation between the rate of microcapsule uptake and the IC50 values for each cell line in culture exists (r = –0.96, p = 0.04).Conclusions. We conclude that: 1) Doxorubicin microcapsules retain activity in vitro and appear to overcome p-glycoprotein mediated Dox resistance. 2) The observed activity of Dox microcapsules correlates with the rate of particle uptake. Further studies in animal tumour models are in progress.     

Doxorubicin-loaded nanospheres bypass tumor cell multidrug resistance.

We have demonstrated that in vitro resistance of tumor cells to doxorubicin (Dox) can be fully circumvented by using doxorubicin-loaded nanospheres (Dox-NS), consisting of biodegradable polyisohexylcyanoacrylate polymers of 300 nm diameter and containing 2.83 mg of Dox per 31.5 mg of polymer. Five different multidrug-resistant cell lines, characterized by mdr1 amplification, were used in this study: Dox-R-MCF7, a human breast adenocarcinoma; SKVBL1, a human ovarian adenocarcinoma; K562-R, a human erythroleukemia; and two murine lines: P388-Adr-R, a monocytic leukemia of DBA2 mouse, and LR73MDR, a Chinese hamster ovarian cell line. These lines were 38.7, 210, 232, 143 and 20 times more resistant than their corresponding sensitive counterparts, respectively. Using Dox-NS, we obtained complete reversion of drug resistance in vitro, i.e. cell growth inhibition comparable with that obtained with sensitive cells exposed to free Dox. In vivo, we significantly prolonged the survival of DBA2 mice which had previously received P388-Adr-R cells by i.p. injections of Dox-NS, while free Dox injection was ineffective toward this rapidly growing tumor. (Prolongation of survival time: 115% vs 167% after Dox vs Dox-NS treatment, respectively.) Using the MCF7 cell line and its resistant variant, we studied the intracellular concentration and the cytoplasmic and nuclear distribution of Dox by laser microspectrofluorometry (LMSF). In sensitive cells, we observed a similar accumulation and distribution of Dox whatever the form of Dox delivery, i.e. whether free or carried by nanospheres. Analysis by LMSF showed that 99% of intranuclear Dox was bound to DNA after treatment with both forms of Dox. Of Dox, 81 and 83% were found in the intranuclear compartment of sensitive cells incubated with free Dox and Dox-NS, respectively. Resistant cells incubated with Dox-NS accumulated the same amount of Dox as sensitive cells incubated with free Dox or with Dox-NS. Dox, when loaded in nanospheres, bypasses the efflux mechanism responsible for multidrug resistance. LMSF analysis showed that Dox, transported and released by nanospheres, interacts with DNA identically in sensitive and resistant cells.     

卡维地洛、比索洛尔和多沙唑嗪降压疗效比较

目的：观察并比较卡维地洛（Car）、比索洛尔（Bis）和多沙唑嗪（Dox）治疗轻、中度原发性高血压的降压疗效和安全性。方法：选择48例原发性高血压患者,随机分成3组。Car组15例（Car25-50mg,po,qd）;Bis组16例（Bis5-10mg,po,qd）;Dox组17例（Dox4mg,po,qd）。3组疗程均为4wk。检测各组服药后的血压、心率、肝肾功能、血糖和血电解质等。结果：Car组的降压总有效率为80.0％,Bis组为81.25％,Dox组为70.59％,3组疗效无显著差别（P＞0.05）,Car与Dox对心率无影响,而Bis具有减慢心率作用。3种药物对肝肾功能、血糖和血电解质无明显影响。结论：Car、Bis和Dox疗效相似,均能有效降低轻、中度原发性高血压,且无明显不良反应。