依托咪酯乳剂用于全麻诱导的临床观察

目的：观察依托咪酯乳剂在全麻诱导中对血流动力学的影响。方法：全麻时使用静脉注射依托咪酯乳剂0.2mg/kg～0.3mg/kg诱导，观察记录患者血流动力学变化。结果：使用依托咪酯乳剂前后患者血流动力学无明显变化。结论：依托咪酯乳荆可安全用于全麻诱导。     

右美托咪啶联合依托咪酯麻醉对胃癌术后疼痛的影响

目的探讨右美托咪啶联合依托咪酯麻醉对胃癌根治术患者术后疼痛的影响。方法选取2012年1月至2014年12月间行择期胃癌根治术患者144例,按照随机数字表法分为治疗组和对照组,每组72例。治疗组患者在麻醉诱导中辅助应用右美托咪啶联合依托咪酯,对照组患者在麻醉诱导中辅助应用依托咪酯。观察两组患者入手术室时、用药时和拔管时的心率、收缩压和舒张压变化情况,观察麻醉效果及疼痛评分。结果两组患者不同时间点的收缩压和舒张压差异均无统计学意义(均P>0.05),治疗组患者用药时与拔管时的心率较对照组明显改善(均P<0.05)。两组患者的恢复自主呼吸时间和拔除气管导管时间差异均无统计学意义(均P>0.05)。治疗组患者术后疼痛评分和术后疼痛发生率均低于对照组(均P<0.05)。结论对于胃癌根治术患者,右美托咪定联合依托咪酯能保持围手术期心率稳定,减轻术后疼痛。     

不同剂量右美托咪啶复合依托咪酯对胃癌根治术后患者疼痛及感染的影响

目的 比较不同剂量右美托咪啶复合依托咪酯对胃癌根治术患者临床疗效及术后疼痛及感染的影响.方法 选取行胃癌根治术的患者78例作为研究对象,采用随机数字表法分为A、B、C3组.A组给予依托咪酯麻醉,B组给予低剂量右美托咪啶复合依托咪酯麻醉,C组给予高剂量右美托咪啶复合依托咪酯麻醉.比较3组患者血流动力学、麻醉情况、术后疼痛与感染以及不良反应发生率.结果 不同时间点,A组患者血流动力学指标变化幅度明显较B、C组大(P＜0.05).3组患者在自主呼吸恢复时间、呼之睁眼时间和拔管时间等麻醉情况方面比较均无统计学差异(P＞0.05).A组患者疼痛患者及感染以及不良反应发生率远远高于B组及C组,差异有统计学意义(P＜0.05).结论 右美托咪啶复合依托咪酯对于胃癌根治术患者具有良好麻醉效果,可减少患者术后疼痛及感染,减少不良反应发生.小剂量右美托咪啶即可发挥作用,故推荐临床使用小剂量治疗方案.     

丙泊酚与依托咪酯联合应用对卵巢癌化疗患者麻醉诱导时血流动力学的影响

目的观察丙泊酚与依托咪酯联合应用对卵巢癌化疗患者诱导插管期间血流动力学的影响。方法 30例接受术前化疗的卵巢癌患者随机分为3组每组10例患者：丙泊酚组（P组）、依托咪酯组（E组）、丙泊酚＋依托咪酯组（PE组）,观察诱导前（T0）、插管前1 min（T1）、插管后即刻（T2）、插管后1 min（T3）、2 min（T4）、5 min（T5）不同时点的血流动力学变化。结果与T0比较,P组T1～5MAP、HR明显降低（均P〈0.05）;E组T2～4MAP、HP明显增快（均P〈0.05）;PE组T1～5MAP、HR差别无统计学意义;3组患者T1～5时BIS值均显著降低（均P〈0.01）。结论麻醉诱导时,联合应用丙泊酚与依托咪酯可更好地维持卵巢癌术前化疗患者的血流动力学稳定。     

丙泊酚、依托咪酯在卵巢癌全麻手术中的效果及对患者循环功能的影响

目的 探讨丙泊酚联合依托咪酯在卵巢癌全麻手术中的麻醉诱导效果及对患者血液循环系统的影响.方法 选取实施全麻手术治疗的300例卵巢癌患者进行回顾性分析,其中丙泊酚麻醉诱导100例(丙泊酚组)、依托咪酯麻醉诱导100例(依托咪酯组)、丙泊酚联合依托咪酯麻醉诱导100例(联合组),对比3组患者不同时间点的收缩压(SBP)、舒张压(DBP)、心率(HR)、血氧饱和度(SpO2)变化,对比3组的气管插管条件Coopers评分、肌松起效时间差异.结果 T0时刻,丙泊酚组、依托咪酯组和联合组的SBP、DBP、HR及SpO2测定值比较,差异无统计学意义(P﹥0.05);T2、T3、T4时刻,丙泊酚组患者的SBP、DBP、HR及SpO2测定值低于联合组(P﹤0.05);T3、T4时刻,依托咪酯组的SBP、DBP、HR测定值高于联合组(P﹤0.05),SpO2测定值低于联合组(P﹤0.05);丙泊酚组、依托咪酯组和联合组的Coopers评分比较,差异无统计学意义(P﹥0.05);依托咪酯组和联合组的肌松效应起效时间短于丙泊酚组,差异有统计学意义(P﹤0.05),依托咪酯组和联合组的肌松效应起效时间比较,差异无统计学意义(P﹥0.05).结论 采用丙泊酚联合依托咪酯在全麻卵巢癌手术中实施麻醉诱导,在保证肌松效应起效快、插管效果好的情况下,对患者血流动力学的影响更小.     

依托咪酯和丙泊酚在良性乳腺肿瘤手术中的应用

目的 探讨依托咪酯和丙泊酚在良性乳腺肿瘤手术中的应用。方法 选择60例良性乳腺肿瘤手术患者,随机分为2组,每组30例(n=30),分别为依托咪酯组(E组),丙泊酚组(P组),两组均静注咪达唑仑2 mg~3 mg,E组患者静脉靶控输注依托咪酯,设定的效应室浓度为0.3 μg/mL;P组患者静脉靶控输注异丙酚,设定效应室浓度为3 μg/mL,两组在输注依托咪酯或丙泊酚同时靶控输注舒芬太尼0.1 ng/mL。观察并记录患者术中血流动力学变化,呼吸抑制、肌震颤及术后恶心呕吐情况。结果 与P组相比,E组的血流动力学变化明显平稳(P＜0.05);呼吸抑制情况明显减轻(P＜0.05);两组病人肌震颤情况无统计学差异(P＞0.05);E组恶心呕吐发生率较P组高(P＜0.05)。结论 靶控输注依托咪酯或异丙酚均可安全应用于乳腺良性肿瘤麻醉,依托咪酯对血流动力学及呼吸的影响较丙泊酚小,但其术后恶心呕吐的发生率较高。     

力月西、惜 内酚和依托咪酯用于全麻诱导的临床观察

目的探讨力月西、异丙酚和依托咪酯全麻诱导与气管插管对血流动力学的影响.方法60例择期上腹部肿瘤手术患者随意分三组.A组全麻诱导;力月西0.2mg·kg-1.B组全麻诱导异丙酚2mg·kg-1.C组全麻诱导依托咪酯0.3mg·kg-1.连续观察监测麻醉前、麻醉诱导给药前,插管后1min、插管后5min时MAP和HR变化,并记录麻醉诱导起效时间和并发症.结果A组全麻诱导对血流动力学影响平稳,起效慢于B、C组.B组全麻诱导对循环有一过性抑制,苏醒时间快.C组全麻诱导平稳但可引起注射部位疼痛和肌颤.结论力月西全麻诱导对血流动力学影响很少,比较适合于心脏功能储备差的患者全麻诱导气管插管.     

胶质瘤的起源细胞与神经干细胞的关系

神经干细胞在成人脑中分离培养成功,向胶质瘤起源细胞的传统学说发出了挑战.神经节胶质细胞瘤、少突星形细胞瘤等可能来自相应的前体细胞、神经干细胞移植后的潜在致瘤性、神经干细胞转基因后变为胶质瘤,这些实验结果支持胶质瘤起源于中枢神经内的具有增殖和分化潜能的干细胞或前体细胞,但尚未找到确凿的直接证据.进一步研究神经干细胞的分化及其分子机制,将有望从根本上解决胶质瘤的起源细胞这一问题,为胶质瘤的治疗提供新的希望.     

转染Cx43cDNA对胶质瘤细胞生长影响的观察

背景与目的：缝隙连接与肿瘤的发生、发展、转移和凋亡密切相关。本研究观察转染Cx43cDNA对C6细胞缝隙连接细胞间通讯功能（gap iunctional intercellular communication，GJIC）功能及生长影响情况。方法：①通过氯化钙法将质粒转入JM109菌株，筛选阳性菌落扩增，用Wizard Pure Fection质粒DNA纯化系统试剂盒进行提取及纯化，最后用Ecor Ⅰ、Hind Ⅲ内切酶进行酶切鉴定；②基因转染：通过Lipofect AMINE2000介导对C6细胞进行质粒DNA转染，用G418筛选浓度筛选出转染成功细胞：③用半定量RT—PCR检测转染后c6细胞Cx43mRNA表达的改变；④划痕荷载染料传输实验（scrape loading dye transfer test，SLDT）检测转染前后GJIC的改变；⑥以MTT法检测转染细胞培养72h后的A值，观察转染Cx43cDNA对C6细胞生长抑制情况；⑥用流式细胞仪技术检测转染细胞培养72h后细胞凋亡率，观察转染Cx43cDNA对C6细胞凋亡的影响。结果：①转染了Cx43cDNA的C6-Cx43细胞Cx43mRNA表达显著增加；②C6-Cx43细胞染料传输能力较空载质粒转染细胞C6-Non明显增强；⑧MTT法检测表明同C6-Non相比，C6-Cx43细胞A值较低，两者差异有显著性（P〈0．01）；④流式细胞仪检测发现C6-Cx43与C6-Non细胞凋亡率无显著性差异（P〉0．05）。结论：①转染Cx43cDNA可上调c6细胞GJIC水平。②转染Cx43cDNA可显著抑制C6细胞生长，但细胞凋亡并未增加。     

沙利度胺对前列腺癌PC-3细胞的增殖及细胞缝隙连接通讯的影响

  目的  观察沙利度胺对前列腺癌PC-3细胞增殖和凋亡的作用及对PC-3细胞中Cx43表达水平的影响。   方法  将处于对数生长期的前列腺癌PC-3细胞分别给予递增浓度的沙利度胺(0、12.5、25、50、100μg/mL)处理24 h和48 h。采用CCK-8法检测不同浓度沙利度胺对PC-3细胞的增殖抑制影响, Annexin V-FITC/PI双染色法检测细胞凋亡情况, RT-PCR法检测Cx43mRNA的表达及Westernblot检测Cx43蛋白的表达。   结果   沙利度胺浓度在25~100μg/mL能明显抑制PC-3细胞体外增殖, 随着时间、浓度增加, 抑制率相应升高。不同浓度组沙利度胺处理PC-3细胞24~48 h后, Cx43 mRNA和蛋白有不同程度的升高(P < 0.05)。   结论  沙利度胺可通过抑制人前列腺癌PC-3细胞增殖、诱导其凋亡, 产生抗肿瘤作用。沙利度胺可上调前列腺癌PC-3细胞Cx43mRNA及蛋白的表达水平, 并可能促进前列腺癌PC-3细胞的细胞缝隙连接通讯功能的恢复, 从而抑制肿瘤生长。      

转染连接蛋白基因对人脑胶质瘤细胞间隙连接通讯及其生长变化的研究

目的 研究连接蛋白（Cx)基因对人脑胶质瘤细胞的细胞间隙连接通讯（GJIC）及其增殖的抑制作用,探索以Cx43基因治疗胶质瘤的可行性。方法 将含Cx43cDNA的质粒,以脂质体介导转染Cx43表达缺失的TJ905人胶质母细胞瘤细胞,通过Northern印染杂交、原位杂交及免疫组化染色检测Cx43mRNA及蛋白表达,划痕标记荧光染料示踪技术（SLDT）检测GJIC,MTT法测定细胞增殖率,核仁组成区嗜银蛋白（AgNOR)染色检测细胞增殖活性,TUNEL法检测细胞凋亡。结果 转染后TJ905细胞有不同程度的Cx43mRNA和蛋白表达及GJIC恢复。Cx43表达水平高的克隆细胞增殖明显下降,细胞凋亡并未增加。结论 Cx43基因及GJIC在恶性胶质瘤的发生发展过程中起重要作用,可能成为恶性胶质瘤基因治疗的优选靶的之一。     

STUDIES ON THE GAP JUNCTIONAL INTERCELLULARCOMMUNICATION OF HUMAN NASOPHARYNGEALCARCINOMA CELLS AND THE EFFECT OF RII

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Inhibitory effect of pentachlorophenol on gap junctional intercellular communication in rat liver epithelial cells in vitro

To understand the initiating/promoting actions of pentachlorophenol (PCP), a non-mutagenic hepatocarcinogen, and its metabolite, tetrachlorohydroquinone (TCHQ), we investigated the effects of each chemical on gap junctional intercellular communication (GJIC) in rat liver epithelial cells (WB cells) by the scrape-loading and dye transfer method. After treatment with PCP, the GJIC was initially inhibited at 4 h but was restored in 6–8 h, followed by a second phase of inhibition between 16 and 24 h. Both the first and second inhibitions were concentration-dependent and were restored by 2–4 h after removal of PCP. The phosphorylation state of connexin 43 (CX43) and its localization on the plasma membrane were unchanged up to 24 h after treatment; however, this was accompanied by a decrease in the CX43 protein level. No inhibitory effect was apparent on the GJIC of cells treated with TCHQ. These results suggest that PCP may play a critical role of promoting activity via non-mutagenic mechanisms.     

Reduction in gap junction intercellular communication promotes glioma migration

Glioblastoma Multiforme (GBM), an aggressive form of adult brain tumor, is difficult to treat due to its invasive nature. One of the molecular changes observed in GBM is a decrease in the expression of the gap junction protein Connexin43 (Cx43); however, how a reduction in Cx43 expression contributes to glioma malignancy is still unclear. In this study we examine whether a decrease in Cx43 protein expression has a role in enhanced cell migration, a key feature associated with increased tumorigenicity. We used a 3D spheroid migration model that mimics the in vivo architecture of tumor cells to quantify migration changes. We found that down-regulation of Cx43 expression in the U118 human glioma cell line increased migration by reducing cell-ECM adhesion, and changed the migration pattern from collective to single cell. In addition gap junction intercellular communication (GJIC) played a more prominent role in mediating migration than the cytoplasmic interactions of the C-terminal tail. Live imaging revealed that reducing Cx43 expression enhanced relative migration by increasing the cell speed and affecting the direction of migration. Taken together our findings reveal an unexplored role of GJIC in facilitating collective migration.     

洛伐他汀对 MCF-7细胞增殖分化功能及间隙连接细胞通讯的影响

背景与目的:洛伐他汀( lovastatin)是细胞内源性胆固醇合成的抑制剂,临床已普遍用于治疗高脂血症.现有研究报道,洛伐他汀具有抗肿瘤作用,但分子机制尚不清楚.本文探讨洛伐他汀对人乳腺癌细胞 MCF-7增殖功能以及间隙连接细胞通讯( gap junctional intercellular communication,GJIC)的影响.方法:分别以 4、 8、 16 μ mol/L洛伐他汀处理 MCF-7细胞 24～ 72 h后,流式细胞仪检测细胞周期的时相分布及细胞凋亡率,硝基蓝四氮唑( NBT)还原实验鉴定细胞分化,并采用划痕标记染料示踪技术观察洛伐他汀对 MCF-7细胞 GJIC功能的影响.结果:不同浓度洛伐他汀处理细胞不同时间后, MCF-7细胞的增殖明显受抑,抑制率最高可达 75.8%,且同一处理时相点各组间比较差异均有显著性 (P< 0.05);细胞周期分析显示,各处理组内 G0/G1期细胞明显增多,处理 72 h后可高达 80%左右;同时洛伐他汀能明显促进 MCF-7细胞分化、各处理组间比较差异均有显著性 (P< 0.01),但洛伐他汀诱导该细胞凋亡的作用不明显.另外,洛伐他汀有上调或恢复 MCF-7细胞 GJIC的作用; 16 μ mol/L洛伐他汀处理细胞 72 h后,荧光染料传输的范围可达 4～ 5层细胞.以上作用均有浓度-效应和时间依赖关系.结论:洛伐他汀可抑制 MCF-7细胞增殖,使细胞生长阻滞于 G0/G1期,并能促进细胞分化,该作用可能与洛伐他汀上调或恢复 MCF-7细胞的 GJIC功能有关.     

Modulation of gap junctional intercellular communication by EGF in human kidney epithelial cells

Modulation of gap junctional intercellular communication (GJIC)was studied in a multistep model of human renal epithelial carcinogenesis.We report that the majority of primary human kidney epithelialcells (NHKE) grown from fetal kidney explants did not communicatethrough gap junctions. Communication could, however, be observedwithin a subpopulation of the cells. Ni(II)-immortalized cells(IHKE) showed GJIC at a level of 10–20 communicating cells,but with heterogeneous regions on the dish, with regard to bothcommunication and distribution of connexin43. The heterogeneitywas less pronounced in a ras-transfected tumourigenic cell line(THKE), which also showed communication of     

辛伐他汀对肝癌细胞间缝隙连接功能的影响研究

背景与目的：肝癌的发生、发展过程中伴随着细胞间缝隙连接(gap junction,GJ)功能的下降,恢复或增强肿瘤细胞间的GJ可以抑制肿瘤细胞的恶性转化和生长增殖。本研究拟通过观察辛伐他汀对肝癌细胞间GJ功能的影响,寻找能够增强GJ功能的药物,从而为肝癌的治疗提供新策略和新手段。方法：采用磺酰罗丹明B法观察辛伐他汀对大鼠肝癌细胞Hep3b的抑制作用;细胞接种荧光法和划痕标记/染料示踪技术观察辛伐他汀对GJ功能的影响。结果：1、5和10 μmol/L辛伐他汀在24 h作用时间内均对细胞生长无抑制作用,将不影响GJ的数量;取5、10 μmol/L辛伐他汀作用细胞4 h后,与对照组相比,GJ的荧光传递功能明显增强;与对照组相比,5、10 μmol/L辛伐他汀作用细胞4 h后,荧光黄染料(lucifer yellow,Ly,Sigma)传输范围随着辛伐他汀浓度的升高逐渐增大。结论：辛伐他汀可以增强肝癌细胞GJ功能。     

Gap junctional intercellular communication of primary and asbestos-associated malignant human mesothelial cells

We examined gap junctional intercellular communication (GJIC)of primary human mesothelial cells and cell lines of asbestos-associatedhuman pleural mesotheliomas, and the effect of asbestos andother mineral fibres on these cells. In homologous cultures,the GJIC capacity of six out of seven tumour cell lines wasmarkedly less than for primary mesothelial cells. This defectin GJIC appeared not to be at the expression level of mRNA andprotein of the gene encoding the 43 kDa gap junction protein.In heterologous cocultures of tumour cells and primary mesothelialcells, however, 80–90% of the tumour cell/normal cellcontacts were functional. Exposure of primary mesothelial cellsto TPA, a phorbol ester tumour promoter, resulted in markedinhibition of GJIC, being an action common to numerous tumourpromoters. Such an effect though was not observed with the carcinogenicmesothelioma-inducing mineral fibres chrysotile and amosite,neither with glass wool. These results suggest that a permanentdefect in GJIC capacity is a common feature of human mesotheliomacells, but how mineral fibres are involved in the process ofmesotheliomagenesis is still unclear.     

Suppressed gap junctional intercellular communication in carcinogenesis of endometrium.

To examine whether and at which stage of endometrial carcinogenesis decreased connexin expression occurs, we investigated changes in the expression of the gap junction proteins, connexin 26 (Cx26), Cx32 and Cx43, in human endometrial hyperplasia and cancer samples. Forty-eight endometrial tissue samples (15 endometrial hyperplasias and 33 endometrial cancers) were subjected to immunofluorescence and RT-PCR analysis. In endometrial hyperplasia, Cx26 was aberrantly expressed in all samples as revealed immunohistochemically. There was weak or negative expression in 12 samples (80.0%) and diffuse expression in cytoplasm in 3 samples (20.0%). Cx32 expression in those samples was similar to that of Cx26; there was weak or negative expression in 11 samples (73.3%) and diffuse expression in 4 samples (26.7%). In endometrial cancer, Cx26 was expressed weakly or negatively in 25 samples (75.8%), diffusely in 6 samples (18.2%) and normally in 2 samples (6.1%), while Cx32 was expressed weakly or negatively in 26 samples (78.8%), diffusely in 5 samples (15.2%) and normally in 2 samples (6.1%). It was confirmed that weak staining of Cx26 and Cx32 was due to poor expression of their mRNA. All samples showed weak Cx43 protein expression as revealed by immunohistochemical analysis. In the majority of samples, concomitant expression levels of Cx26 and Cx32 protein were observed, confirming our long-term hypothesis that Cx26 and Cx32 are both abnormally regulated in a coordinated fashion in the endometrium. Our results indicate that during endometrial carcinogenesis, loss of gap junctional intercellular communication (GJIC) may occur due to the suppressed expression and the aberrant localization of connexin at relatively early stages.     

Direct gap junction communication between malignant glioma cells and astrocytes

Gap junctions are intercellular channels that connect the interiors of coupled cells. We sought to determine the extent to which malignant glioma cells form gap junction channels with astrocytes from either adult human brain or rat forebrain. The astrocytic gap junction protein, connexin 43 (Cx43), was identified in immunoreactive plaques at areas of cell-to-cell contact between cocultured glioma cells and astrocytes. These gap junction plaques were composed of functional channels, because extensive dye coupling was evident between the glioma cells and astrocytes from both human and rat brain. Calcium signaling was also readily transmitted from glioma cells to astrocytes and vice versa. In live rat brain, injection of glioma cells prelabeled with the gap junction tracer, dicarboxy-dichlorofluorescein, revealed extensive dye transfer to host cells, demonstrating that malignant glioma cells directly couple with normal brain cells. These observations suggest that intercellular communication via gap junctions may play a role in regulating cellular interactions during tumor invasion. In fact, the presence of gap junctions between astrocytes and glioma cells was sufficient to induce a transformation of astrocytic phenotype. Astrocytes cocultured with C6 glioma cells overexpressing Cx43 were significantly smaller and expressed a lower level of glial fibrillary acidic protein than astrocytes cocultured with otherwise identical mock-transfected, gap junction-deficient C6 cells. Thus, direct cellular coupling with glioma cells result in a phenotypic transformation of astrocytes that may contribute to the susceptibility of surrounding tissue to glioma invasion.