重楼活性单体PP-22对人结肠癌SW620细胞增殖和凋亡的影响

目的 探讨重楼活性单体PP-22对人结肠癌SW620细胞增殖和凋亡的影响及其联合5-氟尿嘧啶(5-FU)和洛铂的抗肿瘤效果。方法 采用噻唑蓝(MTT)法和克隆形成抑制实验观察不同浓度PP-22对人结肠癌SW620细胞增殖的抑制作用;分别观察PP-22联合5-FU和洛铂对人结肠癌SW620细胞增殖的抑制作用;碘化丙锭单染流式细胞术检测细胞周期变化及细胞凋亡水平;Western blot法检测PP-22作用后细胞凋亡相关蛋白的表达。结果 重楼单体PP-22能显著抑制SW620细胞的生长,作用呈剂量-效应关系;随着PP-22浓度的增加,细胞克隆形成逐渐减少,与细胞对照组和DMSO组相比有显著差异;PP-22联合不同浓度的5-FU和洛铂作用于SW620细胞48 h,可提高SW620细胞对5-FU和洛铂的敏感性;不同浓度PP-22作用于SW620细胞后,细胞周期阻滞于S期;PP-22作用后存在Caspase-3和Caspase-9蛋白的活化和降解,抗凋亡蛋白Bcl-2、Bcl-xL减少,促凋亡蛋白Bax的表达增加。结论 PP-22能显著抑制人结肠癌SW620细胞增殖,诱导细胞凋亡,提高SW620细胞对5-FU和洛铂的敏感性。     

LncRNA GAS5对结直肠癌5-FU耐药的作用研究

目的 探讨长链非编码RNA生长停滞特异性转录本5(LncRNA GAS5)对结直肠癌5-氟尿嘧啶(5-FU)耐药的作用。方法 选取人结肠癌细胞系HCT-8和SW480,建立5-FU耐药细胞株,构建LncRNA GAS5过表达结直肠癌细胞模型。反转录-聚合酶链式反应(RT-PCR)检测LncRNA GAS5在结直肠癌5-FU耐药细胞系中表达;CCK-8检测细胞增殖;流式细胞术检测细胞凋亡。结果 RT-PCR检测显示, LncRNA GAS5在结直肠癌HCT-8细胞与SW480细胞中的表达水平低于正常结肠细胞,差异有统计学意义(P<0.05);LV5-GAS5组HCT-8细胞、SW480细胞中LncRNA GAS5表达高于Vector组,差异有统计学意义(P<0.05)。CCK-8实验检测显示, LncRNA GAS5能明显抑制HCT-8细胞和SW480细胞的增殖(P<0.05)。AnnexinV/PI双重染色及流式细胞术结果显示,在结直肠癌HCT-8细胞与SW480细胞中LV5-GAS5组的细胞凋亡比例高于Vector组,差异有统计学意义(P<0.05)。结论 L...     

丁酸钠增强5-aza-dC对人胃癌MKN-28细胞生长的抑制作用

目的 探讨丁酸钠(NaB)和5-氮-2'-脱氧胞苷(5-aza-dC)对胃癌细胞MKN-28细胞生长抑制的协同作用.方法 MKN-28细胞分为5-aza-dC组(A组)、NaB组(B组)、5-aza-dC+NaB组(C组)和对照组(D组).四甲基偶氮唑盐比色(MTT)法观察人胃癌MKN-28细胞生长,流式细胞术检测细胞周期及细胞凋亡.结果 C组对MKN-28细胞的生长抑制作用明显强于A、B组(P<0.05);A组对细胞周期无影响,而B组及C组均可使细胞周期阻滞于G0/G1期(P<0.05);C组诱导的细胞凋亡率明显高于A、B组[(33.7±3.1)%vs.(8.3±1.3)%、(20.8±2.4)%](P<0.05).结论 NaB可增强5-aza-dC对人胃癌MKN-28细胞的生长抑制作用,此协同作用可能与阻滞细胞周期及诱导细胞凋亡有关.     

长链非编码 RNA母系表达基因 8靶向微小 RNA-497-5p调控血管瘤血管内皮细胞的增殖和凋亡

目的 探讨长链非编码RNA母系表达基因8(MEG8)靶向微小RNA(miR)-497-5p对血管瘤血管内皮细胞的增殖和凋亡的影响.方法 实时荧光定量逆转录聚合酶链反应(qRT-PCR)检测河南中医药大学第一附属医院2017年1月至2018年6月收集的52例血管瘤组织和与其对应的瘤旁正常皮肤组织中MEG8和miR-497-5p的表达水平.血管瘤血管内皮细胞HemEC分为si-NC组、si-MEG8组、miR-NC组、miR-497-5p组、si-MEG8+anti-miR-NC组、si-MEG8+anti-miR-497-5p组.四甲基偶氮唑盐微量酶反应比色法(MTT法)检测细胞活力,流式细胞术检测细胞凋亡率,蛋白质印迹法(Western blotting)检测细胞周期蛋白D1(cyclin D1)和P21、B细胞淋巴瘤-2(Bcl-2)和Bcl相关X(Bax)蛋白的表达水平.双荧光素酶报告基因实验验证MEG8和miR-497-5p的靶向关系.结果 与瘤旁正常皮肤组织相比,血管瘤组织中MEG8表达水平[(0.82±0.08)比(0.33±0.03)]升高(P<0.05),miR-497-5p表达水平[(0.34±0.03)比(0.84±0.08)]降低(P<0.05).与si-NC组比较,si-MEG8组HemEC细胞存活率[(39.61±4.06)％比(103.50±11.04)％]、cyclin D1和Bcl-2蛋白表达降低(P<0.05),凋亡率[(26.57±2.73)％比(8.33±0.85)％]、P21和Bax蛋白表达升高(P<0.05).与miR-NC组比较,miR-497-5p组HemEC细胞存活率[(48.87±5.09)％比(104.11±10.64)％]、cy?clin D1和Bcl-2蛋白表达降低(P<0.05),凋亡率[(21.26±2.45)％比(8.33±0.85)％]、P21和Bax蛋白表达升高(P<0.05).MEG8和miR-497-5p直接特异性结合.与si-MEG8+anti-miR-NC组比较,si-MEG8+anti-miR-497-5p组HemEC细胞存活率[(86.10±8.81)％比(40.23±4.35)％]、cyclin D1和Bcl-2蛋白表达升高(P<0.05),凋亡率[(15.32±1.67)％比(26.81±2.94)％]、P21和Bax蛋白表达降低(P<0.05).结论 抑制MEG8通过靶向miR-497-5p能够抑制血管瘤血管内皮细胞增殖,促进细胞凋亡,进而遏制血管瘤的发生发展.     

雷公藤内酯醇降调胰腺癌细胞5-脂氧合酶表达作用研究

目的探讨雷公藤内酯醇（TL）对胰腺癌细胞中5 脂氧合酶(5 LOX)蛋白表达及胰腺癌细胞凋亡的影响。方法应用RT PCR法和免疫细胞化学法检测胰腺癌细胞株SW1990中5 LOX表达，同时应用流式细胞术检测胰腺癌细胞SW1990的凋亡指数。结果胰腺癌细胞株SW1990表达5 LOX，正常胰腺组织不表达； TL可抑制SW1990中5 LOX表达，并促进胰腺癌细胞SW1990凋亡，作用随浓度的增加而增强(P＜0.01)；细胞凋亡与5 LOX蛋白的表达相关(P＜0.01)。结论TL可抑制胰腺癌细胞SW1990中5 LOX的表达，并促进胰腺癌细胞凋亡     

白头翁皂苷A3通过M2型巨噬细胞提高人结肠癌SW480细胞对5-FU的化疗敏感性

目的:观察白头翁皂苷A3(A3)通过干预巨噬细胞极化增强人结肠癌SW480细胞对5-氟尿嘧啶(5-FU)化疗的敏感性,并探讨其作用机制。方法:采用CCK8法检测A3对人单核THP-1细胞存活率的影响,确定A3的安全作用浓度;采用佛波酯(PMA)诱导THP-1细胞分化为M0型巨噬细胞,将M0型巨噬细胞分为M0对照组,M2模型组,A3低、中、高剂量干预组。其中M2模型组给予20 μg·L^-1IL-4与20 μg·L^-1IL-13进行造模,A3干预组在造模的同时给予低、中、高剂量(50,75,100 mg·L^-1)A3进行干预。采用流式细胞术检测M2型巨噬细胞表面抗原CD206的表达;采用RT-PCR法检测M2型巨噬细胞极化因子CD206、IL-10、CCL22、CCL18 mRNA的表达;采用Western blot法检测细胞内p-STAT6、CD206、IL-10、CCL22蛋白的表达。A3干预巨噬细胞M2型极化后的细胞上清液作为条件培养基用于考察SW480细胞对5-FU的化疗敏感性,采用CCK8法检测SW480细胞的存活率;采用Annexin-FITC/PI双染法及Western blot法检测SW480细胞凋亡水平,以及Bax、Cleaved Caspase-3蛋白的表达。结果:A3在50,75,100 mg·L^-1浓度时对THP-1细胞存活率没有显著影响。A3呈剂量依赖性减少CD206阳性细胞表达比例,下调p-STAT6、CD206、IL-10、CCL22、CCL18基因与蛋白的表达(P<0.05,P<0.01)。A3干预巨噬细胞M2型极化后的条件培养基显著提高了SW480细胞对5-FU的敏感性,表现为SW480细胞的存活率下降、凋亡率升高,以及促凋亡蛋白Bax、Cleaved Caspase-3表达上调(P<0.05)。结论:A3能够减弱M2型巨噬细胞对SW480细胞凋亡的抑制作用从而提高SW480细胞对5-FU的化疗敏感性,作用机制可能与A3调控STAT6信号通路抑制巨噬细胞M2型极化有关。     

姜黄素体内外逆转结肠癌的5-氟尿嘧啶耐药研究及机制探讨

摘要：目的 探究姜黄素在体内外对结肠癌5-氟尿嘧啶（5-FU）耐药的逆转作用及其相关机制。 方法 以SW480结肠癌细胞为亲代细胞,构建5-FU耐药细胞株SW480R,采用MTT法检测SW480R细胞的耐药指数以及不同浓度的姜黄素对SW480R细胞增殖能力的影响;流式细胞术检测姜黄素对SW480R细胞周期和凋亡的影响;Western blot检测姜黄素对SW480R细胞上皮-间充质转化（epithelial-mesenchymal transition, EMT）相关蛋白以及Wnt信号通路相关蛋白的影响;采用裸鼠移植瘤模型检测肿瘤体积变化情况,计算姜黄素的体内抑瘤率,Western blot检测肿瘤组织中相关蛋白变化。结果 SW480R的耐药指数为12.16,姜黄素能够剂量依赖性地抑制SW480R细胞的增殖,阻滞SW480R细胞周期于G0/G1期,以及诱导SW480R细胞凋亡;Western blot结果表明姜黄素能够在体内外抑制EMT和Wnt信号通路的活性;体内实验表明姜黄素能够有效抑制裸鼠移植瘤的生长。结论 姜黄素能够在体内外逆转结肠癌的5-FU耐药,其机制可能是通过调控Wnt信号通路从而抑制EMT的发生。     

瘦素对5-氟尿嘧啶损伤结肠癌细胞的影响

目的探讨不同浓度的瘦素对5-氟尿嘧啶(5-FU)损伤结肠癌细胞的影响。方法同时用5-FU及不同浓度的瘦素进行体外干预结肠癌HT-29细胞株。MTT法检测5-FU50%细胞生长抑制率(IC50)的变化。流式细胞仪、原位末端转移酶标记法(TUNEL)进行周期及凋亡分析。以RT-PCR方法检测caspase-9,caspase-3mRNA的表达。结果瘦素抑制5-FU对HT-29的杀伤作用。抑制5-FU诱导的细胞周期阻滞及细胞凋亡。RT-PCR表明加入瘦素后caspase-9,caspase-3mRNA的表达均下降,且呈剂量依赖性。结论瘦素通过下调caspase-9,caspase-3的表达促进结肠癌细胞产生凋亡抵抗,抑制5-FU的损伤作用。     

长链非编码 RNA膀胱癌相关转录物 1对微小 RNA-503-5p的靶向关系及对结直肠癌细胞增殖和凋亡的影响

目的 研究长链非编码RNA(lncRNA)膀胱癌相关转录物1(BLACAT1)对微小RNA(miR)-503-5p的靶向关系及结直肠癌细胞增殖和凋亡的影响.方法 实时荧光定量PCR(qRT-PCR)检测结肠癌细胞株SW620,LOVO,HT29和人正常结肠黏膜上皮细胞株NCM460中BLACAT1和miR-503-5p的表达.在HT29细胞中转染si-BLACAT1、pcDNA-BLACAT1或miR-503-5p,噻唑蓝(MTT)检测细胞增殖,流式细胞术检测细胞凋亡,蛋白质印迹法(Western blotting)检测细胞核相关抗原Ki-67(Ki-67)、细胞周期蛋白D1(Cyclin D1)、活化的多聚ADP-核糖聚合酶(Cleaved PARP)和活化的含半胱氨酸的天冬氨酸蛋白水解酶-3(Cleaved caspase-3)的表达,starbase预测和双荧光素酶报告分析BLACAT1与miR-503-5p之间的靶向关系.si-BLACAT1和anti-miR-503-5p共转染,观察干扰miR-503-5p对沉默BLACAT1诱导的结直肠癌细胞增殖和凋亡的影响.结果 与NCM460细胞比较,SW620、LOVO和HT29中BLACAT1表达量明显增加[(4.93±0.58)、(5.66±0.53)、(6.17±0.66)比(1.03±0.22)],miR-503-5p表达量减少[(0.72±0.11)、(0.67±0.09)、(0.51±0.08)比(1.04±0.14)](P<0.05).沉默BLACAT1或转染miR-503-5p明显减少HT29细胞的细胞存活率、Ki-67、CyclinD1蛋白表达量,提高细胞凋亡率、Cleaved PARP和Cleaved caspase-3蛋白水平(P<0.05),过表达BLACAT1则反之.BLACAT1靶向miR-503-5p调控其表达.干扰miR-503-5p部分逆转沉默BLACAT1抑制结直肠癌细胞增殖、Ki-67、CyclinD1蛋白表达和诱导结直肠癌细胞凋亡、Cleaved PARP、Cleaved caspase-3蛋白表达的作用.结论 lncRNA BLA-CAT1在表达上调,沉默BLACAT1可通过靶向调控miR-503-5p的表达,来抑制结直肠癌细胞增殖,并诱导细胞凋亡.     

5-氟尿嘧啶联合蒽贝素治疗结肠癌的研究

目的：探讨5-氟尿嘧啶（5-FU）联合蒽贝素对结肠癌的治疗作用。方法：MTT法和肿瘤球生长实验考察5-FU联合蒽贝素对结肠癌C26细胞的毒性。建立结肠癌小鼠移植瘤模型,随机分为生理盐水组、5-FU组、蒽贝素组和联合给药组。各组小鼠均3d一次尾静脉注射给药。观察给药过程中瘤体体积的变化,考察不同给药组对小鼠肿瘤生长的抑制效果。结果：给药48h后生理盐水组肿瘤细胞存活率为95％,5-FU组、蒽贝素组和联合给药组肿瘤细胞存活率分别为48％、69％和18％,与单独给药组相比,联合给药能够显著增强对C26细胞的增殖抑制作用（P〈0．01）。给药7d后,生理盐水组肿瘤球持续生长,体积增大1．52倍,3个给药组肿瘤球体积出现了不同程度的减小,5-FU组、蒽贝素组和联合给药组分别使肿瘤体积减小到原体积的71％、89％和33％（P〈0．01）;生理盐水组、蒽贝素组、5-FU小鼠肿瘤体积成长分别变为给药前肿瘤体积的1．85倍、1．79倍和1．49倍,而联合给药组为1．21倍（P〈0．01）。联合给药组与蒽贝素组和5-FU组单独给药组间差异具有统计学意义（P〈0．01）。同时联合给药能够延长荷瘤小鼠的中位生存期。结论：5-FU与蒽贝素都具有抗结肠癌作用．且二者联合使用效果更显著。     

Kinetic studies with 5-azacytidine-5'-triphosphate and DNA-dependent RNA polymerase.

In order to further understand the biochemical mode of action of 5-azacytidine, a potent antileukemic agent, kinetic studies were performed with 5-azacytidine-5'-triphosphate (5-aza-CTP) and purified DNA-dependent RNA polymerase from Escherichia coli and calf thymus. RNA polymerase could catalyze the incorporation of the fradulent nucleotide, 5-aza-CTP, into RNA. The apparent K_m value for 5-aza-CTP was estimated to be 350 and 390 for the E. coli and calf thymus enzymes respectively. The K_m value for 5-aza-CTP was about 18-fold greater than the K_m value for CTP (20 μM). The apparent V_max value for CTP was about 2-fold greater than the V_max value for 5-aza-CTP. 5-Aza-CTP was a weak competitive inhibitor with respect to CTP; the apparent K_i value for 5-aza-CTP was estimated to be 680 and 810 μM for the E. coli and calf thymus enzymes respectively. On the other hand, CTP was a potent competitive inhibitor with respect to 5-aza-CTP; the apparent K_i value of CTP was estimated to be 16 μM. 5-Aza-CTP did not appear to inhibit the incorporation of UTP into RNA in the reaction catalyzed by RNA polymerase. These data suggest that the inhibition of RNA synthesis in cells by 5-aza-cytidine is not produced by the inhibition of RNA polymerase by 5-aza-CTP.     

Recent developments in C5/C5a inhibitors

Complement factor 5a (C5a) is formed upon complement system activation in response to infection, injury or disease. Whilst C5a is a potent mediator of immune and inflammatory processes, excessive production or inadequate regulation of C5a has been implicated in the pathogenesis of numerous immuno-inflammatory diseases, predominantly through experimental studies utilising animal models of disease. Both acute and chronic conditions may benefit from C5a inhibition, including rheumatoid arthritis, inflammatory bowel disease, asthma, psoriasis, haemorrhagic shock and neurodegenerative conditions. The potentially broad clinical application for treatments that inhibit the activity of C5a at C5a receptors and the large global market for anti-inflammatory therapeutics have made C5a and the C5a receptor attractive targets for academic and commercial drug development programmes. In the past 5 years, interest in C5a as a drug target has grown substantially, and this activity has resulted in a collection of patents and scientific papers reporting novel C5a and C5a receptor inhibitors and antagonists, and generated a secondary stream of patent applications broadly claiming the use of C5/C5a inhibitors as a method of treating various immune and inflammatory conditions. This paper will review the physiology and pathophysiology of C5a and discuss the development of C5a and C5a receptor inhibitors in light of the recent scientific and patent literature.     

注射用脱氧氟尿苷与5-氟尿嘧啶对照治疗恶性肿瘤121例

目的:验证和比较注射用脱氧氟尿苷(5'-DFUR)和5-氟尿嘧啶(5-FU)抗肿瘤疗效和安全性.方法:121例晚期恶性肿瘤患者进行5'-DFUR单药(n=22)或联合化疗(n=99),后者随机分为治疗组(n=54)和5-FU对照组(n=45).5'-DFUR用法为3 000mg·m-2,静脉滴注,d1～d5;5-FU用法为750mg·m-2,静脉滴注,d1～d5;单药和联合化疗组均给药21～28d为1个周期,2个周期为1个疗程.结果:可评价疗效119例患者,单药组有效率13.6%(3/22),各病种之间差异无显著性.联合化疗中,对照组有效率为11.6%(5/43),治疗组有效率为20.4%(11/54),两组之间差异无显著性,既往治疗与否与疗效无明显相关性.单药组主要不良反应为白细胞下降、恶心呕吐、乏力、腹泻、口腔溃疡等.联合化疗组的不良反应主要为骨髓抑制、恶心呕吐、乏力、神经毒性及口腔黏膜损伤等,治疗组和对照组差异无显著性.结论:5'-DFUR单药和联合其他药物对乳腺癌、胃肠道肿瘤均有一定疗效,但与5-FU对照组之间差异无显著性.     

5-Methoxytryptamine and 2-methyl-5-hydroxytryptamine-induced desensitization as a discriminative tool for the 5-HT3 and putative 5-HT4 receptors in guinea pig ileum

Summary Agonist-induced desensitization has been utilized to discriminate and independently isolate the neuronal excitatory receptors to 5-hydroxytryptamine (5-HT) in the guinea pig ileum (5-HT₃ and putative 5-HT₄ receptors). Electrically stimulated longitudinal muscle myenteric plexus preparations, and non-stimulated segments of whole ileum were used. Exposure to 5-methoxytryptamine (10 mol/l) inhibited completely responses to 5-HT at the putative 5-HT₄ receptor without affecting 5-HT₃-mediated responses. Conversely, exposure to 2-methyl-5-HT (10 mol/l) inhibited completely responses to 5-HT at the 5-HT₃ receptor without affecting putative 5-HT₄-mediated responses. The inhibition with 5-methoxytryptamine and 2-methyl-5-HT, either alone or in combination, appeared selective as responses to KCI, DMPP, carbachol, histamine, and substance P were unaffected or only very slightly modified. Furthermore, the pA₂ values for ICS 205–930 at the putative 5-HT₄ (pA₂ = 6.2 to 6.5) and 5-HT₃ (pA₂ = 7.6 to 8.1) receptors (estimated in the presence of 2-methyl-5HT and 5-methoxytryptamine, respectively) were consistent with those estimated in the absence of desensitization.5-Methoxytryptamine, but not 2-methyl-5-HT, suppressed completely but reversibly the concentration-effect curve to renzapride, suggesting that responses to this agent are mediated exclusively via agonism at the putative 5-HT₄ receptor.It is concluded that 5-methoxytryptamine and 2-methyl-5-HT can be utilized as selective probes to discriminate the putative 5-HT₄ receptor from the 5-HT₃ receptor in guinea pig ileum. This finding is of importance as no selective antagonist exists for the putative 5-HT₄ receptor. Furthermore, the presently described method of agonist-induced desensitization and 5-HT receptor discrimination may be useful for the identification and characterization of the putative 5-HT₄ receptor in other tissues and species. Send offprint requests to D. E. Clarke at the above address     

MD5算法研究

随着网络技术的迅速发展,信息加密技术已成为保障网络安全的一种重要手段,加密算法已经成为人们的一个研究热点.本文对MD5算法进行了深入研究,介绍MD5算法的产生背景、应用及其算法流程,并提出了MD5算法的一个改进方案.     

The interaction of some kynurenine pathway metabolites with 5-hydroxytryptophan and 5-hydroxytryptamine

The kynrenine pathway metabolites kynurenine, 3-hydroxykynurenine and xanthurenic acid have been tested against 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP)-induced head twitches in the mouse in a dose-range of 0.5–5.0 mg/kg. Kynurenine and 3-hydroxykynurenine were highly active. Low doses caused marked potentiation of the twitch response to both 5-HT and 5-HTP with increased toxicity of 5-HT. High doses caused antagonism of both responses. Xanthurenic acid was inactive over the same dose range. The effects of kynurenine could not be duplicated in the guinea-pig ileum. The relevance of these results to the involvement of kynurenine pathway metabolites in depressive illness is discussed.     

Mechanism of block by fluoxetine of 5-hydroxytryptamine3 (5-HT3)-mediated currents in NCB-20 neuroblastoma cells

The effect of fluoxetine (Prozac) on 5-hydroxytryptamine(3) (5-HT(3))-mediated currents in NCB-20 neuroblastoma cells was examined using the whole-cell patch-clamp technique. Fluoxetine produced a significant reduction of peak amplitude without altering the activation time course of 5-HT(3)-mediated currents. These effects were concentration-dependent, with an IC(50) value of 4.15 microM. No voltage dependence was evident in fluoxetine's block of 5-HT(3)-mediated currents over the entire voltage range tested. The extent of block by pre-application of fluoxetine was significantly greater than that by co-application. Fluoxetine also increased the apparent rate of current desensitization to 5-HT application. Using a first-order kinetics analysis, the open-channel blocking rate constants were 0.06 microM(-1)s(-1) (k(+1), association rate constant) and 0.05 s(-1) (k(-1), dissociation rate constant), with an apparent K(d) (=k(-1)/k(+1)) of 0.83 microM. This value is close to an IC(50) of 1.11 microM obtained from the reduction in tau, the time constant of desensitization. Intracellular application of fluoxetine for long durations had no effect on the amplitude or kinetics of 5-HT(3)-mediated currents. Similarly, norfluoxetine, the major metabolite of fluoxetine, reduced the peak current, and enhanced the rate of current desensitization in a concentration-dependent manner with an IC(50) of 2.66 microM, indicating that norfluoxetine is more potent than fluoxetine in blocking 5-HT(3)-mediated currents. These results indicate that, at clinically relevant concentrations, fluoxetine and its metabolite, norfluoxetine, block 5-HT(3)-mediated currents in NCB-20 neuroblastoma cells.     

5-Bicycloindoles as 5-HT1D agonists

In this patent, novel 3-(2-aminoethyl)-, 3-(piperidin-4-yl)- and (R)-3- (pyrrolidin-2-ylmethyl) 5-bicycloindole derivatives are claimed. They are claimed to be agonists at the 5-HT_1D receptors useful for the treatment of 5-HT_1D-mediated disorders such as migraine. The preparation of the compounds is illustrated by six schemes and exemplified by eight examples.The compounds were tested for their inhibition of [³H]-5-HT binding at 5-HT_1D and 5-HT_1B receptors. The compounds are stated to bind selectively to the 5-HT_1D receptor, relative particularly to the 5-HT_1B receptors.     

苦参素对实验性自身免疫性脑脊髓炎大鼠CCL5、CCR5及CCR5mRNA表达的影响

目的:观察苦参素对实验性自身免疫性脑脊髓炎(EAE)大鼠血清中趋化因子CCL5和脊髓中趋化因子CCL5相应的受体(CCR5)及CCR5mRNA表达的影响,探讨苦参素对EAE大鼠的防治机制。方法:用豚鼠全脊髓匀浆和完全弗氏佐剂混合制成抗原乳剂,诱导EAE模型,将40只Wistar大鼠随机分为正常组、模型组、苦参素低剂量组(150mg·kg^-1)、苦参素高剂量组(250mg·kg^-1),苦参素高、低剂量组均连续腹腔给药16d,同期正常组和模型组腹腔注射等量生理盐水,观察大鼠体质量变化,神经功能学评分,进行HE及C-2R-BG病理染色,用ELISA法测定大鼠血清中CCL5的含量、免疫组化法检测大鼠脊髓组织中CCR5的阳性表达、RT-PCR法检测脊髓中CCR5mRNA的表达。结果:苦参素高、低剂量组大鼠的体质量均高于模型组(P<0.05),神经功能学评分,炎症浸润和髓鞘脱失评分,血清中CCL5的水平,脊髓中CCR5、CCR5mRNA的表达均低于模型组(P<0.05),且高低剂量组有组间差异(P<0.05)。结论:苦参素对EAE大鼠具有一定的防治作用,其作用机制可能与下调大鼠CCL5、CCR5及CCR5mRNA的表达有关。     

补体C5a、C5a受体及其拮抗剂的研究进展

C5a是最重要的补体活化产物之一,它与相应的C5a受体结合被激活后,参与了多种疾病的病理过程,如急性肺损伤、脓毒血症、类风湿性关节炎、肾小球肾炎等疾病。如何阻断C5a信号的下传,从而减轻炎症反应一直是免疫学研究的热点问题。目前C5a和C5a受体的拮抗剂主要分为抗C5a抗体、小分子拮抗剂、C5a反义肽、C5a突变体和细菌来源的趋化抑制蛋白等。本文着重介绍C5a和C5a受体的结构与功能,以及相关拮抗剂的研究进展。