肝细胞生长因子和基质金属蛋白酶-9在过敏性紫癜中表达的意义

目的:探讨肝细胞生长因子(HGF)和基质金属蛋白酶-9(MMP-9)在儿童过敏性紫癜(HSP)中表达的意义,探寻肾脏损害预测的敏感指标。方法:选取HSP与过敏性紫癜肾炎(HSPN)患儿各30例,并选取同期体检的健康儿童30名作为对照组,采用酶联免疫吸附试验法(ELISA)检测3组血清和尿液中的HGF及血清MMP-9含量,并采用比浊法检测24 h尿蛋白,分析HGF、MMP-9与24 h尿蛋白的相关性。结果:HSP组、HSPN组血清、尿液HGF,血清MMP-9及尿蛋白定量均高于对照组(P0.05);HSPN组中Ⅱ~Ⅳ期患者血清HGF及Ⅰ~Ⅳ期尿液HGF、Ⅲ~Ⅳ期MMP-9及Ⅰ~Ⅳ期尿蛋白定量均高于HSP组(P0.05);血清及尿液HGF与血清MMP-9无明显相关性(r=0.014,0.027,P0.05);血清HGF与尿蛋白定量无明显相关性(r=0.032,P0.05);尿液HGF、血清MMP-9与尿蛋白定量均呈正相关(r=0.412、0.302,P0.05)。结论:尿液HGF、MMP-9均参与HSP、HSPN病情的发展,尿液HGF、MMP-9水平的监测有助于评估HSPN的病情及预后,但HGF与MMP-9之间无明显相关性。     

儿童过敏性紫癜血清IL-21、TGF-β1、TNF-α、IgA1的变化与紫癜性肾炎发生的相关性研究

探讨儿童过敏性紫癜(henoch-schonlein purpura,HSP)患儿血清中白细胞介素-21(Interleukin-21,IL-21)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、免疫球蛋白A1(Immunoglobulin A1,Ig A1)和转化生长因子-β1(Transforming growth factor-β1,TGF-β1)的含量变化,并研究这些因子与HSP发展为紫癜性肾炎(Henoch-SchOnlein purpura nephritis,HSPN)的相关性。选取我院2015年1月~2016年1月确诊的急性期过敏性紫癜患儿共72例作为本研究的实验对象。根据HSP患儿病症是否累积到肾脏,再分为普通HSP组(39例)和HSPN组(33例),另对照组为30例同期健康体检儿童。通过酶联免疫吸附(ELISA法)对检测血清中白细胞介素-21、转化生长因子-β1以及肿瘤坏死因子-α含量,采用全自动化生化分析仪检测血清免疫球蛋白A1的含量,同时研究此类因子与紫癜性肾炎是否存在一定的相关性。3组结果对照,HSPN组和HSP组转化生长因子-β1、肿瘤坏死因子-α和免疫球蛋白A1水平均高于对照组,差异具有显著意义(p0.05);HSPN组IL-21、TGF-β1、TNF-α和Ig A1水平均高于HSP组,差异具有显著意义p0.05)。HSP患儿血浆TGF-β1水平与TNF-α呈正相关(r=0.478,p0.05)。IL-21、TGF-β1、TNF-α和Ig A1可能参与HSP和HSPN的发病过程,HSP患儿TNF-α水平的升高可能和TGF-β1水平改变有关,了解这些因子在HSP发病和发展过程的作用可以更好地指导临床对过敏性紫癜肾脏合并症的发生率和预后判断。     

高敏C-反应蛋白在紫癜性肾炎患儿中的应用

目的：探讨血清高敏C-反应蛋白（hs-CRP）在儿童紫癜性肾炎（HSPN）临床分型与病理分级中的应用价值,为基层医院提供一个可评价HSPN患儿病情严重程度的实验室相关指标。方法：应用免疫比浊法检测210例HSPN患儿不同临床分型与病理分级中的血清hs-CRP的水平,并与住院的70例的正常儿童作对照组进行比较。采用Pearson秩相关分析得出HSPN患儿血清hs-CRP水平临床分型与及病理分级的关系。结果：HSPN患儿血清hs-CRP水平明显高于对照组（HSPN组6.4±3.5 mg/L,对照组0.7±0.1mg/L）,差异有统计学意义（t=1.021,P=0.003）。HSPN患儿的血清hs-CRP水平与其临床分型的严重程度存在正相关（r=0.913,P〈0.05）。而HSPN患儿血清hs-CRP水平与其病理分级的关系也呈正相关（r=0.901,P〈0.05）。结论：随着HSPN患儿临床分型与病理分级的增高,其血清hs-CRP水平显著升高,HSPN患儿血清hs-CRP水平与其临床分型和病理分级之间均呈显著正相关,检测HSPN患儿血清hs-CRP水平可预测其临床分型和病理分级的程度,即HSPN患儿血清hs-CRP水平越高提示其临床分型和病理分级越重,因此检测HSPN患儿血清hs-CRP水平有助于评估HSPN患儿的病情、治疗效果和预后情况。     

紫癜性肾炎患儿血清Gd-IgA1、sFlt-1、IgA/C3比值与肾损伤和疗效的关系研究

摘要 目的：探讨紫癜性肾炎（HSPN）患儿血清半乳糖缺陷免疫球蛋白A1（Gd-IgA1）、可溶性fms-样酪氨酸激酶受体l（sFlt-1）、免疫球蛋白A（IgA）/补体C3（C3）比值与肾损伤和疗效的关系。方法：选取成都大学附属医院2019年12月至2021年12月确诊为HSPN的151例患儿作为病例组。另选取同期体检健康的志愿儿童100例作为对照组。对比两组血清Gd-IgA1、sFlt-1、IgA/C3比值、肾功能指标[尿素氮（BUN）、血肌酐（Scr）、24 h尿蛋白（UP）定量（24hUPE）和UP/Scr]。采用Pearson法分析血清Gd-IgA1、sFlt-1、IgA/C3比值与肾功能指标的相关性。对比不同肾脏病理分级和不同疗效患儿的血清Gd-IgA1、sFlt-1、IgA/C3比值。结果：病例组的Gd-IgA1、sFlt-1、IgA/C3比值、BUN、Scr、24hUPE、UP/Scr均高于对照组（P<0.05）。Pearson相关性分析结果显示：Gd-IgA1、sFlt-1、IgA/C3比值与BUN、Scr、24hUPE、UP/Scr均呈正相关（P<0.05）。随着肾脏病理分级的升高，HSPN患儿的血清Gd-IgA1、sFlt-1、IgA/C3比值不断升高（P<0.05）。无效组的Gd-IgA1、sFlt-1、IgA/C3比值高于有效组（P<0.05）。结论：Gd-IgA1、sFlt-1、IgA/C3比值升高参与了HSPN患儿的疾病进展，可导致肾损伤，加重肾脏病理改变，临床可根据上述指标变化指导治疗。     

血清Ghrelin、p21 waf/cip1以及IGF-1与儿童特发性矮小症相关性分析

摘要 目的：研究特发性矮小症（ISS）儿童血清生长激素释放肽（Ghrelin）、p21 waf/cip1以及胰岛素生长因子-1（IGF-1）水平及其临床意义。方法：选择2017年1月到2020年12月在我院接受治疗的特发性矮小症儿童60例（ISS组）,选择同期体检健康儿童60例作为对照（对照组）,比较两组儿童一般资料,检测并比较两组儿童血清Ghrelin、p21 waf/cip1以及IGF-1水平。分析ISS儿童血清Ghrelin、p21 waf/cip1以及IGF-1水平与生长指标的相关性,同时分析治疗对其影响。结果：（1）ISS组患儿性别、年龄和体质指数与对照组比较无显著差异（P>0.05）,但身高、体重以及生长速度显著低于对照组儿童（P<0.05）;（2）ISS组患儿血清Ghrelin和p21 waf/cip1均显著高于对照组,而血清IGF-1显著低于对照组（P<0.05）;（3）ISS组患儿血清Ghrelin和p21 waf/cip1均与身高、体重和生长速度呈负相关,而血清IGF-1与身高、体重和生长速度呈正相关（P<0.05）;（4）治疗显著提高ISS组患儿身高、体重、生长速度以及血清IGF-1水平,而显著降低ISS组患儿血清Ghrelin和p21 waf/cip1水平（P<0.05）。结论：Ghrelin、p21 waf/cip1和IGF-1在特发性矮小症患儿血清中表达异常,共同调控儿童生长发育,是评价儿童生长发育的良好指标。     

过敏性紫癜并肺炎支原体感染患儿免疫球蛋白和补体的研究

【摘 要】 目的 检测过敏性紫癜（HSP）合并肺炎支原体(MP) 感染的患儿血清免疫球蛋白及补体的水平,探讨MP感染与HSP的体液免疫学关系。方法 研究对象为55例HSP患儿,检测MP-IgM抗体,分为MP-IgM阳性组20例、MP-IgM阴性组35例,并以20名正常儿童作为对照组。采用全自动生化分析仪检测血清免疫球蛋白IgA、IgM、IgG、IgE及补体C3、C4。结果 HSP患儿MP感染阳性率达36.36%,合并MP感染的患儿临床症状更严重。与正常对照组相比,MP-IgM阴性组IgA、IgE明显增高（P<0.01）,C3水平降低（P<0.05）,同时IgE明显高于MP-IgM阳性组（P<0.01）,IgG、IgM、C4无明显变化。MP-IgM阳性组与正常对照组相比,IgA增高,IgM、C3、C4水平降低,且其中IgM、C3低于MP-IgM阴性组,差异均有统计学意义（P<0.05）,而IgG、IgE水平无明显改变。结论 在HSP儿童中有较高MP感染率,所有HSP患儿存在血清IgA增高及C3水平降低,说明体液免疫参与HSP的发病。伴MP感染的HSP患儿体液免疫功能更加紊乱,表现在C4水平下降,IgM、C3明显低于MP-IgM阴性组,IgE增高仅见于MP-IgM阴性组,提示MP感染的HSP患儿可能更多伴有低补体血症的自身免疫紊乱参与,说明MP感染引起的免疫紊乱可能在HSP发生、发展中具有重要作用。     

血清cTnI、CK-MB及IGF-1在新生儿高胆红素血症中的变化及临床意义

摘要 目的：分析血清肌钙蛋白T( troponin T,cTnT)、肌酸激酶同工酶(creatine kinase isoenzyme,CK-MB)及胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)在新生儿高胆红素血症中变化及临床价值。方法：选择2015年1月至2019年12月我院新生儿科收治的80例新生儿高胆红素血症足月新生儿(观察组)以及80例非胆红素足月新生儿(对照组)为研究对象。收集住院资料,包括所有患儿的胎龄、日龄、出生体重、血清总胆红素（total bilirubin,TBIL）、CK-MB、cTnT、IGF-1、头颅核磁共振(skull magnetic resonance,MRI)、临床表现等及出院后随访资料。根据胆红素水平高低,将观察组分为轻度(33例)、中度组(27例)及重度组(20例),比较其：TBIL、IGF-1、CK-MB、cTnT水平。结果：各组新生儿TBIL、CK-MB、cTnT水平比较差异具有统计学意义(P＜0.05)。重度黄疸组TBIL、CK-MB、cTnT值分别高于轻度、中度黄疸组和对照组,IGF-1低于轻度、中度黄疸组和对照组(P＜0.05);中度黄疸组TBIL、CK-MB、cTnT高于轻度黄疸组和对照组,IGF-1低于轻度黄疸组和对照组(P＜0.05);轻度黄疸组TBIL、CK-MB、cTnT高于对照组,IGF-1低于对照组(P＜0.05)。血清cTnT与TBIL水平呈正相关(r=0.587,P＜0.05);血清CK-MB与TBIL水平无明显相关性(r=0.220,P＞0.05);血清IGF-1与TBIL水平呈负相关（r=-0.568,P＜0.05）。苍白球异常信号组患儿血清IGF-1值为(11.05±0.51) ng/mL,明显低于苍白球正常信号组(14.22±2.67) ng/mL(P＜0.05);苍白球异常信号组患儿血清TBIL水平为(347.62±33.01)μmol/L与苍白球正常信号组(341.75±35.14)μmol/L无明显差别(P＞0.05)。结论：检测血清cTnT和IGF-1水平分别有助于预测新生儿高胆红素血症心肌损伤和脑病的发生。     

单核细胞趋化蛋白-1、可溶性血管细胞黏附分子-1与小儿紫癜性肾炎及其并发肾损伤的关系研究

摘要 目的：分析单核细胞趋化蛋白-1（MCP-1）、可溶性血管细胞黏附分子-1（sVCAM-1）与小儿紫癜性肾炎及其并发肾损伤的关系。方法：选择我院在2018年1月至2020年12月期间收治的108例紫癜性肾炎患儿作为观察组,另选108例健康体检儿童作为对照组。检测两组血清MCP-1、sVCAM-1表达水平,分析紫癜性肾炎患儿血清MCP-1、sVCAM-1表达水平与肾功能指标的关系,通过受试者工作特征曲线（ROC）下面积（AUC）评价血清MCP-1联合sVCAM-1判断肾损伤的效能。结果：观察组血清MCP-1、sVCAM-1表达水平均高于对照组（P＜0.05）;观察组24 h尿蛋白定量（24 h Upro）、胱抑素C（Cys-C）、血肌酐（SCr）表达水平均高于对照组（P＜0.05）;经Pearson相关性分析,紫癜性肾炎患儿血清MCP-1、sVCAM-1表达水平均与24 h Upro、Cys-C、SCr表达水平呈正相关（P＜0.05）;在108例紫癜性肾炎患儿中,发生肾损伤34例;肾损伤组血清MCP-1、sVCAM-1表达水平均高于非肾损伤组（P＜0.05）;经ROC曲线分析,血清MCP-1联合sVCAM-1判断紫癜性肾炎患儿发生肾损伤的AUC为0.862,明显大于单一指标MCP-1的0.660和sVCAM-1的0.663（P＜0.05）。结论：紫癜性肾炎患儿血清MCP-1、sVCAM-1表达水平升高,与肾脏受累程度有关,联合判断肾损伤的效能较好,为监测病情演变提供了新的参考依据,值得临床予以重视。     

过敏性紫癜患者银杏达莫注射液治疗前后血管内皮功能、凝血功能的变化及相关性研究

摘要 目的：探讨过敏性紫癜（HSP）患者银杏达莫注射液治疗前后血管内皮功能、凝血功能的变化,并分析HSP患者血管内皮功能与凝血功能的相关性。方法：选择2018年2月至2020年2月期间我院收治的HSP患者93例,按照随机数字表法将患者分为对照组（n=46）和观察组（n=47）,其中对照组给予糖皮质激素治疗,观察组给予银杏达莫注射液治疗,对比两组疗效、血管内皮功能、凝血功能的变化及紫癜性肾炎的发生率,并分析HSP患者血管内皮功能与凝血功能的相关性。结果：观察组治疗2周后的总有效率95.74%（45/47）,较对照组的76.09%（35/46）升高（P<0.05）。两组患者治疗2周后血清血管内皮生长因子（VEGF）、内皮素-1（ET-1）水平均降低,且观察组低于对照组（P<0.05）。两组患者治疗2周后纤维蛋白原（FIB）、D-二聚体（D-D）、血小板计数（PLT）均降低,且观察组低于对照组（P<0.05）,凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）均升高,且观察组高于对照组（P<0.05）。两组紫癜性肾炎发生率对比无统计学差异（P>0.05）。观察组患者中VEGF、ET-1均与FIB、D-D、PLT呈正相关,而与PT、APPT、TT呈负相关（P<0.05）。结论：HSP的发病过程中存在血管内皮细胞损伤及血液高凝状态,采用银杏达莫注射液治疗HSP患者,疗效显著,可有效改善患者血管内皮功能、凝血功能,且血管内皮功能与凝血功能存在一定的相关性。     

过敏性紫癜患儿血浆白细胞介素9水平变化及意义探讨

目的:探讨儿童过敏性紫癜急性期血浆白细胞介素9(IL-9)水平变化特点及其临床意义。方法:观察组为79例过敏性紫癜(HSP)患儿,分为无肾损害组和有肾损害两组;对照组为28例门诊健康体检儿童。ELISA测定各组儿童血浆IL-9及白细胞介素4(IL-4)水平。结果:HSP患儿血浆IL-9水平为(28.32±6.97)pg/ml,显著高于对照组(23.92±5.91)pg/ml,差异有统计学意义(t=2.98,p0.05);HSP患儿血浆IL-4水平为(93.86±25.35)pg/ml,显著高于对照组(77.75±15.90)pg/ml,差异有统计学意义(t=3.01,p0.05);紫癜有肾损害组及紫癜无肾损害组血清IL-4及IL-9水平较对照组明显升高,差异有统计学意义,p0.05。紫癜有肾损害组血清IL-9水平较紫癜无肾损害组明显升高,差异有统计学意义,p0.05。紫癜有肾损害组血清IL-4水平较紫癜无肾损害组升高不明显,差异无统计学意义,p0.05。直线相关分析结果显示,HSP患儿血浆IL-9水平变化与IL-4水平呈显著正相关(r=0.298,p0.05)。结论:IL-9水平的显著增高在HSP特别是紫癜性肾炎发病机制中有重要作用。     

缺氧诱导因子1α、血管内皮生长因子和成纤维细胞生长因子在胰腺癌中的表达及意义

目的：研究胰腺癌组织中缺氧诱导因子1alpha（Hypoxia-inducible factor-1alpha,HIF-1α）、血管内皮生长因子（vascular endothelial growth factor,VEGF）和成纤维细胞生长因子（fibroblast growth factor,FGF）的表达并探讨其意义。方法：Western blot法检测22例胰腺癌及癌旁组织中HIF-1α、VEGF和FGF蛋白的表达,分析HIF-1α与VEGF、FGF之间的相关性以及与性别、年龄、肿瘤大小、淋巴结转移和TNM分期之间的关系。结果：HIF-1α、VEGF和FGF在胰腺癌组织中的蛋白表达水平明显高于胰腺癌周组织（P〈0.01）,HIF-1α与VEGF、FGF之间的表达具有显著相关性（P〈0.01）。HIF-1α的表达与胰腺癌的TNM分期、肿瘤大小和淋巴结转移有关（P〈0.01）,VEGF和FGF的表达与胰腺癌的肿瘤大小和淋巴结转移有关（P〈0.05）。结论：HIF-1α可以上调VEGF和FGF的表达,在胰腺癌的发生、发展中起着重要作用。     

Acute Regulation of the Epidermal Growth Factor Receptor in Response to Nerve Growth Factor

PC12 cells possess specific receptors for both nerve growth factor and epidermal growth factor, and by an unknown mechanism, nerve growth factor is able to attenuate the propagation of a mitogenic response to epidermal growth factor. The differentiation response of PC12 cells to nerve growth factor, therefore, predominates over the proliferative response to epidermal growth factor. We have observed that the addition of nerve growth factor to PC12 cells rapidly produces a decrease in surface 125I-epidermal growth factor binding capacity. Unlike previously described nerve growth factor effects on 125I-epidermal growth factor binding capacity, which required several days of nerve growth factor exposure, the decreases we report occur within minutes of nerve growth factor addition: A 50% decrease in 125I-epidermal growth factor binding capacity is evident at 10 min. This rapid nerve growth factor response is concentration dependent; inhibition of 125I-epidermal growth factor binding is detectable at nerve growth factor levels as low as 0.2 ng/ml and is maximal at approximately 50 ng/ml, consistent with known ranges of biological activity. No demonstrable differences in the rate of epidermal growth factor receptor synthesis or degradation were observed in cells acutely exposed to nerve growth factor. Scatchard analysis revealed that acute nerve growth factor treatment decreased the number of both high- and low-affinity 125I-epidermal growth factor binding sites, while the receptor affinity remained unchanged. We have also investigated the involvement of various potential intracellular mediators of nerve growth factor action and of known intracellular modulatory systems of the epidermal growth factor receptor for their capacity to participate in this nerve growth factor activity.     

生长激素/胰岛素样生长因子1与阿尔茨海默病

生长激素／胰岛素样生长因子-1（GH／IGF-1）轴的合成、分泌、调节及生物学活性与阿尔茨海默病（AD）有密切关系。生长激素（GH）的合成和分泌受生长激素释放激素（GHRH）正向调节。GH／IGF-1轴活性下降导致一系列生理功能变化。GH／IGF-1缺乏可引起衰老及神经退行性变（AD）而导致认知功能的下降,相应激素的补给可以抑制或逆转这种认知障碍。越来越多的证据表明：GH／IGF-1参与AD型痴呆病理过程,对AD有很好的治疗应用前景。本文就生长激素／胰岛素样生长因子1在AD发病中的机理和药理学研究做一综述。     

Regulation by Interleukin-1 of Nerve Growth Factor Secretion and Nerve Growth Factor mRNA Expression in Rat Primary Astroglial Cultures

Primary cultures of neonatal rat cortical astrocytes contain low cellular levels (about 2 pg/mg of protein) of nerve growth factor (NGF), but secrete significant amounts of NGF into the culture medium (about 540 pg of NGF/mg of cell protein/38-h incubation). Incubation of astrocytes with interleukin-1 (IL-1) increased the cellular content of NGF and the amount secreted by about threefold. In comparison, cerebellar astrocytes secreted significant amounts of NGF, and the secretion was also stimulated by IL-1. The stimulatory action of IL-1 on astrocytes prepared from cortex was dose- and time-dependent. Concentrations of IL-1 causing half-maximal and maximal stimulation of NGF secretion were 1 and 10 U/ml, respectively). Maximal NGF secretion induced by IL-1 (10 U/ml) was seen following 38 h of incubation. The basal secretion of NGF was reduced by about 50% under Ca2(+)-free conditions; however, the percent stimulation of NGF secretion by IL-1 was the same in the absence or presence of Ca2+. The stimulatory action of IL-1 was specific, because other glial growth factors and cytokines were almost ineffective in stimulating NGF secretion from cortical astroglial cells. IL-1 treatment also increased cellular NGF mRNA content twofold. The results indicate that IL-1 specifically triggers a cascade of events, independent of cell growth, which regulate NGF mRNA content and NGF secretion by astrocytes.     

How IGF-II Binds to the Human Type 1 Insulin-like Growth Factor Receptor

1. Download : Download high-res image (216KB)
2. Download : Download full-size image

     

Insulin-Like Growth Factor I Receptor Expression and Function in Nerve Growth Factor-Differentiated PC12 Cells

Abstract: Receptors for insulin-like growth factor I (IGF-I) were studied on PC12EY cells, a subclone of PC12. Differentiation of PC12EY cells with nerve growth factor (NGF) did not alter either the number of IGF-I receptors nor their affinity for IGF-I. IGF-I receptors remained fully functional during differentiation, promoting increases in thymidine incorporation, glucose uptake, amino acid uptake, and the phosphorylation of the S6 protein of the ribosomes. IGF-I also increased the proportion of differentiated cells found in S-phase. But although the addition of IGF-I to naive cells caused an increase in cell number, there was no comparable increase when IGF-I was added to differentiated cells. Thus, although the receptor for IGF-I continues to be present and functional, IGF-I fails to induce cell proliferation in differentiated PC12 cells.     

GM1 Ganglioside Activates the High-Affinity Nerve Growth Factor Receptor trkA

Abstract: The monosialoganglioside GM1 has been shown to possess neurotrophic activity in vitro and in vivo and is now used as an experimental treatment for a variety of neurological disorders and trauma. Little is known about the mechanism of action used by GM1. Because GM1 appears to enhance nerve growth factor (NGF) activity, we have used C6trk⁺ cells, a derivative of C6-2B glioma cells that express the high-affinity receptor for NGF trkA , to determine whether the neurotrophic effects of GM1 occurs through induction of trkA activity. Exposure of C6trk⁺ cells to NGF (10–50 ng/ml) resulted in a five- to 10-fold increase in trkA tyrosine phosphorylation within 5 min. Incubation of cells with GM1 resulted in a threefold increase in trkA phosphorylation beginning within 1 h and peaking between 3 and 6 h. Optimal responses to GM1 were obtained using 80–100 µ M concentrations. Moreover, tyrosine phosphorylation of known trkA target proteins, such as extracellular signal-regulated kinases, and suc -associated neurotrophic factor-induced tyrosine-phosphorylated target, were activated upon stimulation of C6trk⁺ cells with GM1. In addition, GM1 potentiated the NGF-mediated activation of tyrosine phosphorylation of trkA . GM1 failed to induce phosphorylation of trkA and target proteins in mock transfected cells. Thus, our data demonstrate that GM1 mimics some of the effects of NGF and suggest that the neurotrophic properties of GM1 may be attributed to its activation of trkA signal transduction.     

肽类生长因子对抗癌基因的诱导作用

观察了肽类生长因子对２ＢＳ细胞中抗癌基因表达的影响。结果表明,ＥＧＦ或ＦＧＦ均可明显诱导２ＢＳ细胞中Ｒｂ基因的表达,其幅度分别为３０５％、２４３％;ＥＧＦ也可诱导２ＢＳ细胞中ＴＧＦβ１基因表达增加３０－５０％,但ＦＧＦ对ＴＧＦβ１的表达无明显影响;ＥＧＦ或ＦＧＦ对ｐ５３基因的表达均无明显诱导作用。上述结果为生长因子作用机制研究及生长因子与抗癌基因的关系提供了新的线索。     

杀伤血管内皮生长因子受体 1 阳性细胞的靶向毒素

白喉毒素 (diphtheria toxin DT) 是棒状白喉杆菌被β噬菌体感染后分泌的一种外毒素. 它可以阻断真核细胞的蛋白质合成,杀死细胞. 血管内皮生长因子 (VEGF) 的 R82A, K84A, H86A 突变体可以和肿瘤血管上高表达的 VEGF 受体 1 (VEGFR-1) 特异性结合. 首先从白喉杆菌中提取基因组 DNA,扩增出白喉毒素 C 区、 T 区基因. 并运用点突变技术,制成 VEGF 的 R82A, K84A, H86A 突变体. 利用这个可以和肿瘤血管上特异性受体相结合的 VEGF 的突变体,代替白喉毒素上的受体结合区,制成了针对 VEGFR-1 的靶向融合毒素——— DT391-mVEGF. 以去除了受体结合区的 DT391 为阴性对照,细胞实验表明,融合毒素对 VEGFR-1 阳性的肿瘤细胞有特异性杀伤作用.