血管内皮生长因子在肾病大鼠中的表达及意义

目的:探讨血管内皮生长因子(VEGF)在阿霉素肾病大鼠中的表达及意义。方法:雄性Wistar大鼠62只,随机分为正常对照组、肾病综合征组(NS)。于7d、14d、28d检测血、尿、肾组织VEGF的含量。结果:N S组VEGF在血、尿、肾组织中的含量均显著高于正常对照组(P<0.01),且均与24h尿蛋白量呈正相关(r=0.775;0.807;0.629;P<0.01)。结论:阿霉素肾病大鼠血、尿、肾组织VEGF的表达与24h尿蛋白量呈正相关,提示VEGF参与了阿霉素肾病大鼠蛋白尿的发生。     

细胞间黏附分子-1在多柔比星肾病大鼠中的表达及意义

目的:观察细胞间黏附分子-1( intercellular adhesion molecule-1,ICAM-1)在多柔比星肾病大鼠肾组织中的表达,探讨 ICAM-1在微小病变肾病综合征(MCNS)尤其是蛋白尿中的作用机制.方法:雄性Wistar大鼠85只随机分为正常组(40只)、肾病组(45只).肾病组单次尾静脉注射多柔比星5mg/kg,建立MCNS模型,正常组注射等量生理盐水.于造模后第7d、14d、28d、42d测定各组大鼠24 h尿蛋白、血清白蛋白、胆固醇、甘油三酯、肌酐及尿素氮含量,同时采用免疫组织化学染色检测肾组织中ICAM-1的表达.结果:①肾病组大鼠尿蛋白排泄量逐渐增加,且各时期与正常组比较明显升高,均有显著性差异(P＜0.01) ;②肾病组大鼠肾组织中ICAM-1表达较正常组明显增加,有显著性差异(P＜0.01);③肾病组肾组织中ICAM-1的表达与24h尿蛋白的排泄量呈正相关(r=0.919,P<0.01).结论:ICAM-1在MCNS肾组织中表达明显增多,它的异常表达与蛋白尿的发生密切相关.     

血管紧张素Ⅱ-1型受体拮抗剂对阿霉素肾病大鼠干预效果的实验研究

目的 探讨血管紧张素Ⅱ-1受体拮抗剂(AT1RA)缬沙坦对大鼠肾病综合征病理及相关临床指标的干预作用及可能机制。方法 采用阿霉素肾病(AN)模型，将大鼠分为阿霉素肾病组和缬沙坦及苯拉普利治疗组，检测大鼠24h尿蛋白排泄量、血肌酐、尿素氮及其他生化指标，并取肾脏进行光镜及电镜检查，放射免疫分析法测定血浆及肾组织血管紧张素Ⅱ含量，并没正常对照组。结果 缬沙坦及苯拉普利可降低阿霉素肾病大鼠的蛋白尿排泄，改善生化指标。结论 缬沙坦对阿霉素肾病大鼠的肾脏具有保护效应，减轻肾损伤，降低蛋白尿。     

外周血高迁移率族蛋白-1和NF-κB在肾病综合征中的作用

目的分析原发性肾病综合征患者血清中HMGB-1、NF-κB的关系,探讨其在原发性肾病综合征中的作用。方法2014年1月至2015年7月我院40例原发性肾病综合征患者为观察组,同时纳入40例健康体检者为对照组。采用ELISA法测定外周血清中HMGB-1、NF-κB的浓度,同时收集受试者尿蛋白、血脂等相关临床资料。评价尿蛋白定量、TG、TC、HDL-C、LDL-C水平、血清白蛋白水平、C-反应蛋白水平及血清HMGB-1、NF-κB水平。采用Pearson相关性分析进行变量之间的统计学分析。结果观察组HMGB-1和NF-κB的浓度均高于对照组,差异有统计学意义(P<0.01)。Pearson相关分析结果显示,HMGB-1与尿蛋白定量(r=0.74,P<0.01)、TG(r=0.33,P<0.01)、TC(r=0.52,P<0.01)、LDL-C(r=0.26,P<0.01)、CRP(r=0.41,P<0.01)呈正相关,与白蛋白(r=-0.56,P<0.01)呈负相关。NF-κB与尿蛋白定量(r=0.62,P<0.01)、TG(r=0.28,P<0.01)、TC(r=0.43,P<0.01)、LDL-C(r=0.29,P<0.01)呈正相关,与白蛋白(r=-0.45,P<0.01)呈负相关。HMGB-1与NF-κB呈正相关,相关系数为0.84,差异有统计学意义(P<0.01)。结论原发性肾病综合征患者血清中HMGB-1、NF-κB水平均升高,两者呈正相关。HMGB-1在肾病综合征的发病中可能通过NF-κB起作用。     

罗格列酮对阿霉素肾病大鼠足细胞nephrin表达的影响

目的建立阿霉素肾病模型,探讨罗格列酮对阿霉素肾病大鼠足细胞nephrin的表达的影响。方法21只大鼠随机分为3组。阿霉素肾病组和罗格列酮组大鼠予0.1%阿霉素溶液7 mg·kg~(-1)一次性尾静脉注射,罗格列酮组次日予罗格列酮5 mg·kg~(-1)·d~(-1)灌胃,每日1次,共8 wk。另外2组每日予等量自来水灌胃。检测各组大鼠24 h尿蛋白定量、血清清蛋白、血脂、肾功能及肾脏病理改变,并检测肾组织nephrin和TCFβ_1的表达。结果给药后2、4、6、8 wk,罗格列酮组大鼠24 h尿蛋白定量明显低于阿霉素肾病组(P<0.05),8 wk时其血清清蛋白高于阿霉素肾病组[(26.7±s 2.6)g·L~(-1)vs(21±4)g·L~(-1),P<0.05],血三酰甘油和胆固醇水平低于阿霉素肾病组(P<0.05)。与阿霉素肾病组比较,罗格列酮组大鼠肾组织中nephrin蛋白表达增高19%(P<0.05),而TGFβ_1蛋白表达明显降低(P<0.01),肾脏病理损害也明显减轻。结论罗格列酮可上调阿霉素肾病大鼠肾组织nephrin表达,减少尿蛋白排泄,抑制其TGFβ_1表达,从而减轻肾组织病理损害。     

1,25(OH)2D3对阿霉素肾病大鼠HGF表达的影响

目的:观察肝细胞生长因子(hepatocyte growth factor,HGF)在阿霉素肾病大鼠血液及肾组织中的表达,探讨1,25(OH)2D3对微小病变肾病综合征(MCNS)HGF表达的影响及其对微小病变肾病综合征的保护机制.方法:雄性Wistar大鼠110只随机分为正常组(32只)、肾病组(78只).肾病组单次尾静脉注射阿霉素5mg/kg,建立MCNS模型,正常组给予注射等量生理盐水.造模后第7天检测全部大鼠24h尿液中尿蛋白含量,尿蛋白＞30mg/24h者为MCNS造模成功.剔除5只,将造模成功的大鼠(共73只)再随机分为两组:肾病对照组(n=37),治疗组(n=36).于造模后第7d、14d、28d、42d测定各组大鼠24h尿蛋白、血清白蛋白、胆固醇含量,同时采用夹心ELISA方法检测各组大鼠血液、肾组织中HGF的水平.结果:与正常组比较对照组大鼠血液及肾组织中HGF表达有所增加(P＜0.01).治疗组HGF的表达水平较对照组显著升高(P＜0.01).而尿蛋白排泄量与对照组比较,则有明显降低(P＜0.01).结论:1,25(OH)2D3对于微小病变肾病综合征至少有部分保护作用,其机制可能为通过上调HGF的表达,从而对阿霉素肾病大鼠肾脏起保护作用.     

低分子肝素对肾病综合征大鼠血栓素A_2及前列环素表达的影响

目的探讨低分子肝素(LMWH)对肾病综合征(NS)大鼠肾脏保护作用的可能机制。方法将雄性SD大鼠随机分为正常对照组、肾病综合征模型组、肾病综合征模型加低分子肝素治疗组,分别于2、3、4周留取24 h尿,测定尿蛋白,并离心沉淀备测血栓素A2(TXA2)和前列环素(PGI2),同时腹主动脉取血测定血清白蛋白。结果肾病综合征大鼠尿中TXA2明显增加,随病变发展逐渐升高。而PGI2没有明显变化。LMWH治疗后尿中PGI2浓度升高,24 h尿蛋白减少,血清白蛋白升高。结论LMWH可增加NS大鼠尿中PGI2浓度,纠正TXA2/PGI2比值失衡,是其保护肾脏的可能机制之一。     

来氟米特对阿霉素肾病大鼠尿、肾脏VEGF表达的影响

目的:探讨来氟米特对阿霉素肾病大鼠尿、肾脏血管内皮生长因子(VEGF)表达的影响。方法:将56只清洁级雄性Wistar大鼠随机分为正常对照组(生理盐水组)、肾病组(阿霉素组)、治疗组(来氟米特组)。建立阿霉素肾病大鼠模型,各组分别于第2周、4周、6周处死大鼠,取尿、肾脏,用ELISA方法检测并做相关分析。结果:肾病组在第2周、4周、6周时VEGF在尿、肾组织中的含量均显著高于正常对照组(P<0.01);且均与24h尿蛋白量呈正相关(r=0.81;0.63;P<0.01);来氟米特(LEF)干预组上述指标均显著低于肾病组,差异有统计学意义(P<0.01)。结论:来氟米特对阿霉素肾病大鼠肾脏损害有保护作用,其机制可能是通过降低VEGF表达而实现。     

褪黑素对多柔比星所致肾病的保护作用

本研究旨在观察褪黑素 ( MT)对大鼠“阿霉素肾病”的保护作用 .将所有受试动物分为 5组 ,即正常组 ,MT( d0 - d7,5mg·kg-1·d-1,ig)组 ,多柔比星模型组 ( d 1 ,Dox,5mg· kg-1,iv)组和MT( d 0 - d 7,0 .5,5mg· kg-1· d-1) + Dox( d 1 ,5mg· kg-1,iv)组 .检测大鼠 d7,d1 4,d2 1和 d2 8时尿蛋白 ,尿丙二醛排泄量和 d 2 8时血浆生化指标 .结果显示 ,Dox组大鼠呈典型的肾病综合征 ,MT+ Dox组大鼠尿蛋白减少 ,血浆蛋白明显回升 ,血脂降低 ;同时 ,Dox组动物尿丙二醛显著增加 ,MT+ Dox组丙二醛降低 .这些结果表明 ,MT可减轻“阿霉素肾病”大鼠肾损害 .     

贝那普利、螺内酯联用对阿霉素肾病大鼠肾小管保护作用的研究

目的:观察贝那普利、螺内酯联合应用于阿霉素肾病大鼠降低蛋白尿及增加的肾小管保护作用。方法:42只SD大鼠随机抽取7只为正常对照组,余下经尾静脉注射阿霉素制备肾病模型。6周后29只造模成功的大鼠(24h尿蛋白>100mg)随机分为:模型组(n=7),贝那普利组(n=8),螺内酯组(n=7),贝那普利和螺内酯联合治疗组(联合用药组,n=7)。分别于6、12、18周末收集24h尿液,检测24h尿蛋白,并于18周末测尿视黄醛结合蛋白(RBP)后,处死大鼠经腹主动脉取血液标本检测生化指标。取出肾组织HE染色,并采用免疫组织化学方法检测肾小管间质转化生长因子-β1(TGF-β1)的表达。结果:各治疗组均能显著降低阿霉素肾病大鼠血压、蛋白尿,升高血清白蛋白(P<0.05),其中贝那普利组和联合治疗组疗效优于螺内酯组,以联合治疗组疗效最为显著;与模型组比较各治疗组尿RBP水平均下降(P<0.01),其中联合治疗组疗效优于单独治疗组(P<0.01)。联合治疗组抑制TGF-β1的表达优于治疗组和模型组。治疗组尿RBP和TGF-β1均表现为强相关(r=0.735、r=0.845、r=0.585)。结论:在阿霉素大鼠模型中,贝那普利和螺内酯联合应用能降低蛋白尿,抑制TGF-β1合成,减轻肾小管损伤。     

Growth hormone secretagogues

Growth hormone secretagogues (GHSs) are synthetically produced peptides and non-peptides that stimulate growth hormone (GH) release by acting on one or more specific receptors. Treatment with GH itself is established in GH deficient children and adults and may also be useful in frail, elderly adults, in abdominally/viscerally obese subjects, in patients with congestive heart failure and in patients suffering from nitrogen-wasting catabolic disease. In these conditions, the newly developed class of orally-active GHSs may be attractive alternatives to sc. GH injections. This review focuses on recently patented GHSs and their claimed indications, however, other GHSs and their possible uses have also been included.     

Effects of anthralin and hypericin on growth factor signalling and cell proliferation in vitro

The effect of the anthranoids, anthralin and hypericin, on epidermal growth factor receptor (EGF-R) activation and their degree of specificity was examined. Hypericin, but not anthralin, was found to inhibit binding of [¹²⁵I]-labelled epidermal growth factor (EGF) to HN5 squamous carcinoma cells that overexpress EGF-R. This effect was a result of a dose- and time-dependent reduction of EGF-R number and affinity. Neither compound directly inhibited EGF-induced tyrosine phosphorylation of the EGF-R in HN5 cells. Although anthralin and hypericin both inhibited the mitogenic effect of EGF in NR6/HER cells (IC₅₀s = 100 nM and 10 μM, respectively), they also had comparable effects on DNA synthesis in response to acidic fibroblast growth factor (aFGF) and platelet-derived growth factor (PDGF). When tested in proliferation assays using cells expressing differing numbers of EGF-R, the growth inhibitory effects of both compounds were independent of EGF-R number. We conclude that, although anthralin and hypericin both inhibit EGF signalling, they do not act specifically on the EGF-R pathway. Moreover, their mechanisms of action do not appear to be comparable.     

Mapping the receptor-recognition site of human transforming growth factor-α

The receptor-recognition site human transforming growth factor-α (TGFα), a 50-residue tricyclic peptide with three disulfide bonds, was mapped by a set of 46 peptide analogs consisting of linear, monocyclic, bicyclic, and tricyclic structures representing individual and overlapping subdomains of human TGFα. Linear overlapping fragments ranging from 7 to 18 residues and spanning the entire length of TGFα as well as monocyclic analogs with one disulfide linkage were found to be inactive in both receptor-binding and mitogenic assays. Bicyclic analogs with two disulfide linkage and representing either the amino or carboxyl two-thirds of TGFα showed low activity at 0.1–0.9 mm concentrations. Tricyclic analogs containing all three disulfide linkages but lacking either the amino or carboxyl terminal heptapeptide was, respectively, 3% and 0.1 % as active as TGFα. These results show that determinants for the receptor binding cannot be represented by a short continuous fragment or a single subdomain, but are located on a discontinuous surface on a folded structure with disulfide restraints. Furthermore, these results when combined with our previous results which shows that the middle subdomain (second disulfide loop) is not involved in the receptor binding suggest that the receptor-binding residues are constituted of three fragments located at the first and third subdomains as well as the external carboxyl peptide.     

宫内发育迟缓儿与胰岛素样生长因子-1和胰岛素样生长因子结合蛋白-3关系的研究

目的研究宫内发育迟缓（IUGR）儿与胰岛素样生长因子-1（IGF-1）和胰岛素样生长因子结合蛋白-3（IGFBP-3）的关系。方法用放射免疫法测定该院及复旦大学附属妇产科医院确诊的宫内发育迟缓儿（92例）和同期正常出生体重儿（AGA）（32例）脐血IGF-1和IGFBP-3的水平。结果IUGR组IGF-1为（29．2±26．5）μg／L，IGFBP-3为（1364．7±703．5）μg／L，对照组分别为（61．1±56．4）μg／L、（2344．7±1573．3）μg／L，两组比较差异有统计学意义。结论IGF-1和IGFBP-3对胎儿的生长发育起着重要的调节作用。     

生长激素在肝纤维化患者中的应用

生长激素不但能在生长过程中起重要作用,而且在碳水化合物,脂类代谢过程中起重要作用。慢性肝病的一个重要特征是生长激素抵抗现象,其表现为血清中生长激素的浓度较高而胰岛素样生长因子-1的水平降低。使用生长激素治疗慢性肝病,可提高患者血清中胰岛素样生长因子-1和胰岛素样生长因子结合蛋白-3升高,改善患者的生长激素抵抗现象,改善肝功能,纠正低蛋白血症。该文就使用生长激素治疗慢性肝病和肝纤维化的研究现状做一简要综述。     

Nerve Growth Factor Suppresses Prostate Tumor Growth

Nerve growth factor (NGF) facilitates reinnervation of perivascular nerves that regulate vascular tone and blood flow. This study investigated whether NGF prevents tumor growth by promoting neuronal regulation of tumor blood flow. The growth rate of DU145 prostate carcinoma cells subcutaneously implanted into nude mice was significantly inhibited by subcutaneous NGF administration. Significant suppression of tumor growth continued after withdrawing NGF. NGF increased vascular smooth muscle cells in tumor tissues, but had no cytotoxic action on tumor cells in vitro. These results suggest that NGF prevents tumor growth via an indirect effect, probably innervation or maturation of the tumor neovasculature.     

An equine growth hormone molecular species lacking the 76-92 peptidic fragment

A new eGH molecular species was isolated and purified by reverse phase HPLC. SDS-polyacrylamide gel electrophoresis, amino acid composition, and C- and N-terminal determinations support a primary structure identical to that described by Zakin el al. (1976), except for the lack of the 76-92 peptidic fragment and the maintaining of 30% of its biological activity.