糖类物质受体的研究进展

关于糖类物质的研究近年来越来越引起人们的极大兴趣。糖类物质具有广泛的生物学活性,其免疫调节作用是实现其生物学活性的重要机制之一。糖类物质生物学活性的发挥,主要是通过与细胞上不同的糖类物质受体相互作用,再经一系列信号转导的过程而实现的。该文综述了糖类物质的受体以及糖与受体蛋白的相互作用特点。     

类风湿性关节炎可溶性细胞因子的临床实验分析

目的：分析三种可溶性细胞因子受体（sIL-2R,sIL-6R,sTNFRI）对类风湿性关节炎的影响。方法：用ELISA方法测定了21例类风湿性关节炎患者血清中三种可溶性细胞因子受体的含量,并与其他指标进行了对比分析。结果：21例类风湿性关节炎患者的sIL-2R、sIL－6R和sTNFRI的水平显著升高（P〈0．01）。结论：三种可溶性细胞因子受体与类风湿性关节炎具有密切的关系,可作为临床监控指标;且具有一定的临床意义。     

Synthesis and biodistribution studies of two novel radioiodinated areno‐annelated estra‐1,3,5(10),16‐tetraene‐3‐ols as promising estrogen receptor radioligands

Two novel radioiodinated areno‐annelated estra‐1,3,5(10),16‐tetraenes, [¹²⁵I]2‐iodo‐1′‐methoxybenzo[4′,3′:16,17]estra‐1,3,5(10),16‐tetraene‐3‐ol ( 2 ‐[ ¹²⁵ I ]‐ MEBE ) and [¹²⁵I]4‐iodo‐1′‐methoxybenzo[4′,3′:16,17]estra‐1,3,5(10),16‐tetraene‐3‐ol, ( 4 ‐[ ¹²⁵ I ]‐ MEBE ) were synthesized for evaluation as potential ligands for the estrogen receptor. Radioiodination of 1′‐methoxybenzo[4′,3′:16,17]estra‐1,3,5(10),16‐tetraene‐3‐ol at the A ring was accomplished by electrophilic aromatic substitution using [¹²⁵I] sodium iodide and chloramine‐T as oxidant. After purification by reverse phase HPLC, the two radioisomers ( 2 ‐[ ¹²⁵ I ]‐ MEBE and 4 ‐[ ¹²⁵ I ]‐ MEBE ) were obtained in a radiochemical yield of 42 and 48%, respectively, in a radiochemical purity of greater than 95% and a high specific activity. The effect of the site of radioiodination (C₂ vs C₄) on the biological behaviour of the molecules was evaluated through biodistribution studies in immature female Sprague‐Dawley rats. Both 2 ‐[ ¹²⁵ I ]‐ MEBE and 4 ‐[ ¹²⁵ I ]‐ MEBE are stable in vivo and are mainly excreted through the hepatobiliary pathway. Both localize in the uterus and ovaries via a receptor‐mediated process, where the 2 ‐[ ¹²⁵ I ]‐ MEBE isomer has the higher specific ER binding and uterus selectivity. The favourable in vitro/in vivo stability and biodistribution profiles suggest that these radioligands are good candidates for further exploration of their potential clinical application. Copyright © 2006 John Wiley & Sons, Ltd.     

变应性鼻炎的药物治疗策略

变应性鼻炎(allergic rhinitis,AR)是耳鼻咽喉科常见的疾病,也是重要的变态反应性疾病之一.全球AR患者超过5亿,我国大陆地区AR的患病率为4％～38％[1].AR在给患者生活质量造成严重影响的同时,亦给社会带来沉重的经济负担[2].     

靶向联合阻断表皮生长因子受体和环氧化酶-2信号通路影响鼻咽癌细胞生长的研究

目的：观察联合阻断表皮生长因子受体（EGFR）和环氧化酶-2（COX-2）介导的信号通路,对鼻咽癌细胞株CNE-2的影响。方法：用EGFR-酪氨酸激酶拮抗剂和COX-2抑制剂单独和联合处理鼻咽癌细胞株CNE-2,采用CCK-8法检测细胞生长抑制率,流式细胞术进行细胞周期、凋亡率的分析,Western blot检测相关蛋白表达。结果：①联合用药组CNE-2细胞生长抑制率显著大于两者单独处理组生长抑制率之和（P〈0．05）;②联合处理组细胞G1期比例大于单独处理组（P〈0．05）。联合处理组细胞凋亡率与单独处理组相比差异无统计学意义（P〉0．05）;③与单独处理组相比,联合处理组出现明显的p—EGFR,COX-2表达下调。结论：联合阻断EGFR和COX-2信号通路对抑制鼻咽癌细胞株CNE-2生长,增加G1期阻滞及抑制EGFR的磷酸化和COX-2的表达方面具有协同作用。     

OSAHS患者综合治疗对血清sTNF—R工水平的影响

目的：了解OSAHS患者血清可溶性肿瘤坏死因子受体-I（sTNF-RI）的水平,评估0sAHs患者综合治疗对血清sTNF—RI水平的影响。方法：选择62例经多导睡眠监测仪诊断的OsAHS患者为实验组,15例非0SAHS患者为对照组。选取中重度组患者进行治疗前和治疗3个月后做前后对照比较,用酶联免疫吸附实验（ELISA）方法检测非OSAHS患者及OSAHS患者基础水平以及中重度组综合治疗前后血清sTNF—RI水平。结果：①实验组血清sTNF-RI水平（742±258pg／m1）较对照组（340±102pg／m1）明显升高（P〈O．05）;②中重度OSAHS治疗组患者血清sTNF-RI水平（351．4±116．9pg／m1）较治疗前（834．1±233．8pg／m1）明显降低（P〈0．05）;③控制体重、年龄、体质指数、性别等混杂因素后血清sTNF—RI水平与AHI呈正相关（r=0．646,P〈0．01）,与夜间最低氧饱和度呈负相关（r=0．522,P〈0．01）。结论：在控制体重、年龄、体质指数等混杂因素后,OSAHS患者严重程度与血清sTNF-RI有一定的相关性,综合治疗可以降低OSAHS患者血清sTNF-RI水平。     

131I治疗后Graves眼病血清TNF-α、sTNFRⅡ和sICAM-1的相关性研究

目的探讨G raves病眼病(GO)伴有甲状腺功能亢进症(甲亢)患者经131I治疗后,血清肿瘤坏死因子-α(TNF-α)、可溶性肿瘤坏死因子受体Ⅱ(sTNFRⅡ)和可溶性细胞间粘附分子-1(sICAM-1)的相关性。方法 131I治疗6～12个月间,根据"NOSPECS眼部病变分级"分为无GO组14例、轻度GO组35例和中度GO组35例,按"CAS评分"分为GO静止组32例和GO活动组38例。设对照组29例。采用ELISA方法检测各组患者血清sI-CAM-1、TNF-α和sTNFRⅡ水平。结果 GO活动组血清sICAM-1(1211.9±258.6ng/m l)水平高于对照组(697.8±291.0 ng/m l)、无GO组和GO静止组(797.6±250.0 ng/m l、807.9±330.2ng/m l,P<0.01),GO静止组和GO活动组血清TNF-α(378.1±167.9ng/L、391.6±150.7ng/L)水平均高于无GO组和对照组(P<0.01);无GO组、GO静止组和GO活动组血清sTNFRⅡ(730.0±173.3ng/L、1055.1±422.9 ng/L、960.0±435.4 ng/L)水平均高于对照组(P<0.01)。轻度GO组、中度GO组血清sICAM-1(1032.4±232.3 ng/m l、407.0±158.1 ng/L)和TNF-α(1021.9±448.9 ng/m l、375.2±157.8 ng/L)水平均高于无GO组和对照组(P<0.05);而无GO组、轻度GO组和中度GO组血清sTNFRⅡ(730.0±173.3 ng/m l、1154.4±422.9 ng/L、922.1±440.6 ng/L)水平均高于对照组(P<0.05)。全部患者血清sICAM-1分别与TNF-α、sTNFRⅡ呈正相关,(r=0.377,P=0.001,r=0.434,P=0.001),TNF-α和sTNFRⅡ之间呈正相关(r=0.476,P<0.001)。结论 GO患者131I治疗的早期,通过血清sICAM-1、TNF-α和sTNFRⅡ的表达对活动性突眼、眼眶内免疫炎性反应,纤维组织变化和甲亢缓解进行综合评价,并可结合CAS评分了解GO患者预后、甲状腺及眼眶的免疫学及细胞凋亡的状态,指导有针对性治疗。     

N-甲基-D-天门冬氨酸受体亚型NR1、NR2A在大鼠视网膜缺血再灌注损伤模型中的表达

目的:研究N-甲基-D-天门冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR)功能亚单位NMDAR1、NM-DAR2A在Wister大鼠视网膜缺血再灌注模型中的表达情况。方法:18只健康成年Wister大鼠分成6组,每组3只,都取其右眼行视神经周围血管结扎手术制备视网膜缺血再灌注模型,左眼作为对照组不行手术。60分钟后去除结扎缝线恢复血流,分别于再灌注后即刻、3、12、24、72、168小时处死大鼠,摘除眼球,做冰冻切片。用免疫组织化学方法观察NR1、NR2A在视网膜缺血再灌注后不同时刻的变化并进行图象分析及统计学处理。结果:(1)各实验组和对照组间及各实验组间NMDAR1的表达无统计学意义。(2)除即刻组外各实验组和对照组间及各实验组间NMDAR2A的表达均有统计学意义,从再灌注后3小时至168小时NMDR2A表达缓慢上升。结论:(1)NMDAR1与视网膜缺血再灌注损伤无关,不参与谷氨酸的兴奋性毒性作用。(2)NMDAR2A与视网膜缺血再灌注损伤有关,参与谷氨酸兴奋性毒性作用。     

Diagnostic and management challenges from childhood,puberty through to transition in severe insulin resistance due to insulin receptor mutations

Two Caucasian girls, both of normal weight and body mass indices, were diagnosed with type A insulin resistance (IR) in childhood. Case 1 presented with premature adrenarche aged 7 years, then by age 12 years had hirsutism, acne, acanthosis nigricans, and asymptomatic diabetes. Subsequent investigation revealed raised adiponectin (15.3 mg/L) and heterozygous p.Pro1205Leu mutation in the INSR gene encoding the insulin receptor. She experienced postprandial hypoglycaemia on metformin; acarbose was trialled and discontinued aged 16 years, as she became normoglycaemic. Hirsutism was treated with topical eflornithine, oral spironolactone and flutamide, and laser therapy. Unfortunately, diabetes reemerged in young adulthood with obesity. Case 2: during an emergency admission for acute abdominal pain aged 11 years, hyperglycaemia was noted which led to further investigation. An oral glucose tolerance test showed diabetes and ultrasound showed polycystic ovaries. Further investigations revealed raised adiponectin (18 mg/L) and compound heterozygous mutations in the INSR gene: p.Pro1263Ala and p.Ser748Leu (latter probable normal variant). She was treated with metformin and experienced postprandial hypoglycaemia. Symptoms of hyperandrogenism were controlled by flutamide. She maintained a healthy weight and reassessment at young adulthood showed resolution of diabetes. Type A IR may present in childhood with overlapping features of common endocrine entities such as premature adrenarche and polycystic ovarian syndrome. Patients with abnormal glucose tolerance yet normal weight merit screening with adiponectin; raised adiponectin levels prompt insulin receptor mutational analysis. Postprandial hypoglycaemia is characteristic. Management includes optimization of glycaemic control with oral hypoglycaemic agents and maintenance of healthy weight, and controlling the effects of hyperandrogenism.     

γ-氨基丁酸受体γ1亚基在大鼠前庭终器的表达

目的：研究γ-氨基丁酸受体γ1亚基在大鼠前庭终器的表达。方法；运用RT-PCR技术检测大鼠前庭终器编码GABAA受体亚基因表达。以大鼠脑组织RNA为阳性对照。结果：扩增出标志GABAA受体基因表达的PCR产物。结论:GABA受体γ1亚基在大鼠前庭终器有表达，为证明GABA是前庭系统重要神经递质之一提供了支持。