葛根素对糖尿病大鼠主动脉糖基化终产物的形成及其受体表达的影响

目的　观察葛根素 (Puerarin ,Pue)对糖尿病 (DM)大鼠主动脉糖基化终产物 (AGEs)的形成及其受体 (RAGEmRNA)表达的影响。方法　以STZ诱导DM大鼠模型 ,并将DM大鼠随机分为DM对照组 (DM)、不同剂量葛根素治疗组 (0 5、0 2 5、0 1 2 5g·kg-1 ,ig )和氨基胍治疗组 (0 1g·kg-1 ,ig) ,另设一正常对照组 ,给药 1 2wk后 ,分别以葡萄糖氧化酶法测定血糖 ,NBT法测定血清果糖胺的含量 ,采用荧光法、RT PCR方法分别对主动脉AGEs的沉积及RAGEmRNA的表达进行检测。结果　Pue治疗后DM大鼠血糖、血清果糖胺含量明显降低 ,主动脉AGEs的形成量也明显低于DM模型组 (P <0 0 1 ) ,其治疗作用与氨基胍 (AG)相当 ;RAGE主要在内皮细胞表达 ,其表达量与AGEs的沉积量呈明显正相关 ,而葛根素也可明显下调RAGEmRNA在DM大鼠主动脉中的表达 (P<0 0 1 )。结论　葛根素可通过有效降低糖尿病大鼠血糖、血清果糖胺的含量 ,减少主动脉AGEs的沉积 ,下调主动脉中RAGEmRNA的表达 ,即通过抑制糖尿病大鼠主动脉非酶糖化的形成来防治DM血管病变的发生发展     

葛根素对STZ诱导的糖尿病大鼠视网膜的保护作用及机制研究

目的探讨葛根素对糖尿病大鼠视网膜的保护作用及可能机制。方法 40只♂SD大鼠随机分为正常对照组、糖尿病(DM)模型组、DM+葛根素低剂量组(Pue1组)、DM+葛根素高剂量组(Pue2组)。给药后4周,行视网膜组织病理学检查,荧光法检测视网膜晚期糖基化终末产物(ad-vanced glycation end products,AGEs)含量、Real-time PCR法、Western blot法分别检测视网膜组织晚期糖基化终末产物受体(receptor of advanced glycation end products,RAGE)、血管内皮生长因子(vascular endothelial growth factor,VEGF)mR-NA表达和蛋白水平。结果 DM组视网膜外核层细胞厚度明显变薄,Pue2组较DM组有所好转。DM大鼠视网膜中VEGF的mRNA和蛋白表达水平均明显高于正常对照组(P<0.01);Pue1、Pue2组VEGF的mRNA和蛋白表达水平均明显下降(P<0.01)。DM大鼠视网膜内AGEs水平较正常对照组明显上调(P<0.05),高剂量葛根素能抑制AGEs形成(P<0.05)。RT-PCR与Western blot结果显示,DM大鼠视网膜中RAGE的mRNA水平和蛋白表达均高于正常对照组(P<0.05),高剂量葛根素可使之下调(P<0.05)。结论葛根素可抑制DM大鼠视网膜AGEs形成及RAGE的表达,抑制视网膜VEGF的表达,起到保护糖尿病大鼠视网膜的作用。     

加味五味消毒饮提取物对糖尿病大鼠牙周组织的保护作用

目的：观察加味五味消毒饮提取物（modi—fledwuweixiaoduyinextracts，MWE）对糖尿病（diabeticmellitus，DM）大鼠牙周组织的保护作用并探讨其初步机制。方法：以栓线法结合注射链脲佐菌素（streptozotocin，STZ，50mg／kg）法制备糖尿病性牙周炎动物模型。实验分5组，正常对照组、模型组、氨基胍（Aminoguanidine，AG）阳性组（100mg／kg）、MWE治疗小剂量组（20g生药／kg）和大剂量组（40g生药／kg），每组动物数10只。灌胃给药治疗6周后处死大鼠，测定空腹血糖值和糖化血红蛋白（GHb）水平，ELISA法测定血清晚期糖基化终产物（AGEs）浓度，牙周探针测量牙周袋深度，X光牙片机检查大鼠左上颌牙槽骨组织变化，免疫组化法检测牙龈组织AGEs受体（receptorforAGEs，RAGE）蛋白表达。结果：治疗6周后，MWE几乎没有降血糖作用，但与模型组相比，治疗组牙周袋深度下降，GHb和AGEs水平降低（P〈0．01），骨小粱排列紊乱状况和牙槽骨水平吸收有所改善，RAGE蛋白表达水平也有下降。结论：MwE对糖尿病大鼠牙周组织具有保护作用，其机制可能与干扰AGEs—RAGE信号通路有关。     

金钗石斛对糖尿病大鼠肾组织中糖基化终产物表达的干预作用

目的研究金钗石斛对糖尿病(DM)大鼠肾组织中肾脏糖基化终产物受体(RAGE)表达的干预作用。方法将W istar大鼠随机分3组,用链脲佐菌素(STZ)建立DM模型,金钗石斛水煎剂10 g/(kg.d)灌胃给药12周后,肾组织病理切片HE染色观察肾组织病理变化;生化法测定血糖、尿蛋白、肌酐浓度;荧光光谱法测定尿液和血清糖基化终产物(AGE)含量;免疫组化检测肾组织RAGE蛋白;实时荧光定量PCR检测肾组织RAGE mRNA表达。结果金钗石斛可降低DM模型大鼠血糖,减轻肾脏损害,降低血清中AGE以及肾组织RAGE mRNA和蛋白表达水平。结论金钗石斛干预减轻DM肾脏功能损害可能通过降低血清中AGE和下调肾组织中RAGE表达而实现。     

西红花酸对AGEs诱导血管内皮细胞通透性增加的抑制作用

目的研究西红花酸对晚期糖基化终产物(advancedglycation end products,AGEs)诱导血管内皮细胞通透性增加的抑制作用并探讨其机制。方法用不同剂量西红花酸(0.01、0.1、1μmol.L-1)预孵牛主动脉血管内皮细胞(bo-vine vascular endothelial cells,BECs)12 h后,AGEs(100μg.L-1)刺激内皮细胞,以HRP作示踪剂检测内皮细胞单层通透性变化,ELISA法测定细胞上清MCP-1和TNF-α水平,罗丹明-鬼笔环肽荧光染色检测细胞骨架蛋白F-actin变化,Cell-based ELISA法和液闪法分别测定磷酸化p38 MAPK蛋白表达量和活性变化。同时设定正常对照组(control)、AGEs(100 mg.L-1)模型组和葛根素(1 g.L-1)阳性对照组。结果与AGEs模型照组相比,西红花酸(0.1、1μmol.L-1)预孵细胞后,F-actin骨架蛋白破环程度有所减轻,细胞单层通透性减小(P<0.01或0.05),TNF-α和MCP-1分泌降低,磷酸化p38MAPK的数量下降且活性被抑制(P<0.01或0.05)。结论西红花酸对AGEs诱导内皮细胞通透性增加有抑制作用,该作用可能与其抑制p38MAPK通路有关,这可能是其抗糖尿病血管病变的机制之一。     

晚期糖基化终末产物及受体在实验性2型糖尿病大鼠种植体周围的变化及表达

目的建立2型糖尿病大鼠动物模型,探讨晚期糖基化终末产物及其受体在实验性2型糖尿病大鼠种植体骨整合过程中的变化及表达。方法 45只3个月龄SD健康雄性大鼠,将大鼠随机分为糖尿病模型组25只和正常对照组20只。首先建立2型糖尿病大鼠模型,建模成功后将模型大鼠随机分为DM组和DM种植组,每组10只。将20只正常组大鼠随机分为正常对照组和正常种植组,每组10只。分别于正常种植组和DM种植组的胫骨近骺端植入纯钛种植体,植入10周后于下腔静脉采血,保存所采集标本,用RF-5301PC型荧光分光光度计测定血清中AGEs含量的变化。硬组织标本采用不带种植体脱钙切片,以正常组为对照,HE染色后用免疫组织化学方法检测种植体周围RAGE的表达。结果 10周后,DM种植组和DM组与正常对照组和正常种植组相比,血清中AGEs的变化差异有统计学意义(P<0.05),正常种植组和DM种植组与正常对照组的种植体周围骨组织RAGE表达比较,差异均有统计学意义(P<0.05);DM种植组与DM组比较,差异亦有统计学意义(P<0.05)。结论种植体骨组织愈合过程中AGEs和RAGE相互作用是影响2型糖尿病种植体骨结合的机制之一。     

糖尿病大鼠甲状腺组织RAGE mRNA和蛋白表达的变化

目的:探讨糖尿病(DM)大鼠甲状腺组织终末糖基化产物受体(RAGE)mRNA和蛋白的表达水平及其与血糖的关系.方法:经高脂饲料喂养联合注射小剂量链脲佐菌素制备DM大鼠49只,随机分为DM组(17只)、胰岛素干预组(DI组,16只)、氨基胍干预组(DA组,16只),另设正常对照组(NC组,9只).成模12周末测空腹血糖后,经股动脉放血处死大鼠.取甲状腺组织,分别以GAPDH和β-actin作为内对照,用半定量RT-PCR和Western Blot方法测定各组RAGEmRNA和蛋白的表达.结果:DM组大鼠血糖为(31.72±9.29)mmol/L、甲状腺组织RAGE mRNA与GAPDHmRNA表达比为0.90±0.30,RAGE蛋白与β-actin蛋白表达比为0.88±0.23,均高于NC组的(4.87±0.75)mmol/L、0.27±0.17和0.44±0.21,差别有统计学意义(均P＜0.05),DI组与DA组大鼠甲状腺组织RAGEmRNA和蛋白表达分别为0.60±0.22、0.67±0.27和0.38±0.20、0.45±0.17,均低于DM组(均P＜0.05).结论:DM大鼠甲状腺组织RAGEmRNA和蛋白表达增高;积极地控制血糖、阻断终末糖基化产物的形成有利于抑制甲状腺组织RAGE高表达.     

西红花酸对晚期糖化终产物诱导内皮细胞晚期糖基化终产物受体表达的抑制作用

目的：研究西红花酸对晚期糖基化终产物（AGE）诱导牛内皮细胞（BEC）中晚期糖基化终产物受体（RAGE）mRNA表达的抑制作用,并探讨其可能机制。方法：不同浓度的西红花酸（1、0.1、0.01μmol/L）预孵BEC细胞12h后,用AGE（100mg/L）刺激细胞12h,RT-PCR法测定RAGEmRNA的表达水平;ELISA法测定细胞间黏附分子-1（ICAM-1）的表达;试剂盒分别检测胞外超氧阴离子和硫代巴比妥酸反应产物（TBARS）浓度;同时,还用2,7-二氯荧光素（DCFH）测定了胞内H2O2的浓度,并用罗丹明123（Rh123）荧光法及MTT法分别检测细胞线粒体膜电位（MMP）水平和其琥珀酸脱氢酶（MSDH）的活性。结果：与AGE模型组相比,西红花酸能显著抑制RAGE mRNA的表达（P〈0.05）,降低胞外超氧阴离子和TBARS（P〈0.01或P〈0.05）及胞内H2O2水平;结果还显示,西红花酸能提高细胞MMP水平和MSDH活性。对ICAM-1蛋白表达也有抑制作用,且呈时间和剂量依赖性。结论：西红花酸可能通过清除AGE与RAGE结合产生的活性氧（ROS）来抑制RAGE mRNA的高表达。提示西红花酸对糖尿病血管病变有潜在的治疗价值。     

槲皮素脂质体对糖尿病大鼠肾脏糖基化终产物及其受体表达的影响

摘要： 目的 观察槲皮素脂质体 （LQ） 对糖尿病大鼠肾脏糖基化终产物 （AGEs） 及其受体 （RAGE） 表达的影响。方法 采用旋转蒸发法制备槲皮素脂质体, 高糖高脂饲料联合腹腔注射链脲佐菌素 （STZ） 建立 2 型糖尿病大鼠模型, 并随机分为糖尿病模型组 （DM 组）, 槲皮素脂质体低 （LQ-L）、 中 （LQ-M）、 高 （LQ-H） 剂量组, 氨基胍 （AG） 对照组（AG 组）, 另设正常组 （N 组）。灌胃治疗 8 周后测定各组大鼠血糖、 体质量、 肾脏肥大指数 （KI）、 血尿素氮 （BUN）、 血肌酐 （Scr）, ELISA 法测血清 AGEs 表达和 24 h 尿微量白蛋白, PAS 染色观察肾脏病理改变, 免疫组化测肾组织 AGEs 表达, RT-PCR 检测肾皮质 RAGE mRNA 表达水平。结果 与 N 组比较, DM 组大鼠血糖、 KI、 BUN、 Scr、 血清 AGEs 和 24 h 尿微量白蛋白显著升高, 体质量明显降低; 肾小球体积萎缩, 基底膜增厚; 肾组织 AGEs 和 RAGE mRNA 表达增高 （均 P < 0.05）。与 DM 组比较, LQ 各剂量组大鼠血糖、 KI、 BUN、 Scr、 血清 AGEs 和 24 h 尿微量白蛋白均降低, 体质量增加; 病理改变明显减轻; 肾组织 AGEs 和 RAGE mRNA 表达降低, 以中剂量组作用更明显 （均 P < 0.05）。结论 LQ 可抑制蛋白质非酶糖基化反应, 从而减少肾组织 AGEs 生成及 RAGE mRNA 表达水平, 对糖尿病大鼠肾脏具有保护作用。     

糖基化终产物对人脐静脉内皮细胞基质金属蛋白酶表达的影响

目的 观察内皮细胞糖基化终产物受体(RAGE)的表达以及糖基化终产物(AGEs)对基质金属蛋白酶(MMPs)表达的影响.方法 将人脐静脉内皮细胞随机分为三组:AGEs 200 μg/ml+α-硫辛酸200μmol/L药物干预组(A组)、AGEs 200 μg/ml作用组(B组)、正常对照组(C组).流式细胞术检测细胞表面RAGE表达,RT-PCR分析MMPs的表达变化.结果 内皮细胞表面RAGE呈高表达.与C组相比,B组MMP-1、MMP-7、MMP-9、MMP- 11和MMP-12 mRNA表达上调,而A组能下调AGEs作用下的内皮细胞MMPs的表达.结论 α-硫辛酸能抑制AGEs与RAGE相互作用诱导的MMPs表达,从而有助于减少因动脉斑块破裂引起的急性血管事件的发生.     

Advanced glycation end products and diabetic complications

Diabetic complications are major cause of morbidity and mortality in patients with diabetes. While the precise pathogenic mechanism(s) underlying conditions such as diabetic retinopathy, diabetic nephropathy and increased risk of atherosclerosis remain ill-defined, it is clear that hyperglycaemia is a primary factor that initiates and promotes complications. Formation of advanced glycation end products (AGEs) correlate with glycaemic control, and these reactive adducts form on DNA, lipids and proteins where they represent pathophysiological modifications that precipitate dysfunction at a cellular and molecular level. Many of these adducts form rapidly during diabetes and promote progression of a raft of diabetes-related complications. Recent evidence also suggests an important interaction with other pathogenic mechanisms activated within the diabetic milieu. This review outlines the nature of AGE formation in biological systems and highlights accumulative evidence that implicates these adducts in diabetic complications. As more therapeutic agents are developed to inhibit AGE formation or limit their pathogenic influence during chronic diabetes, it is becoming clear that these anti-AGE strategies have an important role to play in the treatment of diabetic patients.     

Protection against advanced glycation end products and oxidative stress during the development of diabetic keratopathy by KIOM-79

Objectives KIOM‐79 is a mixture of 80% ethanol extracts of parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix and Euphorbiae radix. The preventive effect of KIOM‐79 on the development of diabetic keratopathy has been investigated. Methods Seven‐week‐old male Zucker diabetic fatty (ZDF) rats were treated with KIOM‐79 (50 mg/kg body weight) once a day orally for 13 weeks. The thickness of the cornea was measured and the extent of corneal cell death was detected by a terminal deoxynucleotidyl transferase dUTP nick‐end labelling assay. The expression of advanced glycation end products (AGEs), 8‐hydroxydeoxyguanosine, nuclear factor‐kappaB (NF‐κB), Bax and Bcl‐2 were evaluated in corneal tissues. Key findings The administration of KIOM‐79 prevented corneal oedema and apoptotic cell death of corneal cells. The accumulation of AGE in corneal tissues was reduced in ZDF rats treated with KIOM‐79. Moreover, KIOM‐79 attenuated oxidative DNA damage, NF‐κB activation and Bax overexpression in the cornea. Conclusions The results suggested that KIOM‐79 exhibited corneal protective properties by not only reducing oxidative stress but inhibiting the AGEs/NF‐κB downstream signal pathway during the development of diabetic keratopathy.     

Zinc against advanced glycation end products

Advanced glycation end products (AGEs) are destructive compounds with pathogenic importance in age‐related chronic diseases. Zinc has antioxidant, anti‐inflammatory and anti‐apoptotic potential. This study aimed to summarize effects of zinc on AGE formation and AGE‐induced damaging agents. Pubmed, Google scholar, Web of Sciences, and Scopus databases were searched. There was no limitation for publication date. English language original articles (in vitro, experimental and human studies) which examined the effect of external zinc on AGE formation, AGE‐induced apoptosis, or oxidative stress in mammals were included. To review the effect of zinc on AGE generation, the search keywords were as follows: “zinc” in title and “AGEs” or “methylglyoxal” or “pentosidine” or “carboxymethyllysine” or “glucosylation” or “carbonyl stress” or “AGEs‐induced apoptosis or oxidative stress or inflammation” in title/abstract. In total, 90 titles and abstracts were identified. Fifty‐two studies were screened after duplicates were removed. Six articles were chosen for review following analysis of both titles and summaries. Finally, based on intensive critical appraisal, 5 articles were included in the study. The evidence presented indicates that zinc has anti‐glycation, anti‐oxidative and anti‐apoptotic effects. Zinc insufficiency may stimulate AGEs formation. Whereas, zinc supplementation could inhibit formation of AGEs, AGE‐induced cell apoptosis and oxidative stress status, and protein carbonyl formation possibly through various signalling pathways.     

Beneficial effect of Azadirachta indica on advanced glycation end-product in streptozotocin-diabetic rat

Context: Both oxidation and hyperglycemia cause increased glycation and the formation of advanced glycation end-products (AGEs) which underlie the complications of diabetes.

Objective: The goal of this article is to determine the effect of the chloroform extract from leaves of Azadirachta indica A. Juss; (Meliaceae) (AI) on the formation of glycated protein.

Materials and methods: Chloroform extract was subjected to in vitro bioassays to evaluate advanced glycation end-products formation. Bovine serum albumin (BSA)-glucose, BSA-methylglyoxal, Amadori-rich protein, glycated hemoglobin, oxidation, and glycation of LDL were determined. Doses of AI of 200?mg/kg/d by oral gavage were administered once daily for 30?d, at streptozotocin-induced diabetic rats. After this period, renal damage (TBARS), glucose, methylglyoxal, glycolaldehyde, and tail tendon collagen were investigated.

Results and discussion: AI exhibits protective action in BSA against glycation formation, GHb, protein levels, and LDL against glycation and oxidation. The renal glucose level decreases a 3.9?mg/g wet tissue. TBA-reactive substance showed a significant decrease to 1.82?mmol/mg protein. In addition, AI showed inhibitory activity against AGEs formation, methylglyoxal, and glycolaldehyde levels in kidney. Treatment with AI in rat tail tendon produced a reduction in cross-linking of collagen proteins. The antiglycation activities of A. indica were attributed in part to their antioxidant activity. AI alleviated oxidative stress under diabetic conditions through the inhibition of lipid peroxidation prevents the onset renal damage.

Conclusion: We found that A. indica is an inhibitor AGE formation, and oxidative stress with a renoprotective effect, which are considered to play important roles in diabetic kidney disease.     

鸡矢藤提取物对STZ致糖尿病小鼠肾脏的氧化应激作用和晚期糖基化终产物的影响

目的：研究鸡矢藤提取物（EPS）对链脲佐菌素（STZ）所致糖尿病肾病小鼠的疗效观察。方法：雄性昆明小鼠适应性喂养后尾静脉注射150 mg·kg^-1 STZ,72 h后检测小鼠空腹血糖（FBG）以建立糖尿病模型。糖尿病小鼠随机分为5组：模型对照组,二甲双胍阳性对照组,EPS低、中、高剂量组（2.5,5,10 g·kg^-1）。另设空白对照组。各组小鼠连续灌胃给药4周,空白和模型对照组给予等量生理盐水。末次给药后测定小鼠FBG,收集尿液,检测24 h尿蛋白含量;测定血清中肌酐（Cr）、尿素氮（BUN）和总胆固醇（TC）的含量;检测肾脏组织中丙二醛（MDA）含量,超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）活性以及晚期糖基化终产物（AGE）水平;HE染色法观察肾脏病理学变化。结果：与模型对照组比较,EPS能显著降低糖尿病小鼠的FBG,并明显降低血清生化指标,降低肾脏组织中MDA、AGE含量和增强SOD、GSH-Px活性,改善肾小管空泡变性和肾小球萎缩。结论：鸡矢藤提取物能有效降低糖尿病肾病小鼠血糖,改善肾功能状态,对STZ所致糖尿病小鼠的肾脏保护作用可能与其能降低AGE的积聚、改善组织的氧化应激状态有关。     

碧罗芷体外抑制蛋白糖化终末产物生成作用的研究

目的　应用体外蛋白糖化反应系统 ,确定碧萝芷抑制蛋白糖化终末产物生成的作用。方法　对照组将葡萄糖与牛血清白蛋白分别在 37、50、70℃共同孵育 ,实验组则加入不同剂量的碧萝芷或氨基胍。在不同时间取孵育样品用荧光分光光度计检测其荧光强度代表为蛋白糖化终末产物的生成量。结果　在本体外系统中 ,蛋白糖化产物的生成与孵育温度及时间呈正相关。碧萝芷在 0 3～ 2 0 g·L- 1 剂量范围内可有效抑制蛋白糖化终末产物的生成 ;其抑制作用相当于同剂量的氨基胍。结论　具有抗氧化作用的植物提取物碧萝芷在体外可有效抑制蛋白糖化终末产物的生成     

非酶糖基化抑制剂的体外筛选方法

目的:建立非酶糖基化抑制剂(NEGI)的体外筛选模型并筛选NEGI.方法:依据非酶糖基化(NEG)致衰老假说,用酶基糖基化终产物(AGE)多克隆抗体建立体外NEGI筛选模型.采用竞争性AGE-ELISA方法定量测定AGE的含量.结果:从60余种中草药组分、合成化合物中筛选得到了3种NEGI,AG2070为化学合成的化合物,INEG-1和INEG-2都属于中药多糖,在结构上与其他NEGI都不同.这3种抑制剂在体外实验中均显示出明显的抑制AGE形成的能力.结论:NEGI的体外筛选模型是可行的.     

Ferulsinaic acid attenuation of advanced glycation end products extends the lifespan of Caenorhabditis elegans

Objectives Ferulsinaic acid is the first member of a new rearranged class of sesquiterpene coumarins of the genus Ferula. The genus Ferula can be used for the treatment of skin infections, hysteria and for stomach disorders, such as a febrifuge and a carminative agent. The effect of ferulsinaic acid on the lifespan of the nematode Caenorhabditis elegans has been examined. Novel data explaining the effect of ferulsinaic acid on the lifespan of C. elegans and its antioxidant power were obtained. Methods C. elegans was cultivated under standard laboratory conditions in absence and presence of different ferulsinaic acid. Also, animals were cultivated under heat and chemical stress conditions in absence and presence of ferulsinaic acid. Life span assay, determination of protein concentration, assay of malondialdehyde and ELISA for determination of AGEs were performed. Key findings Under standard laboratory conditions and in presence of ferulsinaic acid (500 nm , 10 µm and 100 µm ), mean life span of wild type animals was significantly lengthened in a dose‐dependent manner from 18.64 ± 0.19 days (control) to 19 ± 0.19 (P = 0.695), 20.76 ± 0.25 (P = 0.043) and 22.3 ± 0.29 (P = 0.0291), respectively. Interestingly, in C. elegans resistance for heat stress at 35°C and oxidative stress induced by paraquat were significantly improved with ferulsinaic acid. Ferulsinaic acid was found to significantly attenuate both lipid peroxidation and the formation of advanced glycation end products in the wild‐type animals under standard laboratory conditions. Conclusions Ferulsinaic acid had therapeutic efficacy as an antioxidant with the possibility of its use as an antioxidant drug.     

RAGE在结肠癌和正常结肠组织的表达差异

目的研究晚期糖基化终末产物受体蛋白(RAGE)在结肠癌和正常结肠组织中的表达差异。方法采用实时荧光定量PCR法、Western blot法分别从mRNA水平、蛋白水平检测12例结肠癌患者新鲜手术切除标本中RAGE表达。另取60例结肠癌组织标本和10例正常结肠组织标本,采用免疫组织化学链霉素抗生物素蛋白-过氧化物酶(SP)法检测RAGE表达。分析表达差异及其与临床病理因素的关系。结果 RAGE定位于正常组织及癌组织的细胞质,在癌组织中的表达明显增多(P<0.05)。RAGE的表达与结肠癌的组织分化程度呈负相关,与TNM分期呈正相关。RAGE在低分化、Ⅲ和Ⅳ期结肠癌组织中阳性表达率增高。结论 RAGE在结肠癌中的表达与其侵袭能力存在相关性。     

Male infertility: A proximate look at the advanced glycation end products

Advanced glycation end products (AGEs) are products of cascades of non-enzymatic glycosylation. They are formed over a period of hours to days, depending on the protein lifetime. AGEs acts by independently producing reactive oxygen species (ROS) or by binding to their receptors. Binding of AGE to the receptor for advanced glycation end products (RAGE) has been shown to play a role in physiological processes, including lung homeostasis, bone metabolism, neuronal systems and the immune system. When in excess, they take part in the pathogenesis of diseases such as diabetes mellitus, cardiovascular diseases, neurodegenerative diseases, and etcetera.The cause of male infertility is considered unexplained in many cases, suggesting that there are gaps in the mechanistic knowledge of sperm production and function, especially, pathways involved in the physiochemical protein regulation of spermatogenesis. It is therefore important to consider areas of research highlighting protein modification and identification and their implication for male fertility.