Circulating levels of advanced glycation end products in females with polycystic ovary syndrome:a meta-analysis

Polycystic ovary syndrome(PCOS)is a common endocrine disorder characterized by a hormonal imbalance that affects females of reproductive age.The association between advanced glycation end products(AGEs)and PCOS has attracted considerable attention in recent years,highlighting the potential of AGEs as biomarkers for this disorder.In the present systematic review and meta-analysis,we aimed to examine the association between AGEs and PCOS,evaluate their potential as biomarkers,and improve our understanding of the pathophysiology of PCOS and its associated metabolic complications.A literature search was performed using various databases from January 2000 to March 2023 to identify relevant studies investigating the association between AGEs and PCOS.Pooled effect estimates were calculated using standardized mean differences(SMD)with 95%confidence intervals(CIs).Sub-group and meta-regression analyses were performed to examine potential sources of heterogeneity.The meta-analysis included six studies with a total of 623 participants.Our results revealed a significant increase in circulating AGE levels in females with PCOS compared to healthy females(SMD=2.35;95%CI:1.10-3.60;P<0.001).Significant heterogeneity was observed between the studies(I2=96.37%;P<0.001),indicating the presence of several factors influencing the association.Sub-group analyses based on body mass index,age,and homeostatic model assessment for insulin resistance indicated differential effects of AGEs on specific sub-groups.This systematic review and meta-analysis support the association between elevated AGE levels and PCOS,thereby suggesting the potential role of AGEs as biomarkers in PCOS.

CML、sRAGE、esRAGE对冠心病动脉粥样硬化的诊断价值

目的探讨ε-羧甲基赖氨酸(CML)、可溶性晚期糖基化终产物受体(sRAGE)、内源性可溶性晚期糖基化终产物受体(esRAGE)对冠心病动脉粥样硬化的诊断价值。方法2020年6月至2022年12月,于新疆维吾尔自治区人民医院选取冠心病患者100例作为观察组。同时选取100例在我院体检的正常人作为对照组。比较两组ε-羧甲基赖氨酸(CML)、可溶性晚期糖基化终产物受体(sRAGE)和内源性分泌性晚期糖基化终产物受体(esRAGE)水平。应用受试者操作者特征(ROC)曲线评价CML、sRAGE、esRAGE的诊断水平,并联合检测冠心病动脉粥样硬化。结果与对照组相比,观察组血清CML及sRAGE水平明显升高,而esRAGE水平呈下降趋势。血清CML、sRAGE和esRAGE可准确诊断冠心病动脉粥样硬化,联合检测灵敏度(90.91%)、特异性(68.66%)、准确性(76.00%)、阳性预测值(58.82%)、阴性预测值(93.88%)、ROC曲线下面积(AUC)(0.922)较高。结论CML、sRAGE、esRAGE与冠心病动脉粥样硬化有关,有利于临床诊断和治疗。

Expression of receptor for advanced glycosylation end products(AGEP)and inhibition of AGEP-induced cytosolic calcium elevationbydiltiazeminculturedrataorticsmoothmusclecels

目的：探讨培养的主动脉平滑肌细胞（ＡＳＭＣ）上是否表达糖基化终产物（ＡＧＥＰ）高亲性受体和地尔硫对ＡＧＥＰ升高胞浆游离钙的抑制．方法：用放射配基结合方法研究ＡＳＭＣ与ＡＧＥＰ的相互作用；用钙离子荧光指示剂Ｆｕｒａ２ＡＭ测定ＡＳＭＣ胞浆游离钙．结果：ＡＳＭＣ上有ＡＧＥＰ高亲和性受体表达，其解离常数为６５３±１５ｎｍｏｌ·Ｌ－１，最大结合容量１５７±００４ｎｍｏｌ／ｇ细胞蛋白；通过该受体介导，平滑肌细胞可内化、代谢ＡＧＥＰ．ＡＧＥＰ使胞浆游离钙呈浓度依赖性升高；地尔硫呈时间、浓度依赖性抑制此效应．结论：大鼠ＡＳＭＣ上有ＡＧＥＰ高亲和性受体表达；地尔硫可抑制ＡＧＥＰ介导的胞浆游离钙升高．

芦丁调控miR-155和HMGB1/RAGE通路对糖尿病视网膜病变大鼠炎性反应的影响

目的:探讨芦丁对糖尿病视网膜病变大鼠炎性反应的影响及其机制。方法:采用腹腔注射链脲佐菌素的方法制备糖尿病大鼠模型,将造模成功的大鼠随机分为模型组(0.9%氯化钠溶液灌胃)和芦丁低、中、高剂量组[分别以50、100、150 mg/(kg·d)芦丁灌胃],并取正常大鼠作为对照组(0.9%氯化钠溶液灌胃),每组20只,持续给药12周后,比较各组大鼠视网膜组织中伊凡斯兰渗透量、神经节细胞凋亡和微小RNA(miR)-155、高迁移率族蛋白1(HMGB1)、晚期糖基化终产物受体(RAGE)mRNA表达水平,以及炎症因子水平。结果:对照组、模型组和芦丁低、中、高剂量组中伊凡斯兰渗透量分别为(1.61±0.31)μg/g、(12.84±1.24)μg/g、(9.85±0.62)μg/g、(6.80±0.53)μg/g、(2.87±0.51)μg/g,神经节细胞凋亡指数分别为(1.09±0.45)%、(30.96±2.50)%、(24.65±2.48)%、(18.61±1.41)%、(8.36±0.54)%,miR-155表达水平分别为(0.38±0.03)、(1.92±0.15)、(1.55±0.12)、(1.09±0.10)、(0.55±0.05),HMGB1 mRNA表达水平分别为(0.26±0.03)、(0.77±0.05)、(0.68±0.04)、(0.57±0.04)、(0.34±0.03),RAGE mRNA表达水平分别为(0.18±0.02)、(0.67±0.04)、(0.58±0.03)、(0.45±0.03)、(0.23±0.02)。模型组和对照组比较,伊凡斯兰渗透量、凋亡指数和miR-155、HMGB1、RAGE mRNA水平均升高(均P<0.05);芦丁低、中、高剂量组中上述指标呈剂量依赖性降低(均P<0.05)。模型组、对照组与芦丁低、中、高剂量组,芦丁各组的炎症因子水平低于模型组(均P<0.05)。结论:芦丁可保护糖尿病大鼠视网膜损伤,延缓视网膜炎症效应,其作用机制可能与抑制miR-155和HMGB1/RAGE通路有关。

Effects of advanced glycosylation end products on proliferation and cytosolic free calcium in cultured rat aortic smooth muscle cells

目的：研究糖基化终产物（ＡＧＥＰ）对主动脉平滑肌细胞增殖的影响及其与［Ｃａ２＋］ｉ的关系．方法：采用同位素掺入法分别测定ＤＮＡ和蛋白质合成；Ｆｕｒａ２ＡＭ测定［Ｃａ２＋］ｉ．结果：ＡＧＥＰ以浓度、时间相关的方式促进［３Ｈ］ＴｄＲ与［３Ｈ］Ｌｅｕ掺入细胞，随ＡＧＥＰ作用时间、糖化时间延长，掺入率增加明显．ＡＧＥＰ增加［Ｃａ２＋］ｉ，与时间、浓度相关，但随ＡＧＥＰ作用时间延长（４０分钟后）而有所降低，ＢＳＡ修饰中葡萄糖浓度的增加，糖基化时间延长，［Ｃａ２＋］ｉ也呈上升趋势．结论：ＡＧＥＰ刺激平滑肌细胞增殖，并与细胞［Ｃａ２＋］ｉ浓度增加有关．

Intrafollicular Soluble RAGE Benefits Embryo Development and Predicts Clinical Pregnancy in Infertile Patients of Advanced Maternal Age Undergoing In Vitro Fertilization

Soluble receptor for advanced glycation end products（s RAGE） can decoy the toxic AGEs and is considered to be a protective factor.This study aimed to evaluate the correlation between intrafollicular s RAGE levels and clinical outcomes in infertile women of young or advanced maternal age（AMA） undergoing in vitro fertilization（IVF）.A total of 62 young women and 62 AMA women who would undergo IVF were included in this prospective study.The intrafollicular s RAGE concentration was measured to determine its association with the number of retrieved oocytes,fertilized oocytes,high-quality embryos or achievement of clinical pregnancy in young and AMA women,respectively.Besides,correlations between sR AGE and age or follicle-stimulating hormone（FSH） were examined.We found that the intrafollicular s RAGE levels were higher in young patients than those in AMA patients,suggesting that the s RAGE levels were inversely correlated with age.In young patients,sR AGE showed no correlation with the number of retrieved oocytes,fertilized oocytes,high-quality embryos or achievement of clinical pregnancy.But it was found that AMA patients with more retrieved oocytes,fertilized oocytes and high-quality embryos demonstrated higher sR AGE levels,which were a prognostic factor for getting clinical pregnancy independent of age or FSH level.In conclusion,the s RAGE levels decrease with age.Elevated intrafollicular s RAGE levels indicate good follicular growth,fertilization and embryonic development,and successful clinical pregnancy in AMA women,while in young women,the role of s RAGE may not be so predominant.

烟草烟雾通过HMGB1-RAGE途径促进慢性阻塞性肺疾病的发生发展

慢性阻塞性肺疾病(COPD)是一种以进行性气流阻塞为特征的慢性气道疾病。COPD由基因与环境共同作用所致,而烟草烟雾(CS)是COPD发生的主要环境危险因素。CS可通过影响高迁移率族蛋白B1(HMGB1)-晚期糖基化终末产物受体(RAGE)轴导致气道炎症、氧化应激和蛋白酶-抗蛋白酶失衡,最终促进COPD的发生发展。因此,深入研究HMGB1-RAGE途径相关COPD生物标志物可帮助筛查吸烟者中的COPD高危患者,提高COPD早期诊断率。

Advanced glycosylation end products increase diacylglycerol levels in cultured human umbilical vein endothelial cells

To study whether the diacylglycerol (Dia) signaling pathway is stimulated by advanced glycosylation end products (AGEP) and to test the effect of vitamin E and aminoguanidine (AG) on the elevation of Dia induced by AGEP in cultured human umbilical vein endothelial cells (HUVECs) Methods The effects of AGEP on Dia levels in cultured HUVEC were studied with radio enzymatic assay Quantitative measurements of 32 P phosphatidic acid were achieved by thin layer chromatography and autoradiography Results The Dia levels in HUVECs were increased by AGEP modified bovine serum albumin (AGEP BSA) in a dose dependent, biphasic manner The early phase was rapid and transient, peaking at 15?s; the late phase reached the maximal level at 10?min and then decayed slowly Dia levels in HUVEC exposed to different concentrations (50, 100 and 200?mg/L) of AGEP BSA (341±14, 678±16, and 873±18?pmol/L, respectively vs control 225±10?pmol/L) and AGEP BSA samples with various glycosylation times (4, 8 and 12 weeks) were significantly increased (270±12, 394±16, and 556±19?pmol/L) as compared with the controls 50 and 100?mmol/L of vitamin E can reduce AGEP BSA induced Dia levels from 873±18?pmol/L to 764±29 and 441±21?pmol/L in HUVEC, respectively In AG treated (100?mmol/L) groups, the same concentration (100 and 200?mg/L) of AGEP BSA induced elevation of Dia was decreased to 312±8 and 351±13?pmol/L, respectively Glycosylated low density lipoprotein (LDL) did not affect Dia levels Conclusion AGEP causes a robust stimulation of the Dia/protein kinase C pathway in HUVEC Vitamin E can attenuate the AGEP BSA induced elevation of Dia levels AG can suppress the ability of AGEP BSA to increase Dia levels in HUVEC

Food-advanced glycation end products aggravate the diabetic vascular complications via modulating the AGEs/RAGE pathway

The aim of this study was to investigate the effects of high-advanced glycation end products(AGEs) diet on diabetic vascular complications. The Streptozocin(STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia,polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic characteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein(CRP), low density lipoprotein(LDL), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial cells, mesangial cells and podocytes in renal cortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species(ROS) and low-levels of superoxide dismutase(SOD) in serum, heart, and kidneys. It also upregulated RAGE mR NA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes.

Effect of advanced glycosylation end products on activity of protein kinase C in human peripheral blood mononuclear cells

To investigate the effect of advanced glycosylation end products (AGEs) on the activity of protein kinase C (PKC) in human peripheral blood mononuclear cells (PBMC) and to observe whether aminoguanidine (AG) can influence the effect of AGEs Methods After PBMC were isolated from human peripheral blood and incubated with different concentrations of AGEs BSA for various periods, total PKC activity in PBMC was determined by measuring the incorporation of 32 P from [γ 32 P] ATP into a special substrate using Promega PKC assay kit Results AGEs BSA increased the total PKC activity in PBMC from 83 43±6 57?pmol/min/mg protein to 116 8±13 82?pmol/min/mg protein with a peak at 15?min AGEs BSA also increased the total PKC activity in a concentration dependent manner from 83 1±6 4?pmol/min/mg protein (control) to 119 1±13 3?pmol/min/mg protein (control vs AGEs BSA 400?mg/L, P <0 01) Furthermore, AGEs BSA induced an elevation of PKC activity in a glycosylating time related manner, from 80 9±8 2 (control) to 118 3±11 5?pmol/min/mg protein (glycosylation for 12 wk, P <0 01) The total PKC activity stimulated by AGEs BSA pretreated with AG (100, 200?mg/L) was markedly lower than that of AGEs BSA group not pretreated with AG ( P <0 05, P <0 01) Conclusions AGEs BSA increased the total PKC activity in PBMC in a concentration and incubation time dependent manner The ability of AGEs BSA to stimulate PKC activity was markedly decreased by pretreatment of AGEs BSA with AG

Effect of icarisid II on diabetic rats with erectile dysfunction and its potential mechanism via assessment of AGEs, autophagy, roTOR and the NO-cGMP pathway

Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ on diabetic rats with ED and its potential mechanism viathe assessment of advanced glycosylation end products （AGEs）, autophagy, mTOR and the NO-cGMP pathway. Icarisid Ⅱ was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid Ⅱ group, rats were administered icarisid Ⅱ intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure （ICP/MAP）. AGE concentrations, nitric oxide synthase （NOS） activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 Iocalisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid Ⅱ increased ICP/MAP values, the smooth muscle cell （SMC） growth curve, S phase and SMC/collagen fibril （SMC/CF） proportions and decreased Beclin 1 （P〈0.05）. Icarisid Ⅱ significantly increased the proliferative index and p-p70S6K（Thr389） levels and decreased the numbers of autophagosomes and the levels of LC3-11 （P〈0.01）. Icarisid Ⅱ decreased AGE concentrations and increased cGMP concentration, NOS activity （P〈0.05） and cNOS levels （P〈0.01） in the diabetic ED group. Therefore, Icarisid Ⅱ constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.

Expression of platelet-endothelial cell adhesion molecule-1 in human umbilical vein endothelial cells by exposure to advanced glycosylation end products and inflammatory mediators

Objective To determine whether advanced glycosylation end products modified bovine serum albumin (AGEs-BSA) affects endothelial cell lateral junction protein, platelet-endothelial cell adhesion molecule-1 (PECAM-1) in the presence or absence of inflammatory mediators.Methods Cultured human umbilical vein endothelial cells (HUVECs) were exposed to AGEs-BSA for 6, 12, 24, and 36 hours, and exposed to AGEs-BSA glycosylated with different concentrations of glucose, tumor necrosis factord-α (TNF-α), interferon (IFN-γ), TNF-α + IFN-y and AGEs-BSA + TNF-α for 24 hours, respectively. Expression of PECAM-1 mRNA was measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) with β-actin as an internal standard, and sequencing of RT-PCR products was performed to confirm the specificity of amplification for PECAM-1 gene. The endothelial cell surface expression of PECAM-1 was determined by flow cytometry (FCM).Results There were no significant changes in the expression of PECAM-1 mRNA and protein when the cells were exposed to AGEs-BSA with different concentrations or periods ( P>0. 05). However, PECAM-1 expression was reduced in the cells treated with TNF-α, IFN-y, TNF-α + IFN-γ and AGEs-BSA + TNF-α. The level of PECAM-1 treated with AGEs-BSA + TNF-α was lower than that of TNF-α treated alone (P<0. 01).Conclusions AGEs-BSA had no effect on the expression of PECAM-1 mRNA and protein in cultured HUVEC. With the presence of inflammatory mediator TNF-α, AGEs-BSA decreased the level of PECAM-1, which might reduce the adhesion interaction between adjacent endothelial cells, enhance the permeability of endothelial cells, and might be implicated in the endothelial dysfunction and pathogenesis of atherosclerosis in patients with diabetes mellitus. The significance of this phenomenon in intracellular signal transduction remains to be determined.

SR-AⅡ和CD36的表达水平与AGEs及糖尿病并发症的相关性研究

目的:分析糖尿病患者白细胞中清道夫受体SR-AⅡ和CD36的表达水平与血浆晚期糖基化终产物(AGEs)浓度以及糖尿病并发症之间的相关性。方法:收集具有合并症的糖尿病患者抗凝血78例,用荧光分光光度法测定血浆AGEs浓度。用Trizol法提取白细胞RNA,再以RT-PCR法测定SR-AⅡ和CD36的相对表达水平。结果:在测定的糖尿病各合并症中,SR-AⅡ在糖尿病性肾病中表达水平最高,在脂肪肝患者中最低;CD36在脂肪肝患者中最高,在冠心病患者中最低。在高血压患者中这2种受体的表达水平均比较高,但在白内障患者中2种受体的表达相对较低。血浆AGEs浓度与白细胞中CD36表达水平呈负相关(r=-0.89,P<0.01),但与SR-AⅡ的表达为正相关(r=0.82,P<0.05)。结论:血浆高浓度AGEs刺激白细胞中SR-AⅡ表达增加,糖尿病性肾病和脂肪肝分别与SR-AⅡ、CD36的表达增加有密切关系,部分糖尿病患者CD36的表达较低可能是导致他们血浆AGEs水平过高的原因之一。

AGEs对肾小管上皮细胞转分化、1型胶原合成及smad信号通路的影响

目的:观察终末期糖基化终产物(AGEs)对正常大鼠近端肾小管上皮细胞(NRK52E)转分化、colla-genⅠ合成及Sm ads信号通路的影响。方法:应用自制的AGEs(AGE-BSA)刺激NRK52E细胞,采用免疫细胞化学方法检测pm ad2/3核表达情况;ELISA方法检测细胞培养上清TGF-β1的浓度;RT-PCR检测TGF-β1、Sm ad2、Sm ad3和Sm ad7 mRNA的表达;W estern印迹检测α-平滑肌肌动蛋白(SMA)、E-钙粘着糖蛋白(cadherin)和1型胶原(collagenⅠ)蛋白的表达。结果:AGE-BSA刺激15 m in后pSm ad2/3核表达明显增加,于30 m in(68%)和24 h(76%)出现两个高峰,与刺激前及时间匹配的BSA对照组比较均有显著差异(P<0.05);AGE-BSA以时间依赖方式上调TGF-β1、Sm ad2、Sm ad3和Sm ad7 mRNA的表达;NRK52E细胞α-SMA和collagenⅠ蛋白表达高于对照组(P<0.01),E-cadherin蛋白表达低于对照组(P<0.01),细胞上清液TGF-β1的浓度高于对照组(P<0.01)。结论:AGEs可诱导肾小管上皮细胞Sm ads信号通路活化,促进肾小管上皮细胞转分化和细胞外基质collagenⅠ的合成。

北京健康人群AGEs水平测定及其增龄性变化的研究

目的 调查北京地区各年龄段健康人群血清晚期糖基化终末产物（AGEs）水平,分析其与增龄的相关性,比较其与部分老年病人群血清AGEs水平的差异.方法 用F-3000荧光分光光度计测定各年龄段健康人群血清样本荧光值.结果 30～39、40～49、50～59及60～69岁年龄组血清AGEs水平均显著高于20～29岁年龄组（P＜0.05）,在30～69岁区间血清AGEs水平与增龄呈显著正相关（r=0.996,P＜0.000 5）,糖尿病（DM）人群血清AGEs水平显著高于同年龄段健康人群（P＜0.05）.结论 血清AGEs水平可作为北京地区30岁以上健康人群的年龄指征及DM人群初筛的生物学标志.

艾灸对DM性ED大鼠阴茎勃起功能及AGEs影响的研究

目的研究艾灸对糖尿病(DM)性阴茎勃起功能障碍(ED)的作用及其对阴茎晚期糖基化终产物(AGEs)的影响。方法以链脲佐菌素(STZ)诱导DM大鼠模型,再以阿朴吗啡(APO)阴茎勃起实验筛选DM性ED大鼠模型,随机分为模型组、艾灸组,另设一正常对照组。艾灸组取肾俞穴、三阴交穴,以麦粒灸施治,观察艾灸对DM性ED大鼠阴茎勃起、血糖、阴茎晚期糖基化终产物(AGEs)的影响。结果艾灸对DM性ED大鼠血糖有一定的改善作用;能较明显改善其阴茎勃起功能;能改善阴茎中AGEs水平。结论艾灸对DM性ED大鼠阴茎勃起功能有一定作用,这种作用与艾灸改善血糖及阴茎AGEs水平有一定相关性。

AGEs-BSA对人肾系膜细胞分泌RANTES的影响初探

目的 :探讨糖基化终产物 (AGEs)对人肾系膜细胞 (HRMC)分泌正常T细胞表达的调节活化蛋白 (RANTES)的影响。方法 :常规制备糖基化终产物 牛血清白蛋白 (AGEs BSA) ,干预体外培养的HRMC ,用ELISA法检测培养上清RANTES水平。结果 :AGEs BSA(64 0mg·L- 1 )干预HRMC后 8h ,培养液中RANTES水平开始逐步升高 ,于 48h达峰值 ,对照组BSA则未见升高 (P <0 .0 1)。结论

松香酸通过诱导自噬减轻AGEs诱导的心肌H9c2细胞凋亡和内质网应激反应

目的:本文旨在探索松香酸(abietic acid,AA)对晚期糖基化终末产物(advanced glycosylation end products,AGEs)诱导的心肌H9c2细胞凋亡和内质网应激的影响及其相关机制。方法:H9c2细胞分为5组:对照组加入生理盐水处理24 h;AGEs处理组加入AGEs(100 mg/L)处理24 h;AGEs+AA(10、25和50μmol/L)组同时加入AGEs(100 mg/L)和AA(10、25和50μmol/L)处理24 h。MTT法检测H9c2细胞活力。Western blot分析肌红蛋白(myoglobin,Mb)、肌酸激酶MB同工酶(creatine kinase MB isoenzyme,CK-MB)、心肌肌钙蛋白I(cardiac troponin I,c Tn I)、C/EBP同源蛋白(C/EBP homologous protein,CHOP)、cleaved caspase-12、GADD34、Bi P、LC3、P62和beclin 1的蛋白水平。ELISA检测乳酸脱氢酶(lactate dehydrogenase,LDH)活性。流式细胞术分析细胞凋亡。结果:低浓度(低于50μmol/L)的松香酸对H9c2细胞活力无明显影响,高浓度(高于50μmol/L)的松香酸会降低H9c2细胞活力。AGEs组Mb、CK-MB和c Tn I蛋白表达及LDH的水平明显高于对照组(P<0.05);与AGEs组相比,AGEs+AA(10、25和50μmol/L)组Mb、CK-MB和c Tn I的蛋白表达及LDH的表达水平明显降低(P<0.05)。松香酸(10、25和50μmol/L)可抑制AGEs诱导的心肌细胞凋亡、CHOP和cleaved caspase-12蛋白水平的升高及GADD34和Bi P表达的降低(P<0.05)。而且,松香酸(10、25和50μmol/L)可抑制AGEs诱导的心肌细胞LC3-Ⅱ/LC3-Ⅰ比值和beclin 1表达的降低及P62表达的升高(P<0.05)。自噬抑制剂3-甲基腺嘌呤可逆转松香酸对心肌细胞LC3、Mb、cleaved caspase-12和Bi P蛋白水平的影响(P<0.05)。结论:松香酸通过诱导自噬减轻AGEs诱导的心肌H9c2细胞凋亡和内质网应激反应。

糖基化终产物(AGEs)的病理意义及其抑制性药物开发原理的研究进展

糖基化终产物(AGEs)是体内蛋白质与还原糖在无酶条件下发生反应后的产物。AGEs与糖尿病及其并发症、血管疾病、衰老以及肾脏疾病等密切相关。本文从AGEs的产生过程、生理作用的分子机制、病理意义以及采用药物干预糖基化终产物的形成和生物学效应等方面进行了综述。

糖尿病大鼠并发牙周炎血清AGEs浓度变化的研究

目的:观察分析糖尿病牙周炎大鼠血清中糖基化终末产物(AGEs)的浓度变化。方法:2月龄雄性Wistar大鼠32只随机分为糖尿病牙周炎组(DP组)、糖尿病组(DM组)、牙周炎组(P组)、对照组(N组)各8只。采用一次性腹腔注射链脲佐菌素(STZ)的方法诱导糖尿病大鼠模型,用正畸结扎丝结扎下颌磨牙牙颈部加高糖软食的方法建立牙周炎大鼠模型,2种方法结合建立糖尿病牙周炎大鼠模型。实验的第4周和第6周处死大鼠,取下颌骨做病理切片HE染色,酶联免疫吸附试验(ELISA)法检测血清中的AGEs。结果:DM组和DP组大鼠出现多食多饮多尿体质量相对减轻的症状,血糖大于16.7mmol/L;4组大鼠牙周袋探诊深度值DP组与DM组、P组、N组,P组与DM组、N组之间差别均有统计学意义(P<0.05);DP组大鼠第6周出现牙槽骨重度吸收,形成骨下袋牙周炎症状;第6周DP组与N组、P组,DM组与P组、N组血清AGEs比较差别有统计学意义(P<0.05)。糖尿病牙周炎大鼠牙周袋探诊深度与血清AGEs浓度呈正相关(r=0.848,P<0.05)。结论:糖尿病合并牙周炎大鼠血清中AGEs水平明显升高。