Serum vascular endothelial growth factor receptor-2 and adropin levels in age-related macular degeneration

AIM： To investigate the serum levels of vascular endothelial growth factor receptor-2（VEGFR-2） and adropin in age-related macular degeneration（AMD）patients.·METHODS： Ninety-eight AMD patients were included in the study. Seventy-eight age- and sex-matched healthy volunteers were recruited as the control group.Fundus florescein angiography and optical coherence tomography were performed to assess the posterior segment details. Serum VEGFR-2 and adropin levels were measured using enzyme-linked immunosorbent assays and compared between the study groups.· RESULTS： AMD group had significantly increased foveal retinal thickness, serum LDL and HDL levels and significantly decreased subfoveal choroidal thickness（P =0.01, 0.047, 0.025 and 〈0.001, respectively）. Serum VEGFR-2level revealed a significant decrease in AMD patients compared to controls（26.48 ±6.44 vs 30.42 ±7.92 ng/m L,P 〈0.001）. There was an insignificant increase in serum adropin level in AMD patients（6.17±3.19 vs 5.79±2.71 ng/m L,P =0.4）. Serum level of VEGFR-2 in AMD patients had a significant negative correlation with foveal retinal thickness（r =-0.226, P =0.025） and a significant positive correlation with subfoveal choroidal thickness（r=0.2, P=0.048）.·CONCLUSION： The current study demonstrated that the decreased serum VEGFR-2 level may be considered in the development of AMD. Adropin does not seem to play a role in the pathogenesis of AMD.

Vascular endothelial growth factor B inhibits insulin secretion in MIN6 cells and reduces Ca2+ and cyclic adenosine monophosphate levels through PI3K/AKT pathway

BACKGROUND Type 2 diabetes(T2 D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance,resulting in an increase in blood glucose.However,the mechanism involved in this lack of insulin secretion is unclear.The level of vascular endothelial growth factor B(VEGF-B) is significantly increased in T2 D patients.The inactivation of VEGF-B could restore insulin sensitivity in db/db mice by reducing fatty acid accumulation.It is speculated that VEGF-B is related to pancreatic β-cell dysfunction and is an important factor affecting β-cell secretion of insulin.As an in vitro model of normal pancreatic β-cells,the MIN6 cell line can be used to analyze the mechanism of insulin secretion and related biological effects.AIM To study the role of VEGF-B in the insulin secretion signaling pathway in MIN6 cells and explore the effect of VEGF-B on blood glucose regulation.METHODS The MIN6 mouse pancreatic islet β-cell line was used as the model system.By administering exogenous VEGF-B protein or knocking down VEGF-B expression in MIN6 cells,we examined the effects of VEGF-B on insulin secretion,Ca2+ and cyclic adenosine monophosphate(cAMP) levels,and the insulin secretion signaling pathway.RESULTS Exogenous VEGF-B inhibited the secretion of insulin and simultaneously reduced the levels of Ca2+ and cAMP in MIN6 cells.Exogenous VEGF-B also reduced the expression of phospholipase C gamma 1(PLCγ1),phosphatidylinositol 3-kinase(PI3 K),serine/threonine kinase(AKT),and other proteins in the insulin secretion pathway.Upon knockdown of VEGF-B,MIN6 cells exhibited increased insulin secretion and Ca2+ and cAMP levels and upregulated expression of PLCγ1,PI3 K,AKT,and other proteins.CONCLUSION VEGF-B can regulate insulin secretion by modulating the levels of Ca2+ and cAMP.VEGF-B involvement in insulin secretion is related to the expression of PLCγ1,PI3 K,AKT,and other signaling proteins.These results provide theoretical support and an experimental basis for the study of VEGF-B in the pathogenesis of T2 D.

达格列净对2型糖尿病非增殖期视网膜病变的影响

目的:探讨达格列净对2型糖尿病非增殖期视网膜病变(non-proliferative diabetic retinopathy,NPDR)的影响。方法:选取2021年10月—2023年6月湖南师范大学附属湘东医院收治的88例2型糖尿病NPDR患者。随机将其分为观察组及对照组,各44例。两组均给予常规降糖治疗,观察组加用达格列净治疗。比较两组治疗前后血糖指标及相关指标。分析血管内皮生长因子(vascular endothelial growth factor,VEGF)与血糖波动指标的相关性。结果:治疗后,两组空腹血糖(fasting blood glucose,FBG)、餐后2 h血糖(2 h postprandial blood glucose,2 h PBG)、糖化血红蛋白(glycosylated hemoglobin,HbA1c)、血糖水平标准差(standard deviation of blood glucose,SDBG)、餐后血糖波动幅度(postprandial glucose excursion,PPGE)、最大血糖波动幅度(large amplitude glycemic excursion,LAGE)均下降,观察组SDBG、PPGE、LAGE均低于对照组,差异有统计学意义(P<0.05)。治疗后,两组VEGF、黄斑中心凹厚度均下降,最佳矫正视力(best-corrected visual acuity,BCVA)升高,观察组VEGF、黄斑中心凹厚度均低于对照组,BCVA高于对照组,差异有统计学意义(P<0.05)。Pearson相关性分析结果显示:VEGF与SDBG、PPGE、LAGE均呈正相关(P<0.05)。结论:达格列净能够改善血糖波动,降低VEGF水平,对2型糖尿病NPDR有保护作用。

Effects of endostatin on expression of vascular endothelial growth factor and its receptors and neovascularization in colonic carcinoma implanted in nude mice

AIM:To investigate the antiangiogenic effects of endostatin on colonic carcinoma cell line implanted in nude mice and its mechanism. METHODS:Nude mice underwent subcutaneous injection with LS-174t colonic carcinoma cell line to generate carcinoma and were randomly separated into two groups.Mice received injection of vehicle or endostatin every day for two weeks. After the tumor was harvested,the tumor volumes were determined,and the expressions of CD34,VEGF and FIk-1 were examined by immunohistochemical method. RESULTS:Tumor volume was significantly inhibited in the endostatin group(84.17%)and tumor weight was significantly inhibited in the endostatin group(0.197±0.049) compared to the control group(1.198±0.105)(F=22.56, P=0.001),microvessel density(MVD)was significantly decreased in the treated group(31.857±3.515)compared to the control group(100.143±4.290)(F=151.62,P<0.001). Furthermore,the expression of FIk-1 was significantly inhibited in the treated group(34.29%) ompared to the control group(8.57%)(X^2=13.745,P=0.001).However no significant decrease was observed in the expression of vascular endothelial growth factor(VEGF)between these two groups(X^2=0.119,P=0.730). CONCLUSION:Endostatin can inhibit tumor growth and angiogenesis by blocking Vegf/FIk-1 pathway.This experiment provides the theory basis for developing a new anti-carcinoma drug through studying the properties of anti-angiogenesis inhibitors.

Vascular endothelial growth factor A promotes platelet adhesion to collagen Ⅳ and causes early brain injury after subarachnoid hemorrhage

The role of vascular endothelial growth factor A in platelet adhesion in cerebral microvessels in the early stage of subarachnoid hemorrhage remains unclear.In this study,the endovascular puncture method was used to produce a rat model of subarachnoid hemorrhage.Then,30 minutes later,vascular endothelial growth factor A antagonist anti-vascular endothelial growth factor receptor 2 antibody,10μg,was injected into the right ventricle.Immunohistochemistry and western blot assay were used to assess expression of vascular endothelial growth factor A,occludin and claudin-5.Immunohistochemical double labeling was conducted to examine co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen.TUNEL was used to detect apoptosis in the hippocampus.Neurological score was used to assess behavioral performance.After subarachnoid hemorrhage,the expression of vascular endothelial growth factor A increased in the hippocampus,while occludin and claudin-5 expression levels decreased.Co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells increased,whereas behavioral performance was markedly impaired.After treatment with anti-vascular endothelial growth factor receptor 2 antibody,occludin and claudin-5 expression recovered,while co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells decreased.Furthermore,behavioral performance improved notably.Our findings suggest that increased vascular endothelial growth factor A levels promote platelet adhesion and contribute to early brain injury after subarachnoid hemorrhage.This study was approved by the Biomedical Ethics Committee,Medical College of Xi’an Jiaotong University,China in December 2015.

精神分裂症患者治疗前后的Tie-2、VEGF、PRL变化及其临床意义

目的探讨精神分裂症患者治疗前后血管生成素受体酪氨酸激酶2(Tie-2)、血管内皮生长因子(VEGF)、泌乳素(PRL)的变化及其临床意义。方法回顾性分析2021年7月至2023年9月河南省荣康医院收治的91例精神分裂症患者的临床资料,根据治疗应答情况分为有效组77例和无效组14例。比较两组患者治疗前、治疗2周和4周后的Tie-2、VEGF、PRL水平。应用皮尔逊(Pearson)相关性分析Tie-2、VEGF、PRL与帕利哌酮血药浓度的相关性及其与治疗应答的相关性,绘制受试者工作特征曲线(ROC)评价Tie-2、VEGF及两者联合预测精神分裂症患者治疗后疗效为有效的价值,采用精准-召回曲线评价ROC分析的准确度。结果91例精神分裂症患者治疗后临床痊愈19例,显效48例,好转10例,无效14例,有效率为84.62%;帕利哌酮血药浓度第1~2周呈明显升高趋势,第2周达峰值,第2~4周处于较稳定水平;有效组患者治疗2周和4周后的Tie-2分别为(2153.42±157.83)pg/mL、(2279.88±135.25)pg/mL,明显高于无效组的(1782.19±208.54)pg/mL、(1788.15±223.48)pg/mL,VEGF分别为(422.39±41.65)pg/mL、(461.37±52.80)pg/mL,明显高于无效组的(310.55±24.78)pg/mL、(312.67±27.99)pg/mL,差异均有统计学意义(P<0.05);经Pearson相关性分析结果显示,PRL治疗2周和4周后的变化值与帕利哌酮血药浓度呈显著正相关(r=0.712、0.665,P<0.01);Tie-2和VEGF治疗2周和4周后的变化值与PANSS减分率呈显著正相关(r=0.769、0.752;0.778、0.758,P<0.01);经ROC分析结果显示,Tie-2联合VEGF预测治疗应答的ROC下面积(AUC)为0.899,大于Tie-2(0.769)、VEGF(0.707)(P<0.05);经精准-召回曲线分析结果显示,其AUC为0.901,意味着高精准率和高召回率,采用Tie-2联合VEGF预测治疗应答能为临床医生提供决策支持。结论精神分裂症患者治疗后Tie-2、VEGF变化与帕利哌酮治疗应答有关,联合检测两者可作为预测治疗应答一个方案,为临床医生提供决策支持,PRL变化则与帕利哌酮血药浓度有关,呈现出评估血药浓度和PRL相关不良反应风险的双重应用价值。

Emodin suppresses alkali burn-induced corneal inflammation and neovascularization by the vascular endothelial growth factor receptor 2 signaling pathway

OBJECTIVE:To investigate the effects of emodin on alkali burn-induced corneal inflammation and neovascularization.METHODS:The ability of emodin to target vascular endothelial growth factor receptor 2(VEGFR2)was predicted by molecular docking.The effects of emodin on the invasion,migration,and proliferation of human umbilical vein endothelial cells(HUVEC)were determined by cell counting kit-8,Transwell,and tube formation assays.Analysis of apoptosis was performed by flow cytometry.CD31 levels were examined by immunofluorescence.The abundance and phosphorylation state of VEGFR2,protein kinase B(Akt),signal transducer and activator of transcription 3(STAT3),and P38 were examined by immunoblot analysis.Corneal alkali burn was performed on 40 mice.Animals were divided randomly into two groups,and the alkali-burned eyes were then treated with drops of either 10μM emodin or phosphate buffered saline(PBS)four times a day.Slitlamp microscopy was used to evaluate inflammation and corneal neovascularization(CNV)in all eyes on Days 0,7,10,and 14.The mice were killed humanely 14 d after the alkali burn,and their corneas were removed and preserved at-80℃ until histological study or protein extraction.RESULTS:Molecular docking confirmed that emodin was able to target VEGFR2.The findings revealed that emodin decreased the invasion,migration,angiogenesis,and proliferation of HUVEC in a dose-dependent manner.In mice,emodin suppressed corneal inflammatory cell infiltration and inhibited the development of corneal neovascularization induced by alkali burn.Compared to those of the PBS-treated group,lower VEGFR2 expression and CD31 levels were found in the emodintreated group.Emodin dramatically decreased the expression of VEGFR2,p-VEGFR2,p-Akt,p-STAT3,and p-P38 in VEGF-treated HUVEC.CONCLUSION:This study provides a new avenue for evaluating the molecular mechanisms underlying corneal inflammation and neovascularization.Emodin might be a promising new therapeutic option for corneal alkali burns.

利拉鲁肽在老年2型糖尿病治疗中对患者血糖波动、血脂以及血管内皮功能指标影响的研究

目的 探究老年2型糖尿病患者应用利拉鲁肽的治疗效果。方法 选取2021年1月—2022年12月福建医科大学附属龙岩第一医院收治的52例老年2型糖尿病患者为研究对象,按照治疗方法分为两组,各26例,对照组采用二甲双胍治疗,观察组采用利拉鲁肽治疗,对比两组血糖波动情况、血脂情况以及血管内皮功能变化状况。结果 治疗后,两组患者各项血糖、血脂、内皮素-1水平均降低,且与对照组相比,观察组下降幅度更大,差异有统计学意义(P均<0.05);两组患者血清一氧化氮、血流介导的内皮血管舒张功能指标水平均升高,且与对照组相比,观察组上升幅度更大,差异有统计学意义(P均<0.05)。结论 老年2型糖尿病患者应用利拉鲁肽治疗可改善其血糖、血脂以及血管内皮功能,具有理想效果。

半夏白术天麻汤加减治疗高血压合并颈动脉粥样硬化斑块患者的临床疗效及对其HIF-1α、VEGF、VEGFR2信号通路的影响

目的探讨半夏白术天麻汤加减治疗高血压合并颈动脉粥样硬化斑的疗效及对缺氧诱导因子、血管内皮生长因子、血管内皮生长因子受体(Hypoxia-inducible factor-1 alpha、vascular endothelial growth factor、vas-cular endothelial growth factor receptor 2,HIF-1α、VEGF、VEGFR2)信号通路的影响。方法选取2019年1月—2022年2月期间上海中医药大学附属曙光医院收治的高血压合并动脉粥样硬化斑块患者80例作为研究对象,采用随机数字表法分为对照组和研究组,每组各40例。对照组为常规西医治疗,研究组在对照组基础上联合半夏白术天麻汤加减治疗。连续治疗2个月后,观察比较两组患者治疗前后血压(收缩压和舒张压)、血脂[胆固醇(Cholesterol,TC)、甘油三酯(Triglyceride,TG)、低密度脂蛋白胆固醇(Low density lipoprotein cholesterol,LDL-C)以及高密度脂蛋白胆固醇(High density lipoprotein cholesterol,HDL-C)]、颈动脉内膜中层厚度(Intima-media thick-ness,IMT)、外周血缺氧诱导因子/血管内皮生长因子/血管内皮生长因子受体(Hypoxia-inducible factor-1 alpha、vascular endothelial growth factor、vascular endothelial growth factor receptor 2,HIF-1α、VEGF、VEGFR2)、中医症状积分及两组患者生活质量水平。结果治疗后两组患者收缩压和舒张压均较治疗前降低,差异有统计学意义(P<0.05);且研究组低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者血脂TC、TG、LDL-C指标均较治疗前降低,HDL-C指标较治疗前升高,差异有统计学意义(P<0.05);且研究组TC、TG、LDL-C指标低于对照组,HDL-C指标高于对照组,差异有统计学意义(P<0.05)。治疗后两组患者IMT和中医症状积分均较治疗前降低,差异有统计学意义(P<0.05);且研究组低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者外周血HIF-1α、VEGF、VEGFR2水平均较治疗前降低,差异有统计学意义(P<0.05);且研究组低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者心理功能、社会功能、躯体功能和物质生活状态等GQOLI-74评分均较治疗前升高,差异有统计学意义(P<0.05);且研究组高于对照组,差异有统计学意义(P<0.05)。结论对高血压合并颈动脉粥样硬化斑块患者采用半夏白术天麻汤治疗,有助于改善患者的血压及血脂水平,抑制HIF-1α/VEGF/VEGFR 2信号通路,改善患者临床症状,提升其生活质量水平,值得临床推广应用。

吡格列酮二甲双胍联合度拉糖肽治疗2型糖尿病患者的效果

目的:观察吡格列酮二甲双胍联合度拉糖肽治疗2型糖尿病(T2DM)患者的效果。方法:回顾性分析2021年10月至2022年10月该院收治的96例T2DM患者的临床资料,按照治疗方案不同将其分为对照组和观察组各48例。对照组予以度拉糖肽治疗,观察组在对照组基础上联合吡格列酮二甲双胍治疗,两组均持续治疗3个月。比较两组临床疗效,治疗前后血糖指标[空腹血糖(FBG)、餐后2 h血糖(2hPG)、糖化血红蛋白(HbA1c)]水平、血脂指标[高密度脂蛋白胆固醇(HDL-C)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)]水平、血管内皮功能指标[脂联素(ADPN)、内皮素-1(ET-1)、一氧化氮(NO)]水平,以及不良反应发生率。结果:观察组治疗总有效率为93.75%(45/48),高于对照组的79.17%(38/48),差异有统计学意义(P<0.05);治疗后,观察组FBG、2hPG、HbA1c、TG、LDL-C、TC、ET-1水平均低于对照组,差异有统计学意义(P<0.05);观察组HDL-C、ADPN、NO水平均高于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:吡格列酮二甲双胍联合度拉糖肽治疗T2DM患者可提高治疗总有效率,降低血糖指标水平,改善血脂指标和血管内皮功能指标水平,效果优于单纯度拉糖肽治疗。

养血散寒通脉方治疗血虚寒凝型子宫内膜异位症的临床研究

【目的】观察养血散寒通脉方(由当归四逆加吴茱萸生姜汤加减而成)治疗血虚寒凝型子宫内膜异位症(EMS)的临床疗效。【方法】将120例血虚寒凝型EMS患者随机分为研究组和对照组,每组各60例。研究组给予养血散寒通脉方治疗,对照组给予少腹逐瘀颗粒治疗,疗程为3个月,并于疗程结束后随访1年。观察2组患者治疗前后各种疼痛评分[包括经期腹痛视觉模拟量表(VAS)评分和痛经、非经期盆腔痛、性交痛、盆腔压痛、骶韧带结节触痛分级评分]、卵巢子宫内膜异位囊肿大小及血清糖类抗原125(CA125)、血管内皮生长因子(VEGF)、可溶性细胞间黏附分子1(SICAM-1)、基质金属蛋白酶9(MMP-9)、组织金属蛋白酶抑制因子2(TIMP-2)水平的变化情况,并观察2组患者的临床疗效、安全性、复发情况及妊娠情况。【结果】(1)研究过程中,研究组脱落3例,对照组脱落5例,最终共112例患者纳入统计分析,其中研究组57例,对照组55例。(2)治疗3个月后,研究组的总有效率为92.98%(53/57),对照组为85.45%(47/55),组间比较,研究组的疗效明显优于对照组(P<0.05)。(3)治疗后,2组患者的各种疼痛评分(包括经期腹痛VAS评分和痛经、非经期盆腔痛、性交痛、盆腔压痛、骶韧带结节触痛分级评分)均较治疗前明显下降(P<0.05),且研究组的下降幅度均明显优于对照组(P<0.05)。(4)治疗后,2组患者的卵巢子宫内膜异位囊肿均略有缩小,但组内治疗前后及治疗后组间比较,差异均无统计学意义(P>0.05)。(5)治疗后,2组患者血清CA125、VEGF、SICAM-1、MMP-9水平均较治疗前下降(P<0.05),血清TIMP-2水平均较治疗前升高(P<0.05),且研究组对血清CA125、VEGF、SICAM-1、MMP-9水平的下降幅度及对血清TIMP-2水平的升高幅度均明显优于对照组(P<0.05)。(6)随访1年,研究组的复发率为30.19%(16/53),明显低于对照组的68.09%(32/47),组间比较,差异有统计学意义(P<0.05)。研究组21例有生育要求,其中14例妊娠,妊娠率为66.67%(14/21);对照组20例有生育要求,其中4例妊娠,妊娠率为20.00%(4/20);组间比较,研究组的妊娠率明显高于对照组,差异有统计学意义(P<0.05)。(7)治疗期间,2组患者均无明显不良反应发生,且患者的血、尿、大便常规及心电图、肝肾功能等安全性指标均无异常变化。【结论】养血散寒通脉方治疗血虚寒凝型EMS患者疗效确切,能够显著缓解患者各种疼痛症状,改善妊娠结局,有效调节血清CA125、VEGF、SICAM-1、MMP-9、TIMP-2水平。

Vitamin D-Binding Protein is Involved in the Pathogenesis of Preeclampsia by Inhibiting the Tyrosine Phosphorylation of Vascular Endothelial Growth Factor Receptor-2 in Endothelial Cells

Objective::The role of Vitamin D-binding protein(DBP)in preeclampsia(PE)pathogenesis is unknown.In this study,we compared the expression of DBP in the placentas of PE patients with the placentas of normotensive pregnant women with placenta previa controls,and aimed to explore the effect of DBP on endothelial cells(ECs)and the underlying mechanism.Methods::DBP expression in placental tissues collected from PE patients and controls was evaluated by immunohistochemistry.The downregulation and upregulation of DBP expression in HTR-8/SVneo cells were examined using DBP-targeting small interfering RNA(siRNA)and DBP-expression vector,respectively.The conditioned media of these DBP-overexpressing and DBP-siRNA HTR-8/SVneo cells were collected and added to human umbilical vein EC(HUVEC)cultures.Angiogenic effects on HUVECs were assessed by tube formation assays,and the proliferation and migration of HUVECs were examined using the Real-Time Cell Analyzer.The expression of vascular endothelial growth factor(VEGF)and VEGF receptor(VEGFR)-2,as well as the phosphorylation of different residues of VEGFR-2 in HUVECs,were determined by western blotting.Results::DBP expression was significantly increased in the placental tissues collected from PE patients.The conditioned medium of DBP-overexpressing HTR-8/SVneo cells potently inhibited tube formation by HUVECs,in addition to their proliferation and migration.Furthermore,treatment of HUVECs with the conditioned medium of DBP-overexpressing HTR-8/SVneo cells decreased the phosphorylation of VEGFR-2 at tyrosine 996,whereas the treatment of these cells with the conditioned medium of DBP-siRNA HTR-8/SVneo cells increased the phosphorylation of VEGFR-2 at tyrosine 951,996,and 1,175.Conclusions::The expression of DBP is increased in the placentas of PE patients.DBP plays potential roles in endothelial dysfunction,which contributes to PE development,by inhibiting tyrosine phosphorylation of VEGFR-2 in ECs.

直肠癌新辅助化疗前后血清VEGF与VEGFR-2的变化及临床意义

目的探讨直肠癌患者新辅助化疗前后血清血管内皮生长因子(VEGF)及血管内皮细胞生长因子受体2(VEGFR-2)水平的变化及临床意义。方法应用ELISA法检测45例直肠癌患者(化疗组)新辅助化疗前后血清VEGF与VEGFR-2的表达水平,并与45例正常健康人(对照组)作比较。结果化疗组新辅助化疗前血清VEGF、VEGFR-2水平均明显高于对照组(P均<0.01)。新辅助化疗8周后,完全缓解及部分缓解组VEGF、VEGFR-2表达水平均较化疗前明显降低(P均<0.05),降低程度明显高于稳定组(P均<0.01);稳定组化疗后VEGFR、VEGF-2较化疗前显著降低(P均<0.05);进展组化疗后VEGF、VEGFR-2水平均较化疗前显著升高(P均<0.05)。化疗前VEGFR水平与VEGF-2表达呈正相关关系(P<0.01)。结论直肠癌患者血清中VEGFR、VEGF-2均高表达。测定直肠癌患者新辅助化疗前后血清VEGFR、VEGF-2水平的变化有助于临床判断化疗效果及肿瘤进程。

表皮生长因子受体和血管内皮生长因子与环氧化酶2在食管癌组织中的表达及其意义

目的研究食管癌中表皮生长因子受体（EGFR）、血管内皮生长因子（VEGF）、环氧化酶2（COX-2）的表达及其与肿瘤组织病理特征之间的关系。方法应用免疫组化的方法分别检测94例食管癌组织和30例邻近正常食管黏膜中EGFR、VEGF蛋白、COX-2蛋白表达水平，并分析三者与肿瘤组织病理特征之间的关系。结果EGFR、VEGF、COXd在94例食管癌组织中阳性表达率分别为69．2％（65／94）、73．4％（69／94）、84．0％（79／94）；而在30例正常食管黏膜中阳性表达率分别为13．3％（4／30）、13．3％（4／30）、3．3％（1／30），2组间表达差异有统计学意义（P〈0．01）；且EGFR、VEGF、COX-2与淋巴结转移和TNM分期有关（P〈0．05）。结论EGFR、VEGF、COXd在食管癌组织中显著表达，且可能参与肿瘤发生、发展，可作为预测食管癌生物学行为的重要参考指标。

2型糖尿病患者空腹血糖、血脂、APN及VEGF与氧化应激的相关性

目的:探讨2型糖尿病肾病(DN)患者空腹血糖(FPG)、血脂、脂联素(APN)、血管内皮生长因子(VEGF)与氧化应激的相关性。方法:120例2型糖尿病(T2DM)患者,依据24 h尿白蛋白(ALB)排泄率(UAER)均分为T2MD组(UAER<20μg/min)、微量ALB尿组(UAER 20μg/min≤~<200μg/min)、大量ALB尿组(RAER≥200μg/min),另选取同期健康体检者40例为对照组;所有受试者与入院或体检当日抽取空腹静脉血,分离血清,采用全自动血生化仪测定总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C),高压液相法测定糖化血红蛋白(Hb Alc);采用葡萄糖氧化酶法测定空腹血糖(FPG),ELISA法测定血清β2-微球蛋白(β2-MG)、APN、VEGF,酶联免疫定量法测定血清同型半胱氨酸(Hcy),免疫比浊法测定血清光抑素C(Cys C),比色法测定血清丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD);留取受试者清晨尿液标本,采用放射免疫分析法测定UAER;采用直线相关分析T2DM患者血清APN、VEGF、FPG、血脂与MDA、GSH-Px、SOD的相关性。结果:与对照组比较,3组DN患者Hb Alc、FPG、UAER、β2-MG、Cys C、Hcy、VEGF及MDA均升高,GSH-Px、SOD降低(P<0.05);3组DN患者血清FPG、UAER、β2-MG、Cys C、Hcy及VEGF及MDA水平随尿ALB水平增加而逐渐升高,APN逐渐降低(P<0.05),大量ALB尿组GSHPx、SOD低于T2MD组和微量ALB尿组(P<0.05);T2DM患者血清APN与MDA呈负相关(r=-0.479,P<0.05),与GSH-Px、SOD呈正相关(r=0.406,0.359,P<0.05);血清VEGF与MDA呈正相关(r=0.571,P<0.01),与GSH-Px、SOD呈负相关(r=-0.446,-0.454,P<0.05);FPG、血脂与MDA呈正相关(r=0.491,r=0.644,P<0.01),与GSH-Px、SOD呈负相关(r=-0.540,-0.836;r=-0.399,-0.492,P<0.05)。结论:T2MD合并DN患者血清FPG、血脂、APN及VEGF水平与机体氧化应激具有显著相关性,其水平变化提示T2MD并发DN的可能。

COX-2和VEGF在口腔黏膜鳞状细胞癌中表达及意义

目的:研究环氧化酶-2(COX-2)、血管内皮生长因子(VEGF)在口腔黏膜鳞状细胞癌组织中的表达,探讨它们之间的相互关系和临床意义。方法:应用免疫组化方法检测COX-2、VEGF在54例口腔黏膜鳞癌组织中的表达,分析它们的表达情况以及各指标之间的相互关系。结果:COX-2与VEGF在口腔黏膜鳞癌组织中蛋白阳性表达率分别为55.6%、62.5%;COX-2与VEGF的表达随着口腔癌病理分级及临床分期的上升而呈上升趋势(P<0.05),且两者之间存在明显的正相关性(P<0.05)。结论:COX-2和VEGF在口腔黏膜鳞癌组织中均高表达,与口腔黏膜鳞癌的生物学行为密切相关,并在其发生发展中起重要作用,有望作为口腔黏膜鳞癌早期诊断和治疗的新靶点。

高血压病和2型糖尿病患者血清损伤ECV-304细胞的比较研究

目的:以高血压病和2型糖尿病为例进行血瘀证血管内皮细胞损伤模型的比较研究,为中医学"异病同证"理论提供实验依据。方法:取对数生长期ECV-304细胞,分组如下:空白对照组(无血清的DMEM组)、糖尿病血瘀证组(糖尿病血瘀证患者血清)和高血压病血瘀证组(高血压病血瘀证患者血清)。采用噻唑蓝比色法(MTT法)观察细胞活性;在倒置相差显微镜、扫描电镜和透射电镜下观察细胞形态的变化;应用放免法测定内皮素(ET)含量;硝酸还原酶法测定一氧化氮(NO)含量;利用双抗夹心酶联免疫法(ELISA)检测各组细胞培养上清液中内皮细胞蛋白C受体(EPCR)、血管内假性血友病因子(vWF)和血栓调节蛋白(sTM)的含量;应用激光扫描共聚焦显微镜,采用Fluo-3/AM作为荧光指示剂观察细胞内游离钙([Ca2+]i)浓度的变化;并采用荧光探针标记的鬼笔环肽染色法观察细胞肌动蛋白微丝分布的差异。结果:(1)MTT结果显示,10%血清作用下,高血压病血瘀证组的细胞活力低于对照组(P<0.05),糖尿病血瘀证组的细胞活力也低于对照组(P<0.05),但高血压病血瘀证组的细胞活力与糖尿病血瘀证组差异无显著(P>0.05);(2)高血压病血瘀证组的ET水平高于对照组(P<0.05),糖尿病血瘀证组也高于对照组(P<0.05),且高血压病血瘀证组的ET水平低于糖尿病血瘀证组(P<0.05);高血压病血瘀证组的NO水平低于对照组(P<0.05),糖尿病血瘀证组也低于对照组(P<0.05),且高血压病血瘀证组的NO水平高于糖尿病血瘀证组(P<0.05);(3)高血压病血瘀证组的EPCR、vWF和sTM含量高于对照组(P<0.05),糖尿病血瘀证组也高于对照组(P<0.05),且高血压病血瘀证组的EPCR水平低于糖尿病血瘀证组(P<0.05);而高血压病血瘀证组的vWF和sTM含量与糖尿病血瘀证组之间差异无显著(P>0.05);(4)高血压病血瘀证组[Ca2+]i高于对照组(P<0.05),糖尿病血瘀证组[Ca2+]i高于对照组(P<0.05),高血压病血瘀证组胞浆内荧光分布不均匀,[Ca2+]i高于糖尿病血瘀证组(P<0.05);(5)高血压病血瘀证组可见细胞骨架微丝减少但排列较为规则,糖尿病血瘀证组的微丝断裂且排列紊乱,二者微丝分布差异显著。结论:高血压病患者血清和糖尿病患者血清对ECV-304细胞骨架、[Ca2+]i及ET、NO和EPCR表达的影响不同,但均能造成ECV-304细胞损伤,这可能是中医学"异病同证"的病理学基础。

糖尿病足2号方对气虚血瘀型脱疽患者血管内皮细胞功能变化的临床研究

目的:探讨糖尿病足2号方对气虚血瘀型脱疽患者血管内皮细胞功能变化的影响。方法:符合纳入标准的69例动脉硬化闭塞症(ASO)患者随机分为观察组(36例)与对照组(33例)。对照组采用血塞通治疗,观察组联合使用血塞通与糖尿病足2号方,两组均治疗30天,观察两组患者临床疗效及治疗前后踝肱比值和VEGF水平的变化。结果:治疗后两组患者ABI和VEGF水平降低,且观察组优于对照组(P<0.05,P<0.01);观察组临床有效率100.00%,对照组有效率90.91%,观察组优于对照组(P<0.05)。结论:血塞通与糖尿病足2号方联用可降低ASO患者ABI比值,下调VEGF水平,改善临床疗效。

COX-2、VEGF、E-cad在乳腺癌中的研究进展

在乳腺癌演变的过程中,环氧化酶2诱导了乳腺癌的发生、发展;血管内皮生长因子促进了肿瘤血管的生成,保证了肿瘤细胞的生长与存活;上皮钙黏蛋白介导同型细胞之间的连接,其表达的降低或缺失可直接引起肿瘤细胞趋向离散,易于从原发灶脱落、转移。因此,检测这三个影响因子的表达和分析它们之间的关系对判断乳腺癌患者预后及指导临床个体化治疗有重要意义,同时也为临床治疗提供了新的思路与策略。

糖维胶囊对2型糖尿病并发微血管病变患者血糖和血脂水平及血管内皮功能的影响

目的探讨糖维胶囊对2型糖尿病(T2DM)并发微血管病变患者血糖和血脂水平及血管内皮功能的影响。方法选择2016年6月至2018年3月郑州市第一人民医院收治的168例T2DM并发微血管病变患者为研究对象,根据治疗方法将患者分为观察组和对照组,每组84例。对照组患者给予门冬胰岛素治疗,观察组患者在对照组治疗基础上给予糖维胶囊治疗。分别于治疗前和治疗后检测2组患者血糖和血脂水平,并使用彩色多普勒超声检查患者血管内皮功能。结果治疗前2组患者空腹血糖(FBG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)水平及胰岛素抵抗指数(HOMA-IR)比较差异均无统计学意义(P>0.05);2组患者治疗后FBG、HbA1c水平及HOMA-IR显著低于治疗前,FINS水平显著高于治疗前(P<0.05);治疗后,观察组患者FBG水平及HOMA-IR显著低于对照组,HbA1c和FINS水平显著高于对照组(P<0.05)。治疗前2组患者血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)及低密度脂蛋白胆固醇(LDL-C)水平比较差异无统计学意义(P>0.05);2组患者治疗后血清TG、TC、LDL-C水平显著低于治疗前,HDL-C水平显著高于治疗前(P<0.05)。治疗后,观察组患者血清TG、TC及HDL-C水平显著高于对照组,LDL-C水平显著低于对照组(P<0.05)。治疗前2组患者肱动脉基础血管内径、反应性充血血管内径及含服硝酸甘油后血管内径比较差异均无统计学意义(P>0.05),2组患者治疗后肱动脉基础血管内径、反应性充血血管内径及含服硝酸甘油后血管内径大于治疗前(P<0.05);治疗后,观察组患者肱动脉基础血管内径、反应性充血血管内径及含服硝酸甘油后血管内径大于对照组(P<0.05)。结论糖维胶囊可以改善T2DM并发微血管病变患者的血糖和血脂水平,提高患者血管内皮功能。