血清骨膜蛋白、血管内皮生长因子与糖尿病视网膜病变的关系
|
摘要
目的探讨骨膜蛋白(periostin,PN)与血管内皮生长因子(vascular endothelial growth factor,VEGF)在糖尿病视网膜病变(diabetic retinopathy,DR)患者血清中的变化及其临床意义。方法收集糖尿病(diabetes mellitus,DM)(病例组53例)患者血清样本,以同期健康体检对象的血清为对照(对照组50名),其中病例组包括无眼底病变的DM患者15例(DM组),NPDR患者18例(NPDR组),PDR患者20例(PDR组),用酶联免疫吸附试验测定各组样本血清中PN、VEGF含量,并分析血清中PN、VEGF与DR的关系。结果病例组和对照组中PN和VEGF差异均有统计学意义(均为P<0.05)。PN、VEGF在四组间差异均有统计学意义(均为P<0.05)。组间两两比较显示,PN在DM组与NPDR组间比较差异无统计学意义(P>0.05),在其余组间比较差异均有统计学意义(均为P<0.05)。VEGF在各组间两两比较差异均有统计学意义(均为P<0.05)。NPDR组和PDR组血清中PN与VEGF均呈正相关(r=0.483、0.509,均为P<0.05)。结论血清PN、VEGF参与了DR的发生发展,并与DR后期新生血管及纤维血管膜形成关系密切。
Objective To explore the changes in the serum periostin( PN) and vascular endothelial grow th factor( VEGF) level in patients with diabetic retinopathy( D R) and the clinical significance. Methods The serum samples from 53 patients with diabetes mellitus( D M) as case group and 50 healthy subjects as control group were collected and compared in this study. And the D Mpatients included 15 patients with D Mwithout fundus lesions( D Mgroup),18 patients with non-proliferative diabetic retinopathy( NPD R,N PD R group) and 20 patients with proliferative diabetic retinopathy( PD R,PD R group). The serum levels of PN and VEGF were analyzed by ELISA assay,and the correlation of D R with serum PN and VEGF levels was evaluated.Results The differences in serum PN and VEGF between the case group and control group were statistically significant( both P < 0. 05). And there were significant difference in PN and VEGF levels among the D Mgroup,N PD R group,PD R group and control group( all P < 0.05). Meanwhile,there was no significant difference in serum PN betw een the D Mgroup and NPD R group( P > 0. 05),but there were statistically significant differences among the other groups( all P < 0. 05). There were statistically significant differences in serum VEGF among the four groups( all P < 0. 05). And finally,positive correlations were found betw een PN and VEGF in the NPD R group and PD R group( r = 0. 483,0. 509,both P < 0. 05). Conclusion PN and VEGF play an active role in the initiation and development of D R,and they have a close correlation with the neovascularization and fibrovascular membrane of the advanced stage of D R.
Objective To explore the changes in the serum periostin( PN) and vascular endothelial grow th factor( VEGF) level in patients with diabetic retinopathy( D R) and the clinical significance. Methods The serum samples from 53 patients with diabetes mellitus( D M) as case group and 50 healthy subjects as control group were collected and compared in this study. And the D Mpatients included 15 patients with D Mwithout fundus lesions( D Mgroup),18 patients with non-proliferative diabetic retinopathy( NPD R,N PD R group) and 20 patients with proliferative diabetic retinopathy( PD R,PD R group). The serum levels of PN and VEGF were analyzed by ELISA assay,and the correlation of D R with serum PN and VEGF levels was evaluated.Results The differences in serum PN and VEGF between the case group and control group were statistically significant( both P < 0. 05). And there were significant difference in PN and VEGF levels among the D Mgroup,N PD R group,PD R group and control group( all P < 0.05). Meanwhile,there was no significant difference in serum PN betw een the D Mgroup and NPD R group( P > 0. 05),but there were statistically significant differences among the other groups( all P < 0. 05). There were statistically significant differences in serum VEGF among the four groups( all P < 0. 05). And finally,positive correlations were found betw een PN and VEGF in the NPD R group and PD R group( r = 0. 483,0. 509,both P < 0. 05). Conclusion PN and VEGF play an active role in the initiation and development of D R,and they have a close correlation with the neovascularization and fibrovascular membrane of the advanced stage of D R.
引文
[1]CAPITO M,RAQUEL S.Angiogenesis and inflammation crosstalk in diabetic retinopathy[J].JCell Biochem,2016,117(11):2443-2453.
[2]YOSHIDA S,NAKAMA T,ISHIKAWA K,NAKAO S,SONOD A K H,ISHIBASHI T.Periostin in vitreoretinal diseases[J].Cell Mol Life Sci,2017,74(23):4329-4337.
[3]Ophthalmology Section of Chinese M edical Association.Guidelines fo r the clinical diagnosis and treatment of diabetic retinopathy in china[J].Chin J Ophthalmol,2014,50(11):851-865.中华医学会眼科学会眼底病学组.我国糖尿病视网膜病变临床诊疗指南[J].中华眼科杂志,2014,50(11):851-865.
[4]ZHANG F J,YI J L,LI J M,LIU Q P.Recent advances in pathological mechanisms of diabetic retinopathy[J].Rec A dv Ophthalmol,2016,36(6):584-587.张凤俊,易敬林,李晶明,刘秋平.糖尿病视网膜病变发病机制研究进展[J].眼科新进展,2016,36(6):584-587.
[5]CHEN X H,WANG Y P,CHEN M Z.Role of VEGF in pathogenesis of diabetic retinopathy and anti-VEGF therapy[J].Rec A dv Ophthalmol,2015,35(7):692-696.陈小红,王云鹏,陈梅珠.VEGF在糖尿病性视网膜病变发病机制中的作用及抗VEGF治疗新进展[J].眼科新进展,2015,35(7):692-696.
[6]NALINI M,RAGHAVULU B V,ANNAPURNA A,AVINASH P,C HAN D I V,SW AT HI N.Correlation of various serum biomarkers with the severity of diabetic retinopathy[J].Diabetes Metab Syndr,2017,11(11):451-454.
[7]DU J H,LI R,XU L,MA R R,LIU J L,CHENG J,et al.Increased serum chemerin levels in diabetic retinopathy of type 2 diabetic patients[J].Curr Eye Res,2016,41(1):114-120.
[8]ZHOU Z W,JU H X,SUN M Z,FU Q P,CHEN H M,JI H B,et al.Serum fetuin-A levels are independently correlated with vascular endothelial grow th factor and C-reactive protein concentrations in type 2 diabetic patients with diabetic retinopathy[J].Clin Chim A cta,2016,455(4):113-117.
[9]LANDRY N M,COHEN S,DIXON I M.Periostin in cardiovascular disease and development:a tale of two distinct roles[J].Basic R es Cardiol,2018,113(1):1-13.
[10]O’DWYER D N,MOORE B B.The role of periostin in lung fibrosis and airw ay remodeling[J].Cell Mol Life Sci,2017,74(23):4305-4314.
[11]MUROTA H,LINGLI Y,KATAYAMA I.Periostin in the pathogenesis of skin diseases[J].Cell Mol Life Sci,2017,74(23):4321-4328.
[12]YOSHIDA S,ISHIKAWA K,ASATO R,ARIMA M,SASSA Y,YO SHID A A,et al.Increased expression of periostin in vitreous and fibrovascular membranes obtained from patients with proliferative diabetic retinopathy[J].Invest Ophthalmol V is Sci,2011,52(8):5670-5678.
[13]LU Y,LIU X,JIAO Y,XIONG X,WANG E,WANG X,et al.Periostin promotes liver steatosis and hypertriglyceridemia through dow nregulation of PPARα[J].JClin Invest,2014,124(8):3501.
[14]LUO Y Y,QU H,WANG H,WEI H L,WU J,DUAN Y,et al.Plasma periostin levels are increased in Chinese subjects with obesity and type 2 diabetes and are positively correlated with glucose and lipid parameters[J].Mediators Inflamm,2016,2016.
[15]ISHIKAWA K,YOSHIDA S,NAKAO S,NAKAMA T,KITA T,ASAT O R,et al.Periostin promotes the generation of fibrous membranes in proliferative vitreoretinopathy[J].FA SEB J,2014,28(1):131-142.
[16]RYU J M,LEE M Y,YUN S P,HAN H J.High glucose regulates cyclin D1/E of human mesenchymal stem cells through T GF-β1 expression via Ca2+/PKC/M APKs and PI3K/Akt/m T O R signal pathw ays[J].JCell Physiol,2010,224(1):59-70.
[17]MOON S W,CHUNG E J,JUNG S A,LEE J H.PDGF stimulation of Müller cell proliferation:C ontributions of c-JN K and the PI3K/Akt pathw ay[J].Biochem Biophys Res Commun,2009,388(1):167-171.
[18]SHAO R,BAO S,BAI X,BLANCHETTE C,ANDERSON R M,D AN G T,et al.Acquired expression of periostin by human breast cancers promotes tumor angiogenesis through up-regulation of vascular endothelial grow th factor receptor 2 expression[J].Mol Cell Biol,2004,24(9):3992-4003.
[19]WATANABE T,YASUE A,FUJIHARA S,TANAKA E.PERIO ST IN regulates M M P-2 expression via theαvβ3 integrin/ER K pathw ay in human periodontal ligament cells[J].Arch O ral Biol,2012,57(1):52-59.
[2]YOSHIDA S,NAKAMA T,ISHIKAWA K,NAKAO S,SONOD A K H,ISHIBASHI T.Periostin in vitreoretinal diseases[J].Cell Mol Life Sci,2017,74(23):4329-4337.
[3]Ophthalmology Section of Chinese M edical Association.Guidelines fo r the clinical diagnosis and treatment of diabetic retinopathy in china[J].Chin J Ophthalmol,2014,50(11):851-865.中华医学会眼科学会眼底病学组.我国糖尿病视网膜病变临床诊疗指南[J].中华眼科杂志,2014,50(11):851-865.
[4]ZHANG F J,YI J L,LI J M,LIU Q P.Recent advances in pathological mechanisms of diabetic retinopathy[J].Rec A dv Ophthalmol,2016,36(6):584-587.张凤俊,易敬林,李晶明,刘秋平.糖尿病视网膜病变发病机制研究进展[J].眼科新进展,2016,36(6):584-587.
[5]CHEN X H,WANG Y P,CHEN M Z.Role of VEGF in pathogenesis of diabetic retinopathy and anti-VEGF therapy[J].Rec A dv Ophthalmol,2015,35(7):692-696.陈小红,王云鹏,陈梅珠.VEGF在糖尿病性视网膜病变发病机制中的作用及抗VEGF治疗新进展[J].眼科新进展,2015,35(7):692-696.
[6]NALINI M,RAGHAVULU B V,ANNAPURNA A,AVINASH P,C HAN D I V,SW AT HI N.Correlation of various serum biomarkers with the severity of diabetic retinopathy[J].Diabetes Metab Syndr,2017,11(11):451-454.
[7]DU J H,LI R,XU L,MA R R,LIU J L,CHENG J,et al.Increased serum chemerin levels in diabetic retinopathy of type 2 diabetic patients[J].Curr Eye Res,2016,41(1):114-120.
[8]ZHOU Z W,JU H X,SUN M Z,FU Q P,CHEN H M,JI H B,et al.Serum fetuin-A levels are independently correlated with vascular endothelial grow th factor and C-reactive protein concentrations in type 2 diabetic patients with diabetic retinopathy[J].Clin Chim A cta,2016,455(4):113-117.
[9]LANDRY N M,COHEN S,DIXON I M.Periostin in cardiovascular disease and development:a tale of two distinct roles[J].Basic R es Cardiol,2018,113(1):1-13.
[10]O’DWYER D N,MOORE B B.The role of periostin in lung fibrosis and airw ay remodeling[J].Cell Mol Life Sci,2017,74(23):4305-4314.
[11]MUROTA H,LINGLI Y,KATAYAMA I.Periostin in the pathogenesis of skin diseases[J].Cell Mol Life Sci,2017,74(23):4321-4328.
[12]YOSHIDA S,ISHIKAWA K,ASATO R,ARIMA M,SASSA Y,YO SHID A A,et al.Increased expression of periostin in vitreous and fibrovascular membranes obtained from patients with proliferative diabetic retinopathy[J].Invest Ophthalmol V is Sci,2011,52(8):5670-5678.
[13]LU Y,LIU X,JIAO Y,XIONG X,WANG E,WANG X,et al.Periostin promotes liver steatosis and hypertriglyceridemia through dow nregulation of PPARα[J].JClin Invest,2014,124(8):3501.
[14]LUO Y Y,QU H,WANG H,WEI H L,WU J,DUAN Y,et al.Plasma periostin levels are increased in Chinese subjects with obesity and type 2 diabetes and are positively correlated with glucose and lipid parameters[J].Mediators Inflamm,2016,2016.
[15]ISHIKAWA K,YOSHIDA S,NAKAO S,NAKAMA T,KITA T,ASAT O R,et al.Periostin promotes the generation of fibrous membranes in proliferative vitreoretinopathy[J].FA SEB J,2014,28(1):131-142.
[16]RYU J M,LEE M Y,YUN S P,HAN H J.High glucose regulates cyclin D1/E of human mesenchymal stem cells through T GF-β1 expression via Ca2+/PKC/M APKs and PI3K/Akt/m T O R signal pathw ays[J].JCell Physiol,2010,224(1):59-70.
[17]MOON S W,CHUNG E J,JUNG S A,LEE J H.PDGF stimulation of Müller cell proliferation:C ontributions of c-JN K and the PI3K/Akt pathw ay[J].Biochem Biophys Res Commun,2009,388(1):167-171.
[18]SHAO R,BAO S,BAI X,BLANCHETTE C,ANDERSON R M,D AN G T,et al.Acquired expression of periostin by human breast cancers promotes tumor angiogenesis through up-regulation of vascular endothelial grow th factor receptor 2 expression[J].Mol Cell Biol,2004,24(9):3992-4003.
[19]WATANABE T,YASUE A,FUJIHARA S,TANAKA E.PERIO ST IN regulates M M P-2 expression via theαvβ3 integrin/ER K pathw ay in human periodontal ligament cells[J].Arch O ral Biol,2012,57(1):52-59.