中华内分泌代谢杂志
中華內分泌代謝雜誌
중화내분비대사잡지
CHINESE JOURNAL OF ENDOCRINOLOGY AND METABOLISM
2014年
12期
1080-1085
,共6页
血糖波动%急性冠状动脉综合征%糖尿病,2型%血管生成素2%内质网应激
血糖波動%急性冠狀動脈綜閤徵%糖尿病,2型%血管生成素2%內質網應激
혈당파동%급성관상동맥종합정%당뇨병,2형%혈관생성소2%내질망응격
Glucose fluctuations%Acute coronary syndrome%Diabetes mellitus,type 2%Angiopoietin 2%Endoplasmic reticulum stress
目的 探讨血糖波动对2型糖尿病急性冠状动脉综合征(ACS)患者急性期血管生成素2(angiopoietin-2,Ang-2)与内质网应激的变化及对ACS危险性的影响.方法 连续入选78例糖尿病合并ACS患者,ACS病程＜7 d.并选择78例无AGS的糖尿病患者作对照,用全球急性冠状动脉事件(GRACE)评分评估ACS患者危险度;采用动态血糖检测系统(CGMS)进行3d的血糖监测;分别用实时PCR和Western印迹法检测Ang-2、内质网应激相关基因重链结合蛋白(Bip)、肌醇需求蛋白激酶Ⅰ(IREI)、类PKR的内质网应激酶(PERK)、氧调节蛋白150(ORP150)、转录激活因子6(ATF6)、X盒结合蛋白1(XBP1)、磷酸化的真核翻译起始因子2α(p-eIF2α)和单核细胞趋化蛋白1(MCP-1)mRNA和蛋白表达变化;对2组间参数进行比较;同时将血糖波动参数与Ang-2内质网应激相关基因和MCP-1也进行相关性分析;将血糖波动参数、Ang-2和内质网应激相关基因与GRACE评分进行相关分析.结果 (1)ACS组的日平均血糖波动幅度(MA GE)、日间血糖平均绝对差(MODD)、平均餐后血糖波动幅度(MPPGE)和最大血糖波动幅度(LAGE)明显高于对照组(均P＜0.05).(2)ACS组Ang-2、内质网相关基因Bip、IREI、PERK、ORP150、ATF6、XBP1、p-eIF2α和MCP-1 mRNA表达量与对照组比较均有统计学差异(均P＜0.05).(3)在ACS组中,作pearson相关分析,Ang-2与MAGE、LAGE、MPPGE相关(r=0.432、0.279、0.386,均P＜0.05),Bip与MAGE、LAGE、MPPGE相关(r=0.783、0.589、0.887,均P＜0.05);IREI与MAGE、LAGE、MPPGE、MODD相关(r=0.567、0.783、0.569、0.823,均P＜0.05);PERK与MAGE、MPPGE、MODD相关(r=0.687、0.902、0.709,均P＜0.05);ORP150与MAGE、LAGE、MPPGE、MODD相关(r=0.779、0.871、0.775、0.689,均P＜0.05);ATF6与MAGE、LAGE、MPPGE、MODD相关(r=0.873、0.675、0.893、0.884,均P＜0.05),而XBP1与血糖波动无相关性(P＞0.05).(4)内质网应激相关基因、MCP-1与血糖波动参数相关.(5)多元Logistic逐步回归分析血糖波动是内质网应激相关基因、Ang-2和GRACE的危险因素,LAGE、MPPGE、Bip、IREI、PERK、ORP150、ATF6是影响Ang-2的危险因素;而Ang-2、年龄、MAGE、稳态模型评估的胰岛素抵抗指数(HOMA-IR)、Bip、ATF6是影响GRACE的危险因素.(6) ACS患者射血分数水平与MAGE、LAGE均呈负相关性,多元线性回归分析显示年龄、HOMA-IR、Ang-2、和MAGE、Bip、ATF6可与射血分数建立线性回归关系.结论 血糖波动使得Ang-2升高和导致内质网应激增加,还可能与心脏收缩功能受损有关.增加了患者的危险度,并影响了2型糖尿病合并ACS患者的预后.
目的 探討血糖波動對2型糖尿病急性冠狀動脈綜閤徵(ACS)患者急性期血管生成素2(angiopoietin-2,Ang-2)與內質網應激的變化及對ACS危險性的影響.方法 連續入選78例糖尿病閤併ACS患者,ACS病程＜7 d.併選擇78例無AGS的糖尿病患者作對照,用全毬急性冠狀動脈事件(GRACE)評分評估ACS患者危險度;採用動態血糖檢測繫統(CGMS)進行3d的血糖鑑測;分彆用實時PCR和Western印跡法檢測Ang-2、內質網應激相關基因重鏈結閤蛋白(Bip)、肌醇需求蛋白激酶Ⅰ(IREI)、類PKR的內質網應激酶(PERK)、氧調節蛋白150(ORP150)、轉錄激活因子6(ATF6)、X盒結閤蛋白1(XBP1)、燐痠化的真覈翻譯起始因子2α(p-eIF2α)和單覈細胞趨化蛋白1(MCP-1)mRNA和蛋白錶達變化;對2組間參數進行比較;同時將血糖波動參數與Ang-2內質網應激相關基因和MCP-1也進行相關性分析;將血糖波動參數、Ang-2和內質網應激相關基因與GRACE評分進行相關分析.結果 (1)ACS組的日平均血糖波動幅度(MA GE)、日間血糖平均絕對差(MODD)、平均餐後血糖波動幅度(MPPGE)和最大血糖波動幅度(LAGE)明顯高于對照組(均P＜0.05).(2)ACS組Ang-2、內質網相關基因Bip、IREI、PERK、ORP150、ATF6、XBP1、p-eIF2α和MCP-1 mRNA錶達量與對照組比較均有統計學差異(均P＜0.05).(3)在ACS組中,作pearson相關分析,Ang-2與MAGE、LAGE、MPPGE相關(r=0.432、0.279、0.386,均P＜0.05),Bip與MAGE、LAGE、MPPGE相關(r=0.783、0.589、0.887,均P＜0.05);IREI與MAGE、LAGE、MPPGE、MODD相關(r=0.567、0.783、0.569、0.823,均P＜0.05);PERK與MAGE、MPPGE、MODD相關(r=0.687、0.902、0.709,均P＜0.05);ORP150與MAGE、LAGE、MPPGE、MODD相關(r=0.779、0.871、0.775、0.689,均P＜0.05);ATF6與MAGE、LAGE、MPPGE、MODD相關(r=0.873、0.675、0.893、0.884,均P＜0.05),而XBP1與血糖波動無相關性(P＞0.05).(4)內質網應激相關基因、MCP-1與血糖波動參數相關.(5)多元Logistic逐步迴歸分析血糖波動是內質網應激相關基因、Ang-2和GRACE的危險因素,LAGE、MPPGE、Bip、IREI、PERK、ORP150、ATF6是影響Ang-2的危險因素;而Ang-2、年齡、MAGE、穩態模型評估的胰島素牴抗指數(HOMA-IR)、Bip、ATF6是影響GRACE的危險因素.(6) ACS患者射血分數水平與MAGE、LAGE均呈負相關性,多元線性迴歸分析顯示年齡、HOMA-IR、Ang-2、和MAGE、Bip、ATF6可與射血分數建立線性迴歸關繫.結論 血糖波動使得Ang-2升高和導緻內質網應激增加,還可能與心髒收縮功能受損有關.增加瞭患者的危險度,併影響瞭2型糖尿病閤併ACS患者的預後.
목적 탐토혈당파동대2형당뇨병급성관상동맥종합정(ACS)환자급성기혈관생성소2(angiopoietin-2,Ang-2)여내질망응격적변화급대ACS위험성적영향.방법 련속입선78례당뇨병합병ACS환자,ACS병정＜7 d.병선택78례무AGS적당뇨병환자작대조,용전구급성관상동맥사건(GRACE)평분평고ACS환자위험도;채용동태혈당검측계통(CGMS)진행3d적혈당감측;분별용실시PCR화Western인적법검측Ang-2、내질망응격상관기인중련결합단백(Bip)、기순수구단백격매Ⅰ(IREI)、류PKR적내질망응격매(PERK)、양조절단백150(ORP150)、전록격활인자6(ATF6)、X합결합단백1(XBP1)、린산화적진핵번역기시인자2α(p-eIF2α)화단핵세포추화단백1(MCP-1)mRNA화단백표체변화;대2조간삼수진행비교;동시장혈당파동삼수여Ang-2내질망응격상관기인화MCP-1야진행상관성분석;장혈당파동삼수、Ang-2화내질망응격상관기인여GRACE평분진행상관분석.결과 (1)ACS조적일평균혈당파동폭도(MA GE)、일간혈당평균절대차(MODD)、평균찬후혈당파동폭도(MPPGE)화최대혈당파동폭도(LAGE)명현고우대조조(균P＜0.05).(2)ACS조Ang-2、내질망상관기인Bip、IREI、PERK、ORP150、ATF6、XBP1、p-eIF2α화MCP-1 mRNA표체량여대조조비교균유통계학차이(균P＜0.05).(3)재ACS조중,작pearson상관분석,Ang-2여MAGE、LAGE、MPPGE상관(r=0.432、0.279、0.386,균P＜0.05),Bip여MAGE、LAGE、MPPGE상관(r=0.783、0.589、0.887,균P＜0.05);IREI여MAGE、LAGE、MPPGE、MODD상관(r=0.567、0.783、0.569、0.823,균P＜0.05);PERK여MAGE、MPPGE、MODD상관(r=0.687、0.902、0.709,균P＜0.05);ORP150여MAGE、LAGE、MPPGE、MODD상관(r=0.779、0.871、0.775、0.689,균P＜0.05);ATF6여MAGE、LAGE、MPPGE、MODD상관(r=0.873、0.675、0.893、0.884,균P＜0.05),이XBP1여혈당파동무상관성(P＞0.05).(4)내질망응격상관기인、MCP-1여혈당파동삼수상관.(5)다원Logistic축보회귀분석혈당파동시내질망응격상관기인、Ang-2화GRACE적위험인소,LAGE、MPPGE、Bip、IREI、PERK、ORP150、ATF6시영향Ang-2적위험인소;이Ang-2、년령、MAGE、은태모형평고적이도소저항지수(HOMA-IR)、Bip、ATF6시영향GRACE적위험인소.(6) ACS환자사혈분수수평여MAGE、LAGE균정부상관성,다원선성회귀분석현시년령、HOMA-IR、Ang-2、화MAGE、Bip、ATF6가여사혈분수건립선성회귀관계.결론 혈당파동사득Ang-2승고화도치내질망응격증가,환가능여심장수축공능수손유관.증가료환자적위험도,병영향료2형당뇨병합병ACS환자적예후.
Objective To investigate the changes in angiopoietin 2 and endoplasmic reticulum stress,and the prognosis of acute phase of coronary syndrome (ACS) in type 2 diabetic patients with glycemic fluctuations.Methods Seventy-eight cases of consecutive diabetic patients with ACS within 7 days were enrolled.Another 78 cases of non-diabetic patients with ACS were selected as control.Risk assessment with global acute coronary events (GRACE) score in patients with ACS,dynamic blood glucose monitoring system (CGMS) for three days,realtime PCR analysis of angiopoietin-2,within the reticulum stress-related heavy chain binding protein (Bip),inositol kinase demand Ⅰ (IREI),endoplasmic reticulum class should PKR kinase (PERK),oxygen-regulated protein 150 (ORP150),activating transcription factor 6 (ATF6),X-box binding protein 1 (XBP1)mRNA expression change,phosphorylation of eukaryotic translation initiation factor 2oα (p-eIF2α) by western blotting angiopoietin-2,parameters were compared between the two groups.Correlation analysis with GRACE score ; while angiopoietin-2 parameters and glycemic fluctuation,endoplasmic reticulum stress-related genes correlation analysis were made.Results (1) ACS group average daily blood glucose fluctuations(MAGE),mean absolute difference daytime blood glucose (MODD),and postprandial blood glucose fluctuation (MPPGE) and the maximum amplitude of glycemic excursions (LAGE) were significantly higher [MAGE(5.13 ± 1.19) vs (3.19 ± 0.55) mmol/L,MODD (2.59 ± 0.72) vs (1.72 ± 0.63) mmol/L; MPPGE (3.51 ± 1.01) vs (2.58 ± 0.55) mmol/L and LAGE (7.75 ± 2.39) vs (4.34 ± 0.85) mmol/L,all P＜0.05].(2)In ACS group angiopoietin-2,endoplasmic reticulum associated genes Bip,IREI,PERK,ORP150,ATF6,XBP1,and monocyte chemoattractant protein 1 (MCP-1) mRNA expression levels as compared with the control group were statistically significant(all P＜0.05) ; Angiopoietin-2,protein p-eIF2α were higher(P＜0.05).(3) In the ACS group with pearson correlation analysis,angiopoietin-2 and MAGE,LAGE,MPPGE correlation (r =0.432,0.279,0.386,all P＜0.05),Bip and MAGE,LAGE,MPPGE correlation(r =0.783,0.589,0.887,all P＜ 0.05) ; IREI and MAGE,LAGE,MPPGE,MODD correlation (r =0.567,0.783,0.569,0.823,all P＜0.05) ; PERK and MAGE,MPPGE,MODD correlation(r =0.687,0.902,0.709,all P＜0.05) ; ORP150 and MAGE,LAGE,MPPGE,MODD correlation(r=0.779,0.871,0.775,0.689,all P＜0.05) ; ATF6 and MAGE,LAGE,MPPGE,MODD correlation(r =0.873,0.675,0.893,0.884,all P＜0.05),while XBP1 with no correlation with glycemic fluctuations (P＞0.05).(4) The endoplasmic reticulum stress gene was related to MCP-1 and blood glucose fluctuation parameters.(5) Multiple Logistic regression analysis revealed that LAGE,MPPGE,Bip,IREI,PERK,ORP150,ATF6 were risk factors affecting angiopoietin-2,and angiopoietin-2,ages,MAGE,homeostasis model assessment for insulin resistance,Bip,ATF6 were risk factors affecting GRACE.(6) The ejection fractions of the ACS patients showed negative correlation with MAGE and LAGE,multiple linear regression analysis showed that age,HOMA-IR,Ang-2,and MAGE,Bip,ATF6 established the linear regression relation with ejection fraction.Conclusion Glycemic fluctuations cause angiopoietin-2 to rise and lead to increased endoplasmic reticulum stress and affect the prognosis of diabetic patients with ACS.
