CAJ | 학술논문

目的了解不同病程、不同达标情况下2型糖尿病患者血管内皮功能的差异及机制,并探讨过氧化物酶体增殖物激活受体γ辅助激活子α(peroxisome proliferator-activated receptor-γ coactivator 1 α,PGC-1α)对糖尿病大血管的保护作用.方法招募正常糖耐量者94名、糖耐量受损患者87例及2型糖尿病患者306例.通过高分辨率彩色多普勒测定肱动脉内皮依赖的血流介导的血管扩张率(flow-mediatedvasodilatation,FMD)、硝酸甘油介导的非内皮依赖的血管扩张率(glyceryl trinitrate dilatation,GTN)、颈动脉内膜中层厚度(carotid intima-media thickness,CIMT),并进行相关性分析.采用硝酸还原酶法测量NO,Western印迹法检测丝氨酸苏氨酸激酶473位点丝氨酸残基(Akt-Ser473)磷酸化水平,逆转录荧光定量实时PCR法检测研究对象外周血单个核细胞IL-β mRNA和PGC-1α mRNA转录水平.结果 FMD值在新诊断2型糖尿病组已明显低于正常糖耐量组和糖耐量受损组(P＜0.01),而GTN和CIMT尚未出现差异.糖尿病组PGC-1α mRNA转录水平显著低于非糖尿病组(P＜0.01).相关性分析显示PGC-1α与FMD、GTN正相关(P＜0.05或P＜0.01).Logistic多元回归分析显示,在校正其他影响因素之后,PGC-1α与FMD独立相关(P＜0.01).结论 FMD是敏感的糖尿病大血管并发症早期预警指标,而CIMT、GTN更侧重于并发症的进展；PGC-1α对糖尿病大血管的保护可能存在内皮依赖和内皮非依赖两种机制.
목적 료해불동병정、불동체표정황하2형당뇨병환자혈관내피공능적차이급궤제,병탐토과양화물매체증식물격활수체γ보조격활자α(peroxisome proliferator-activated receptor-γ coactivator 1 α,PGC-1α)대당뇨병대혈관적보호작용.방법 초모정상당내량자94명、당내량수손환자87례급2형당뇨병환자306례.통과고분변솔채색다보륵측정굉동맥내피의뢰적혈류개도적혈관확장솔(flow-mediatedvasodilatation,FMD)、초산감유개도적비내피의뢰적혈관확장솔(glyceryl trinitrate dilatation,GTN)、경동맥내막중층후도(carotid intima-media thickness,CIMT),병진행상관성분석.채용초산환원매법측량NO,Western인적법검측사안산소안산격매473위점사안산잔기(Akt-Ser473)린산화수평,역전록형광정량실시PCR법검측연구대상외주혈단개핵세포IL-β mRNA화PGC-1α mRNA전록수평.결과 FMD치재신진단2형당뇨병조이명현저우정상당내량조화당내량수손조(P＜0.01),이GTN화CIMT상미출현차이.당뇨병조PGC-1α mRNA전록수평현저저우비당뇨병조(P＜0.01).상관성분석현시PGC-1α여FMD、GTN정상관(P＜0.05혹P＜0.01).Logistic다원회귀분석현시,재교정기타영향인소지후,PGC-1α여FMD독립상관(P＜0.01).결론 FMD시민감적당뇨병대혈관병발증조기예경지표,이CIMT、GTN경측중우병발증적진전；PGC-1α대당뇨병대혈관적보호가능존재내피의뢰화내피비의뢰량충궤제.
Objective To explore the vascular endothelial function in individuals with normal glucose tolerance (NGT),impaired glucose tolerance (IGT),and type 2 diabetes mellitus,and to study the role played by PPARγcoactivator 1 α (PGC-1 α) in diabetic macrovascular function.Methods A total of 94 subjects with NGT,87with IGT,and 306 with type 2 diabetes mellitus were recruited in the study.Carotid flow-mediated vasodilatation (FMD),glyceryl trinitrate dilatation (GTN),and carotid intima-media thickness (CIMT) were assessed by highresolution B-mode color vascular Doppler instrument.Finally,correlation analysis was conducted.NO,Akt-Ser473phosphorylation levels,IL-β,and PGC-1 α mRNA expression levels were measured by means of nitrate reductase,western blot,and reverse transcriptase real-time fluorescence quantitative PCR assay methods in peripheral blood mononuclear cells respectively.Results FMD in newly-diagnosed type 2 diabetic group was significantly lower than that in NGT and IGT groups(P＜0.01).GTN and CIMT showed no difference.PGC-1 α mRNA transcription level in diabetic group was significantly lower than that in non-diabetic groups (P＜0.01).Correlation analysis showed that PGC-1 α was positively correlated with FMD and GTN (P＜0.05 or P＜0.01).Logistic regression analysis revealed that PGC-1 α was independently associated with FMD (P ＜ 0.01) after adjusting other influencing factors.Conclusion FMD is a more sensitive early warning indicator of endothelial function than CIMT and GTN.As indices of atherosclerosis,CIMT and GTN are more or less focused on the progression of macrovascular complications.PGC-1 α is a protective factor of macro-vasculature in diabetes mellitus,and its effect may be achieved through the protection of the vascular endothelium.