中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2015年
15期
1179-1183
,共5页
王静%戴琳%于鲁欣%孙艺铸
王靜%戴琳%于魯訢%孫藝鑄
왕정%대림%우로흔%손예주
脓毒症%过氧化物酶体类%内皮,血管%增殖物激活受体-γ
膿毒癥%過氧化物酶體類%內皮,血管%增殖物激活受體-γ
농독증%과양화물매체류%내피,혈관%증식물격활수체-γ
Sepsis%Peroxisomes%Endothelial,vascular%Proliferator activated receptor-γ
目的 探讨过氧化物酶体增殖物激活受体-γ(PPAR-γ)人工合成配体罗格列酮(ROSI)对脂多糖(LPS)诱导的脓毒症大鼠内皮损伤的作用.方法 健康雄性SD大鼠40只,随机分为4组(每组10只):正常对照组;LPS刺激组;罗格列酮(ROSI)预处理组;选择性拮抗剂2-氯-5-硝基苯胺(GW9662)预处理组.在每组操作结束后4h取血.免疫细胞化学结合图像分析法检测外周血单个核细胞(PBMC)内PPAR-γ的表达活性.内皮损伤标志物包括血管细胞黏附分子(VCAM-1)、细胞间黏附分子(ICAM-1)、血管生成素-2(Ang-2)、血栓调节蛋白(TM)、抗凝血酶-Ⅲ(AT-Ⅲ)、组织因子(TF)、vWF因子(vWF)和循环内皮细胞(CEC).结果 ROSI组PPAR-γ表达与LPS刺激组比较显著增加(111.0 ±4.1,P＜1.01).GW9662组PPAR-γ表达显著降低,与正常组比较差异无统计学意义(44.2 ±264.0,P＞1.05).VEC诱导的VCAM-1、ICAM-1、Ang-2、TM、AT-Ⅲ、TF、vWF在LPS组明显升高,与正常对照组比较差异有统计学意义(P＜0.01).ROSI预处理则大大减轻了这些指标的升高,与LPS组比较差异有统计学意义(P＜0.01).GW9662预处理组与LPS组比较差异无统计学意义(P＞0.05).反映VEC凋亡的标志物外周血CEC数量在LPS组明显升高,与正常对照组比较差异有统计学意义(P＜0.01).ROSI预处理则大大减轻了CEC数量的升高,与LPS组比较差异有统计学意义(P＜0.01).GW9662预处理组与LPS组比较差异无统计学意义[(5.2±0.8)个/μl比(5.7±0.6)个/μl,P＞1.05].结论 过氧化物酶体增殖物激活受体-γ激动剂能够改善脓毒症导致的内皮损伤,其机制可能与其稳定血管内皮细胞,改善严重炎症反应和凝血功能紊乱有关.
目的 探討過氧化物酶體增殖物激活受體-γ(PPAR-γ)人工閤成配體囉格列酮(ROSI)對脂多糖(LPS)誘導的膿毒癥大鼠內皮損傷的作用.方法 健康雄性SD大鼠40隻,隨機分為4組(每組10隻):正常對照組;LPS刺激組;囉格列酮(ROSI)預處理組;選擇性拮抗劑2-氯-5-硝基苯胺(GW9662)預處理組.在每組操作結束後4h取血.免疫細胞化學結閤圖像分析法檢測外週血單箇覈細胞(PBMC)內PPAR-γ的錶達活性.內皮損傷標誌物包括血管細胞黏附分子(VCAM-1)、細胞間黏附分子(ICAM-1)、血管生成素-2(Ang-2)、血栓調節蛋白(TM)、抗凝血酶-Ⅲ(AT-Ⅲ)、組織因子(TF)、vWF因子(vWF)和循環內皮細胞(CEC).結果 ROSI組PPAR-γ錶達與LPS刺激組比較顯著增加(111.0 ±4.1,P＜1.01).GW9662組PPAR-γ錶達顯著降低,與正常組比較差異無統計學意義(44.2 ±264.0,P＞1.05).VEC誘導的VCAM-1、ICAM-1、Ang-2、TM、AT-Ⅲ、TF、vWF在LPS組明顯升高,與正常對照組比較差異有統計學意義(P＜0.01).ROSI預處理則大大減輕瞭這些指標的升高,與LPS組比較差異有統計學意義(P＜0.01).GW9662預處理組與LPS組比較差異無統計學意義(P＞0.05).反映VEC凋亡的標誌物外週血CEC數量在LPS組明顯升高,與正常對照組比較差異有統計學意義(P＜0.01).ROSI預處理則大大減輕瞭CEC數量的升高,與LPS組比較差異有統計學意義(P＜0.01).GW9662預處理組與LPS組比較差異無統計學意義[(5.2±0.8)箇/μl比(5.7±0.6)箇/μl,P＞1.05].結論 過氧化物酶體增殖物激活受體-γ激動劑能夠改善膿毒癥導緻的內皮損傷,其機製可能與其穩定血管內皮細胞,改善嚴重炎癥反應和凝血功能紊亂有關.
목적 탐토과양화물매체증식물격활수체-γ(PPAR-γ)인공합성배체라격렬동(ROSI)대지다당(LPS)유도적농독증대서내피손상적작용.방법 건강웅성SD대서40지,수궤분위4조(매조10지):정상대조조;LPS자격조;라격렬동(ROSI)예처리조;선택성길항제2-록-5-초기분알(GW9662)예처리조.재매조조작결속후4h취혈.면역세포화학결합도상분석법검측외주혈단개핵세포(PBMC)내PPAR-γ적표체활성.내피손상표지물포괄혈관세포점부분자(VCAM-1)、세포간점부분자(ICAM-1)、혈관생성소-2(Ang-2)、혈전조절단백(TM)、항응혈매-Ⅲ(AT-Ⅲ)、조직인자(TF)、vWF인자(vWF)화순배내피세포(CEC).결과 ROSI조PPAR-γ표체여LPS자격조비교현저증가(111.0 ±4.1,P＜1.01).GW9662조PPAR-γ표체현저강저,여정상조비교차이무통계학의의(44.2 ±264.0,P＞1.05).VEC유도적VCAM-1、ICAM-1、Ang-2、TM、AT-Ⅲ、TF、vWF재LPS조명현승고,여정상대조조비교차이유통계학의의(P＜0.01).ROSI예처리칙대대감경료저사지표적승고,여LPS조비교차이유통계학의의(P＜0.01).GW9662예처리조여LPS조비교차이무통계학의의(P＞0.05).반영VEC조망적표지물외주혈CEC수량재LPS조명현승고,여정상대조조비교차이유통계학의의(P＜0.01).ROSI예처리칙대대감경료CEC수량적승고,여LPS조비교차이유통계학의의(P＜0.01).GW9662예처리조여LPS조비교차이무통계학의의[(5.2±0.8)개/μl비(5.7±0.6)개/μl,P＞1.05].결론 과양화물매체증식물격활수체-γ격동제능구개선농독증도치적내피손상,기궤제가능여기은정혈관내피세포,개선엄중염증반응화응혈공능문란유관.
Objective To explore the effects of rosiglitazone,a synthetic Iigand of proliferator-activated receptor-γ (PPAR-γ) on vascular endothelial injuries in septic rats.Methods A total of 40 male Sprague-Dawley rats were randomly divided into 4 groups of vehicle control,lipopolysaccharide (LPS),pretreatment of rosiglitazone (ROSI) and pretreatment of PPAR-γ antagonist 2-chloro-5-nitroaniline (GW9662) (n =10 each).At 4 hours post-intervention,blood samples were collected to detect the expression of PPAR-γby immunocytochemistry and image analysis.And the following parameters of vascular endothelial injury were measured:Vascular cell adhesion molecule-1 (VCAM-1),intercellular adhesion molecule-1 (ICAM-1),angiopoietin-2 (Ang-2),thrombomodulin (TM),anti-thrombin Ⅲ (AT-Ⅲ),tissue factor (TF),von Willebrand factor (vWF) and circulating endothelial cell (CEC).Results ① In ROSI group,the expression of PPAR-γ was significantly higher than that in LPS group (P ＜ 0.01).In GW9662 group,the expression of PPAR-γ had no significant difference compared to vehicle control group (P ＞0.05).② The serum concentrations of VCAM-1,ICAM-1,Ang-2,TM,AT-Ⅲ,TF and vWF were significantly higher in LPS group than those in vehicle control group (P ＜ 0.01).The concentrations of these parameters in ROSI group were significantly lower than those in LPS group (P ＜ 1.01).In GW9662 group,the concentrations of these parameters had no significant difference compared with LPS group (P ＞ 0.05).③The numbers of CEC were significantly higher in LPS group than those in vehicle control group (P ＜ 0.01).And the numbers of CEC were significantly lower in ROSI group than those in LPS group (P ＜ 0.01).In GW9662 group,the numbers of CEC had no significant difference compared with LPS group (P ＞ 0.05).Conclusion Proliferator-activated receptor-γ agonist improves sepsis-induced vascular endothelial injury.And its mechanism may be through stabilizing vascular endothelial cell for improving serious inflammatory reaction and blood coagulation dysfunction.
