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背景:过氧化体增殖物激活型受体γ可以通过抑制白细胞介素6、环氧合酶、内皮素1、一氧化氮合酶、基质金属蛋白酶9、明胶酶、黏附分子等的表达,抑制心肌肥厚中炎性反应。目的:观察压力负荷所致心肌肥厚过程中,过氧化体增殖物激活型受体γ配体-罗格列酮钠对肥厚心肌中炎性因子的影响。设计:随机对照动物实验。单位:解放军第三军医大学新桥医院心血管外科。材料:纯种S.P.F.级雄性SD大鼠50只,体质量(220±22)g。方法:实验于2004-08/2005-10在解放军第三军医大学野战外科研究所完成。SD大鼠50只随机分为对照组、假手术-生理盐水组、假手术-罗格列酮组、心肌肥厚-生理盐水组、心肌肥厚-罗格列酮组,各10只。采用腹主动脉缩窄法复制压力超负荷大鼠心肌肥厚模型,罗格列酮组:于术后4周用罗格列酮钠生理盐水溶液4mg/(kg·d)腹腔注射1周;生理盐水组:于术后4周用生理盐水腹腔注射1周[1mL/(kg·d)]。术后5周测定心肌肥厚指数及血液动力学指标;放免法检测左心室肌肿瘤坏死因子α、血小板活化因子含量,以及髓过氧化物酶含量;逆转录聚合酶链反应法检测心肌中过氧化体增殖物激活型受体γmRNA的表达;EMSA法检测核因子κB活性。主要观察指标:动物模型大鼠血流动力学和心室重塑指标,心肌炎性指标检测。结果:实验动物50只,对照组中1只在饲养3周后因撕咬外伤造成死亡,49只进入结果分析。①在主动脉缩窄术后心肌肥厚-罗格列酮组肥厚心肌中瘤坏死因子α、血小板活化因子、髓过氧化物酶的含量比心肌肥厚-生理盐水组显著降低(P<0.01～0.05),但仍高于对照组水平(P<0.01)。②心肌肥厚-罗格列酮组、心肌肥厚-生理盐水组心肌组织中过氧化体增殖物激活型受体γmRNA表达均明显高于对照组(P<0.01),且心肌肥厚-罗格列酮组高于心肌肥厚-生理盐水组(P<0.01)。③心肌肥厚-生理盐水组、心肌肥厚-罗格列酮组心肌细胞核因子κB的DNA结合活性明显高于对照组(P<0.01),且心肌肥厚-罗格列酮组明显低于心肌肥厚-生理盐水组(P<0.01)。结论:压力负荷增加引起心肌肥厚,肥厚心肌组织中核因子-κB激活明显增强,肿瘤坏死因子α、PAF、髓过氧化物酶表达升高,这一炎症反应能被过氧化体增殖物激活型受体γ人工合成配体罗格列酮钠所抑制。
BACKGROUND: Peroxisome proliferator-activated receptor γ can inhibit the expression of interleukin-6, cyclooxygenase, endothelin-1, nitric oxide synthase, matrix metalloproteinase 9, gelatinase, adhesion molecule and so on Inflammatory reaction in cardiac hypertrophy. OBJECTIVE: To observe the effect of peroxisome proliferator-activated receptor γ ligand-sodium rosiglitazone on inflammatory cytokines in hypertrophic myocardium during cardiac hypertrophy induced by pressure overload. Design: Randomized controlled animal experiments. SETTING: Cardiovascular Surgery, Xinqiao Hospital, Third Military Medical University. MATERIALS: Fifty pure SD S.P.F. male SD rats weighing 220 ± 22 g were used. METHODS: The experiment was performed at the Institute of Field Surgery, Third Military Medical University of Chinese PLA from August to 2005. Fifty SD rats were randomly divided into control group, sham operation - saline group, sham operation - rosiglitazone group, cardiac hypertrophy - saline group, and cardiac hypertrophy - rosiglitazone group. The model of cardiac hypertrophy was replicated by abdominal aorta in pressure overload rats. The rosiglitazone group was injected intraperitoneally with sodium rosiglitazone 4 mg / (kg · d) for 1 week after 4 weeks of operation. Saline group: intraperitoneal injection of normal saline for 1 week [1 mL / (kg · d)] 4 weeks after the operation. Cardiac hypertrophy index and hemodynamic indexes were measured 5 weeks after operation. Tumor necrosis factor-α, platelet activating factor and myeloperoxidase in left ventricular myocardium were detected by radioimmunoassay. Peroxidation in myocardium was detected by reverse transcription-polymerase chain reaction The expression of γ-actin receptor mRNA was detected by EMSA. The activity of nuclear factor κB was detected by EMSA. MAIN OUTCOME MEASURES: Hemodynamics and ventricular remodeling index, myocarditis index in animal model rats. Results: Fifty experimental animals and one control group died of bite trauma after feeding for three weeks, and 49 animals were involved in the result analysis. ① In hypertrophic myocardium after aortic constriction - the content of tumor necrosis factor-α, platelet activating factor and myeloperoxidase in hypertrophic myocardium of rosiglitazone group was significantly lower than that of cardiac hypertrophy-saline group (P <0.01 ~ 0.05 ), But still higher than the control group (P <0.01). Cardiac hypertrophy-The expression of peroxisome proliferator-activated receptor γmRNA in myocardium of rosiglitazone group and cardiac hypertrophy-saline group were significantly higher than that of the control group (P <0.01), and the cardiac hypertrophy-rosiglitazone Group than in hypertrophy - saline group (P <0.01). Cardiac hypertrophy - saline group, cardiac hypertrophy - The DNA binding activity of nuclear factor kappa B in rosiglitazone group was significantly higher than that in control group (P <0.01), and the cardiac hypertrophy - rosiglitazone group was significantly lower than that of cardiac hypertrophy - Saline group (P <0.01). CONCLUSION: The cardiac hypertrophy is caused by the increase of pressure load. The activation of nuclear factor-κB in hypertrophic myocardium is obviously enhanced. The expression of tumor necrosis factor α, PAF and myeloperoxidase are increased. The inflammatory reaction can be activated by peroxisome proliferator- Inhibition of Body Gamma Synthetic Ligands Sodium.