非诺贝特在急性心肌缺血性损伤中的作用及机制探讨

目的探讨过氧化物酶体增殖物激活受体α（PPARα）配体非诺贝特在急性心肌缺血性损伤中的作用及其机制。方法48只雄性SD大鼠随机均分为3组：对照组和异丙肾上腺素（ISO）模型组接受生理盐水20ml／kg灌胃7日，每日一次；非诺贝特（FF）预处理组接受FF 40mg／kg生理盐水溶液灌胃7日，每日一次。最后一次灌胃后ISO组和FF组接受ISO 5mg／kg腹腔注射。24h后摘眼球取血。硝酸还原酶法测定血清中一氧化氮（NO）含量，双抗体夹心ABC—ELISA法测定血清中肿瘤坏死因子-α（TNF-α）。SDS—PAGE测定心肌组织PPARα蛋白质。取血后处死动物，迅速取出心脏进行病理学检查。测定梗死面积，计算心脏湿重／体重（HW／BW）和梗死范围占心室重的百分比（IS／Vw）。结果ISO组的HW／BW为（6．71±0．55）mg／g，显著高于对照组（4．05±0．37）mg／g，P〈0．01]，FF组的HW/BW为（5．28±0．49）mg／g，显著低于ISO组（P〈0．05），但仍显著高于对照组（P〈0．05）。ISO组的IS／vW为（0．75±0．09）％，显著高于对照组（0．07±0．02）％，P〈0．01]；FF组的IS/VW为（0.31±0.08）％，显著低于ISO组（P〈0．01），但仍显著高于对照组fP〈0．01）。ISO组的血清NO水平为（20．79＋5．95）μmol／L，显著低于对照组（49．65±6．97）μmol／L，P〈0．01]；FF组的NO水平为（80．45±11．61）μmol／L，显著高于对照组和ISS组（均P〈0．01）。ISO组血清TNF-α水平为（275．41±27．61）％，显著高于对照组（20．01±3．29）％，P〈0．01]；FF组血清TNF-α水平为（149．07±22．39）％，显著低于ISO组（P〈0．01），但仍显著高于对照组（P〈0．01）。ISO组心肌PPARα蛋白质表达水平显著低于对照组（P〈0．05）；而FF组的心肌PPARα蛋白质表达水平显著高于对照组和ISO组（均P〈0．05）。结论非诺贝特预处理可通过激活PPARα从而减少?

Effects of fenofibrate on acute myocardial ischemic damage induced by isoproterenol: experiment with rats

Objective To investigate the effects of fenofibrate （FF）, a peroxisome proliferator-activator receptor α （PPAR-α） activator on the cardiac injury caused by myocardial ischemia and mechanism thereof. Methods Forty-eight male SD rats were randomly divided into 3 equal groups： isoprαerenol （ISO） group and control group bαh undergoing gastric lavage of normal saline （NS） 20 ml/kg once a day for 7d, and FF pretreatment group, undergoing gastric lavage of FF solved in NS 20 ml/kg once a day for 7d.One hour after the last lavage the FF and ISO groups underwent intraperitoneal injection of ISO 5 mg/kg, and the control group underwent intrapeitoneal injection of NS. 24 h later blood samples was obtained by picking out the eyeball to isolate serum. And then the hearts were taken out for measurement of heart weight （HW）, pathology of the myocardium, and calculation of the HW/body weight （BW）% and infarction size （IS）/ventricular weight （VW）%. Nitrate reductase method and double antibody sandwich ELISA were used to detect the serum nitrogen oxide （NO） and tumor necrosis factor （ TNF）-α. Sodium dodecyl sulfate polyacrylamide gel electrophoresis was used to examine the PPARα prαein expression in the myocardium. Results The HW/BW of the ISO group was （6.71±0.55） mg/g, significantly higher than that of the control group （4.05±0.37） mg/g, P〈0.01], and the HW/BW of the FF group was （5.28±0.49） mg/g, significantly lower than that of the ISO group （P 〈0.05） and still significantly higher than that of the control group （P 〈0.05）. The IS/VW% of the ISO group was （0.75±0.09）%, significantly higher than that of the control group （0.07±0.02）%, P 〈0.01]; and the IS/VW% of the FF group was （0.31±0.08）%, significantly lower than that of the ISO group （P 〈0.01） and still significantly higher than that of the control group （P 〈0.01）. The serum NO level of the ISO group was （20.79±5.95） μmol/L, significantly lower than that of the