非诺贝特对大鼠心肌缺血再灌注损伤的保护作用及其机制研究

目的探讨非诺贝特对大鼠心肌缺血再灌注损伤的保护作用及其机制O方法将64只sD大鼠随机分为假手术组、缺血再灌注组、150mg／kg非诺贝特组及300mg／kg非诺贝特组，每组各16只，术前30min分别给予相应处理。采取体内结扎左前降支的方法建立心肌缺血再灌注损伤模型，予酶联免疫吸附法检测大鼠心肌组织中NF-xBp65及IL-6水平，H·E染色观察左一t7室前壁细胞病理形态学改变，并采用Tunel法检测心肌细胞凋亡率。结果假手术组大鼠一t7肌组织中NF-xBp65及IL-6水平、心肌细胞凋亡率分别为（8．11±0．83）pg／mg、（182．67±0．19）pg／mg、（5．09±0．79）％，与其余四组大鼠相比均显著降低（P〈0．05）；与缺血再灌注组比较，非诺贝特组大鼠心肌组织中NF-xBp65及IL-6水平，心肌细胞凋亡率明显降低（P〈0．05），且随着用药剂量的增加而降低，两个不同剂量组比较，差异有统计学意义（P〈0．05）。缺血再灌注组与300mg／kg非诺贝特组中NF-xBp65及IL-6含量水平差异有统计学意义（rl=0．93，r2：0．74，P〈0．01）。结论非诺贝特可通过负性调节NF-xBp65含量水平进而减少IL-6的释放，抑制心肌细胞的凋亡，从而在心肌缺血再灌注损伤中发挥保护作用。

Study of Protection and Mechanisms of Fenofibrate in Rats with Myocardimn Ischemia-reperfusion Injury.

Objective To explore the protection of fenofibrate in rats with myocardium ischemia-reperfusion injury and its mecha- nisms. Methods 64 Sprague-Dawley rats were randomly divided into four groups as sham-operation group, ischemia-reperfusion group, 150 mg/kg fenofibrate group and 300 mg/kg-fenofibrate group, with 16 rats in each group. Relevant treatments were given to rats 30 min before myocardium ischemia operation respectively. A rat model of left anterior descending coronary artery was hgated for 45 min and reperfused for 45 min to establish the model of ischemia-reperfusion. Enzyme linked immunosorbent assay （ELISA） was respectively used to detect levels of NF-kB I065 and IL-6 in myocardium tissue; H·E staining is used to observe morphologic changes of myocardium cells in ischemia/reperfusion injury region. Tunel staining was used to detect cardiac myocyte apeptosis rate （CMAR）. Results The levels of NF-kB 1065, IL-6 and CMAR in sham-operation group were （8.11 ± 0.83）pg/mg, （182.67 ± O. 19）pg/mg and 0.79% respectively, which were significantly decreased compared with the other four groups （ P 〈 0.05）. Com- pared with ischemia-reperfusion group, the levels of NF-kB 1365 and IL-6, CMAR were significantly decreased in fenofibrate group （ P 〈 0.05） ; and they were significantly lower in 300mg/kg-fenofibrate group compared with 150 mg/kg-fenofibrate group （ P 〈 0.05）. The levels of IL-6 and NF-kB p65 in ischemia-reperfusion group and 300mg/kg-fenofibrate group were positively correlated （ r1 = 0. 93, r2 = 0.74, P 〈 0.01）. Conclusions Fenofibrate may reduce the release of IL-6 through down-regulating NF-kB Io65 levels, and prevent myocardium cell apoptosis, and eventually provide protection from ischemia/reperfusion injury.