血红素加氧酶-1上调自发性高血压大鼠肝脏MMP-2与MMP-9表达

摘要

Objective To explore the effects of hemeoxygenase-1 (HO-1) induction on matrix metalloproteinase 2 (MMP-2) and MMP-9 expression in liver of spontaneously hypertensive rats (SHR).Methods Rats were randomly divided into 4 groups.Wistar induction group (WH) and SHR induction group (SH):8 g/L hemin was administered to the animals intraperitoneally at a concentration of 15 mg/kg · d for 4 consecutive days to induce expression of HO-1 ; Wistar control group (W) and SHR control group (S):equal volume of 0.1 mol/L NaOH (pH 8.3) was administered intraperitoneally as controls.Systolic blood pressure (BP) of rats was determined.The expressions of HO-1,MMP-2 and MMP-9 in liver were determined by immunohistochemistry.The relative activity of MMP-2 and MMP-9 in plasma were detected by gelatin zymography.Results The expression of liver HO-1,MMP-2 and MMP-9 was significantly higher in WH and SH group as compared with W and S group,respectively(P ＜ 0.01).Induction of HO-1 significantly attenuated BP of SHR.The relative activity of MMP-2 and MMP-9 in rat plasma was significantly higher in S group as compared with W group (P ＜0.01).The relative activity of MMP-2 and MMP-9 in rat plasma was significantly higher in WH and SH group compared with W and S group,respectively(P ＜ 0.01).Conclusions HO-1 up-regulates expressions of MMP-2 and MMP-9 in liver of SHR and the mechanisms need to be further elucidated.%目的 探讨血红素加氧酶-1 (HO-1)对自发性高血压大鼠(SHR)肝脏基质金属蛋白酶-2(MMP-2)与-9 (MMP-9)表达的影响.方法 大鼠随机分为4组:Wistar诱导组(WH)与SHR诱导组(SH)按15 mg/kg每天连续4天腹腔内注射浓度为8 g/L的氯化血红素(hemin)诱导HO-1表达;Wistar对照组(W)与SHR对照组(S)腹腔内注射等体积0.1 mol/L NaOH (pH8.3).检测大鼠尾动脉收缩压.免疫组化法分析肝脏HO-1及MMPs表达.明胶酶谱法检测血浆MMP-2及MMP-9的相对活性.结果 WH组与SH组肝脏HO-1、MMP-2与MMP-9表达量均显著高于W组与S组.HO-1诱导可显著降低SHR大鼠血压.S组血浆MMP-2及MMP-9相对活性显著高于W组.WH组与SH组血浆MMP-2及MMP-9相对活性显著高于W组与S组.结论 HO-1可上调SHR肝脏MMP-2与MMP-9表达.