巴马司他对高血压小鼠血清中MMP9的影响

Effect of bamazepril on serum MMP9 level in hypertensive mice

目的探讨外源性基质金属蛋白酶9(matrix metalloproteinase 9,MMP9)抑制剂巴马司他对高血压小鼠血清中MMP9水平和活性的影响。方法应用酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)和RT-PCR法,分别检测高血压小鼠和正常小鼠血清中MMP9及其mRNA水平;将36例高血压小鼠平均分为3组,连续3天分别以高剂量巴马司他(30 mg/kg)、低剂量巴马司他(10 mg/kg)和生理盐水对小鼠腹腔进行注射,依次在最后一次注射后0 h、2 h、4 h、6 h对各组小鼠血清中MMP9及其mRNA水平进行检测;应用明胶酶谱法检测各组小鼠血清中MMP9活性。结果血清中MMP9及其mRNA水平随着巴马司他剂量及药物作用时间的增加逐渐接近于正常水平;MMP9活性随着巴马司他剂量的增加逐渐下降;高剂量巴马司他能够显著降低高血压小鼠的血压水平(P<0.05)。结论巴马司他能够降低高血压小鼠血压水平及其血清中MMP9水平和活性。

Objective To explore the effect of bamazepril on serum matrix metalloproteinase 9 （MMP9） level in hypertensive mice. Methods The level of MMP9 mRNA and MMP9 in serum of hypertension and nor-mal mice were assayed by enzyme linked immunosorbent assay （ELISA） and RT-PCR. Then the hypertension mice were divided into 3 groups （12 per group）. The frst two groups received daily administration of intraperi-toneal injection of high-dose （30 mg/kg） and low-dose （10 mg/kg） batimastat for 3 d, while the third group was injected by 0.9% saline instead. The levels of MMP9 mRNA and MMP9 in serum were detected after the last injection by 0 h, 2 h, 4 h, 6 h, in turns. The activity of MMP9 was assessed by gelatin zymography. Results The average levels of MMP9 mRNA and MMP9 in serum of hypertension mice were gradually close to normal with the increasing action time and dose of batimastat. The activity of MMP9 in serum was declined with the increas-ing of batimastat. In addition, high-dose batimastat could signifcantly reduce the blood pressure of hypertension mice （P〈0.05）. Conclusion Batimastat can reduce the blood pressure of hypertension mice, as well as decrease the level and activity of MMP9 in serum of hypertension mice.