目的：探讨外源性基质金属蛋白酶9（MMP-9）抑制剂巴马司他对高血压小鼠血压及其血清中MMP-9水平和活性的影响。方法将36只高血压小鼠（高血压组）平均分为3个亚组，每组12只，连续3 d分别以巴马司他30 mg/kg（高剂量亚组）、10 mg/kg（低剂量亚组）和生理盐水（对照亚组）对小鼠腹腔进行注射，依次在最后1次注射后0 h、2 h、4 h、6 h对各组小鼠血清中MMP-9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MMP-9活性。选择健康小鼠36只为健康对照组，检测血清MMP-9、mRNA水平，并与高血压组比较。结果（1）血压变化：与健康对照组比较，高血压组用药前血压较高，差异有统计学意义（ P ＜0．05），用药后，与对照亚组及低剂量亚组比较，高剂量亚组血压降低，差异均有统计学意义（ P ＜0．05）。（2）血清MMP-9浓度：与健康对照组比较，用药前高血压组MMP-9蛋白浓度显著高（ P ＜0．01），用药后，组内比较：高剂量亚组和低剂量亚组小鼠血清中MMP-9蛋白表达水平均随着药物作用时间的延长而降低，差异均有统计学意义（ P ＜0．05， P ＜0．01）；与低剂量亚组、对照亚组比较，高剂量亚组在2 h、4 h、6 h血清MMP-9浓度均较低，差异均有统计学意义（ P ＜0．05， P ＜0．01）；低剂量亚组与对照亚组比较，2 h、4 h、6 h差异亦均有统计学意义（ P ＜0．05）。（3）MMP-9 mRNA表达：与健康对照组比较，高血压组MMP-9 mRNA水平显著升高（ P ＜0．05）；用药后，高剂量亚组和低剂量亚组小鼠血清中MMP-9 mRNA水平均随着药物作用时间的增加而降低，差异均有统计学意义（ P ＜0．05， P ＜0．01）；对照亚组、低剂量亚组、高剂量亚组两两比较差异均有统计学意义（ P ＜0．05， P ＜0．01）。（4） MMP-9活性测定：随着巴马司他给药剂量的增加，Pro-MMP-9和Active-MMP-9活性呈减弱趋势。结论巴马司他能够降低高血压小鼠血压水平及其血清中MMP-9水平和活性。%Objective To study the effect of matrix metalloproteinase 9 ( MMP-9) inhibitor batimastat on blood pres-sure, serum MMP-9 level and activity in hypertension mice .Methods Thirty-six hypertension ( hypertension group ) mice were divided into 3 groups, with 12 rats in each group, give 3 days of high dose of batimastat (30 mg/kg, high dose group), low dose of batimastat (10 mg/kg, low dose group) and physiological saline (control group) injection on mouse peritoneal in the three groups respectively , the serum levels of MMP-9 and mRNA levels were detected followed in the 1 last after injection 0 h, 2 h, 4 h, 6 h; serum levels of MMP-9 activity were detected by gelatin zymography assay .Select 36 healthy mice as healthy control group , serum levels of MMP-9 and mRNA levels were detected , and compared with hypertension group .Re-sults (1) Blood pressure change:compared with health control group , hypertension group before treatment blood pressure is higher, the difference was statistically significant ( P <0.05), after treatment, compared with the control group and low dose group, high dose group blood pressure decreased , the differences were statistically significant ( P <0.05).(2) The serum concentration of MMP-9: compared with health control group , before treatment , in the hypertension group , MMP-9 protein levels were significantly higher ( P <0.01), after treatment, the within group comparisons:in high dose group and low dose group, the expression of MMP-9 protein in the serum of mice were decreased along with prolonging the time of drugs , the differences were statistically significant ( P <0.05, P <0.01);compared with control group and low dose sub group , high dose group's serum MMP-9 concentration was low at 2 h,4 h,6 h,the differences were statistically significant ( P <0.05, P <0.01);compared between low dose group and control group , 2 h, 4 h, 6 h the difference had statistical significance ( P <0.05).(3) The expression of MMP-9 mRNA: compared with health control group , hypertension group MMP-9 mRNA was elevated ( P <0.05);after treatment, high dose group and low dose group of mice'level of serum MMP-9 mRNA were de-creased with the increase of drug action time , differences were statistical significance ( P <0.05, P <0.01);paired compas-sion of low dose sub group, high dose sub group, control sub group showed significant differences ( P <0.05, P <0.01). (4) Determination of MMP-9 activity:with the batimastat dose increased, Pro MMP-9 and Active MMP-9 activity decreased. Conclusion Batimastat can reduce blood pressure level and serum MMP-9 level and activity of high blood pressure mice .
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