巴马司他对高血压小鼠模型血压及血清基质金属蛋白酶9水平的影响

Effect of batimastat on hypertension mice and its serum matrix metalloproteinase

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 pressure,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 Ob,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.Results（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 drop,the differences were statistically significant（P〈 0.05,P 〈0.01）;compared with control group and low dose sub group,high dose groups 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 decreased with the increase of drug action time,differences were statistical significance（P〈0.05,P〈0.01）;paired compassion 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.