基质金属蛋白酶-9在自发性高血压大鼠心室重构的变化及γ-干扰素的干预研究

Effect of IFN-γ on the expression of Matrix Metalloproteinase-9 and ventriculer remodeling in spontaneously rats

目的:观察基质金属蛋白酶-9(MMP-9)在自发性高血压大鼠心室重构(SHR)的变化及γ-干扰素(IFN-γ)的干预作用。方法:28只SHR(雄性),随机分为4组(每组7只):高剂量组(SHR-H),中剂量组(SHR-M),低剂量组(SHR-L)和SHR对照组(SHR-C);另7只WKY大鼠(雄性),作为阴性对照组(WKY)。SHR-L组,SHR-M组,SHR-H组每日上午分别腹腔注射INF-γ,5万u/kg,10万u/kg,15万u/kg,连续8w。SHR-C组和WKY组每日上午腹腔注射等量的0.9%氯化钠液,连续8w。分别于治疗前,治疗后4w、8w,采用尾袖法测量尾动脉收缩压(SBP),ELISA法检测血清MMP-9含量。实验第8周,处死大鼠,称取左心室质量(LVM),计算左心室质量指数LVMI(LVWI=LVM/BW);光镜下观察HE染色的心肌组织;采用werstern blot法检测心肌组织MMP-9蛋白表达。结果:各SHR组尾动脉收缩压(SBP)、左心室质量、LVMI及MMP-9的血清水平较WKY组明显升高(P<0.0 5)。应用IFN-γ后,治疗组的各指标较SHR-C均显著下降SBP[(189.57±5.06)vs.(201.57±5.74)mmHg(1 mmHg=0.133kPa)],LVMI[(2.68±0.08)vs.(2.89±0.08)mg/g],MMP-9[(3.20±0.35)vs.(4.90±0.51)mg/L,P<0.05)];心肌组织MMP-9蛋白明显负调表达[(0.49±0.07)vs.(1.05±0.08),P<0.05]。结论:IFN-γ能抑制心肌组织中MMP-9表达,改善高血压心室重构,可能与抑制心肌的慢性炎症有关。

Objective：To investigate the effect of IFN-γ（IFN ppar-gamma）on the expression of Matrix Metalloproteinase-9（MMP-9） and ventriculer remodeling in spontaneously hypertensive rats（SHR）.Methods：28 SHR（male） were randomly divided into 4 groups（each group=7） ： high dose group（SHR-H）,middle dose group（SHR-M）,low dose group（SHR-L） and SHR control group（SHR-C）;The other 7 WKY rats（male） as the negative control group（WKY）.SHR-L group,SHR-M group,SHR-H group were respectively applied of IFN-γ（50 000 units/kg,100 000 units/kg,150 000 units/kg）daily morning intraperitoneal injection for 8w.As well,SHR-C group and WKY group were respectively applied of same amount of saline for eight weeks.Respectively the before treatment and after treatment 4,8w,caudal artery systolic blood pressure（SBP）were measured by the tail sleeve,MMP-9 serum content were detected by ELISA method.By the 8w,putting to death rats,we weighed the left ventricular mass（LVM） and calculated the left ventricular mass index LVMI（LVMI=LVM/BW）.In the myocardial tissue the morphological changes were observed with HE staining and MMP-9 protein expression was analysed by Werstern blot.Results： The SHR group caudal artery systolic blood pressure（SBP）,LVM,LVMI and MMP-9 serum content was significantly higher in all SHR group than WKY group（P0.05）.Application of IFN-γ,SBP [（189.57±5.06）vs.（201.57±5.74）mm Hg（1 mm Hg=0.033 kPa）],LVMI[（2.68±0.08）vs.（2.89±0.08） mg/g],MMP-9[（3.20±0.35）vs.（4.90±0.51）mg/L]（P0.05）,MMP-9 protein in the myocardial tissue were significantly negative control expression[（0.49±0.07）vs.（1.05±0.08）]（P0.05）.Conclusion： IFN-γ can inhibit MMP-9 expression in myocardial tissue,improve hypertension ventricular remodeling,and may be associated with inhibition of myocardial chronic inflammation.