葛根素联用氯沙坦对肾性高血压大鼠心肌MMP-1/TIMP-1比值的影响

Effect of puerarin combined with losartan on ratio of MMP-1 /TIMP-1 in myocardium in renovascular hypertensive rats

目的观察葛根素联用氯沙坦对肾性高血压大鼠心肌MMP-1/TIMP-1 mRNA及蛋白表达比值的影响。方法 SD大鼠65只,雄性,随机抽取8只为假手术组,其余采用两肾一夹法造成肾性高血压大鼠模型。造模成功的大鼠随机分成葛根素高、中、低剂量组,氯沙坦组,联用组以及模型组(n=8)。连续给药8周后计算左心室质量指数(LVWI),Masson染色观察胶原纤维改变,并计算心肌胶原容积分数;测心肌羟脯氨酸(HYP)、血管紧张素Ⅱ(AngⅡ)水平,RT-PCR及Western blot测心肌基质金属蛋白酶-1(MMP-1)及基质金属蛋白酶抑制剂-1(TIMP-1)mRNA及蛋白表达。结果与模型组相比,各用药组心肌胶原容积分数、HYP水平降低(P<0.01或P<0.05),联用组效果最好(P<0.05);葛根素高、中剂量组和联用组心肌AngⅡ水平显著降低(P<0.01或P<0.05),联用组效果最好(P<0.05);除葛根素低剂量组外其他用药LVWI显著降低(P<0.01或P<0.05),MMP-1与TIMP-1 mRNA及蛋白表达的比值显著降低(P<0.05),联用组效果最好(P<0.05)。结论葛根素联用氯沙坦能显著下调心肌局部MMP-1/TIMP-1 mRNA及蛋白比值,改善肾性高血压大鼠心肌纤维化。

AIM To study the effect of puerarin combined with losartan on the ratio of MMP-1/TIMP-1 mRNA and protein expression in myocardium in renovascular hypertensive rats. METHODS Sixty-five male SD rats were used. Eight rats were randomly selected as sham operation group, and the rest were used to make two-kidney-one- clip Goldblatt model. The rats that met the criterion for Goldblatt hypertensive rat were randomly assigned into six groups, high-, middle- and low-dose puerarin groups, losartan group, combination group and model group. After being administered for eight weeks, LVWI （left ventricular weight index） was measured. Myocardial collagen fi- bers were evaluated through Masson trichromestaining; CVF （collagen volume fraction） of myocardium was also measured. The contents of HYP （hydroxyproline） and Ang Ⅱ （ angiopoietin- Ⅱ ） in myocardium were measured. The InRNA and protein expression of MMP-1 and TIMP-1 in myocardium were measured by RT-PCR and Western blot. RESULTS Compared with the model group, CVF and the content of HYP in myocardium in all drug-treated groups significantly decreased （P 〈 0.01 or P 〈 0.05 ） , and the above-mentioned effects were the best in the com- bination group （P 〈 0. 05）. The contents of Ang Ⅱ in myocardium in puerarin high-, middle-dose groups and the combination group markedly decreased （ P 〈 0. 01 or P 〈 0. 05 ）, and those in the combination group were the low- est. LVWI significantly decreased （P 〈 0. 01 or P 〈 0.05 ） in all drug-treated groups except low-dose puerarin.The ratio of MMP-1/TIMP-1 mRNA and protein expression markedly decreased （ P 〈 0. 05 ）, and those of the com- bination group （P 〈 0. 05 ） decreased the most. CONCLUSION A combination of puerarin with losartan can down-regulate the ratio of MMP-1/TIMP-1 mRNA and protein expression in myocardium, and improve myocardial fibrosis in renovascular hypertensive rats.