胰激肽原酶对自发性高血压大鼠氧化损伤和心肌纤维化的影响

Effects of pancreatic kininogenase on lipid peroxidation and myocardial fibrosis in spontaneously hypertensive rats

目的探讨胰激肽原酶对自发性高血压大鼠(SHR)抗氧化损伤和心肌纤维化的影响。方法15周龄雄性SHR大鼠24只,随机分成SHR对照组、胰激肽原酶小剂量组、大剂量组,每组8只。另取8只WKY大鼠作为正常血压对照组。小剂量组(7.2 U.kg-1.d-1)和大剂量组(14.4 U.kg-1.d-1)给予胰激肽原酶腹腔注射。治疗4 w后,测量各组收缩压(SBP)、左心室重量指数(LVM I)、心肌胶原容积分数(CVF)和心肌血管周围胶原面积(PVCA),同时测定血清中超氧化物岐化酶(SOD)、丙二醛(MDA)含量。结果治疗组SBP、CVF、PVCA与SHR对照组比较明显降低(P<0.05),仍未达到WKY组水平(P<0.05)。治疗组血清中SOD含量明显上升,MDA含量下降,与WKY组差异无显著性。结论胰激肽原酶能降低血压,减轻过氧化损伤,逆转心肌纤维化。且无明显毒副作用,有望成为治疗高血压左室肥厚新的有效药物。

Objective To investigate the effects of pancreatic kininogenase on lipid peroxidation and myocardial fibrosis in spontaneously hypertensive rats （SHRs）. Methods 24 fifteen-week male SHRs were randomly and averagely divided into SHR control group, lowdose and high-dose group. Another 8 male WKY rats with normal blood pressure were served as control group. Low-dose group （7.2 u·kg^-1·d^-1） and high-dose group（ 14.4u·kg^-1·d^-1） were treated with intraperitoneal injection of pancreatic kininogenase. The systolic blood pressure（ SBP）, left ventricular mass index（ LVMI）, collagen volume fraction （CVF） and perivascular circumferential area （PVCA） of each group were measured as well as the concentration of serum super oxide dismutase （SOD） and methane dicarboxylic aldehyde （MDA） 4 weeks after treatment. Results SBP, CVF and PVCA of treated groups were significantly decreased compared with those of SHR control group（P 〈0.05） ,but had not reached the level of WKY group. The concentration of serum SOD increased, while MDA decreased in treated group, having no difference with those in WKY group. Conclusions Pancreatic kininogenase can reduce blood pressure, inhibit lipid peroxidation and reverse myocardial fibrosis without significant side effect, which may become a new and effective drug of treating left ventricular hypertrophy.