胰激肽原酶对自发性高血压大鼠心肌转化生长因子-β_1表达及胶原重构的影响

Effects of pancreatic kininogenase on expression of TGF-β_1 and collagen remodeling in spontaneously hypertensive rats

目的:观察胰激肽原酶对自发性高血压大鼠(SHR)左室肌转化生长因子-β1(TGF-β1)表达及胶原网络重构的影响并探讨其机制。方法:雄性15周龄SHR24只,随机分成SHR组、胰激肽原酶组及卡托普利组,每组8只,另取8只雄性同龄健康Wistar大鼠作为正常血压对照组。胰激肽原酶腹腔注射(7.2U.kg-1.d-1),卡托普利组灌胃给药(10mg.kg-1.d-1),SHR组和正常血压对照组给予0.9%NaCl溶液腹腔注射(2mL.kg-1.d-1)。实验4周后行颈动脉插管测量血压,然后处死动物,测量各组左心室重量指数(LVMI)、心肌胶原体积比例(CVF)、心肌血管周围胶原与管腔面积的比例(PVCA)及左室肌TGF-β1的表达。结果:SHR组收缩压(SBP)、LVMI、CVF、PVCA增高(P<0.05),TGF-β1的表达量增加,与正常血压对照组比较,差异均具有显著性(P<0.05)。用药4周后,胰激肽原酶组SBP、LVMI、CVF、PVCA及TGF-β1均较SHR组显著下降,两组比较差异均具有显著性(P<0.05);胰激肽原酶组SBP高于卡托普利组(P>0.05),其他各项指标与卡托普利组比较差异无显著性(P>0.05)。结论:胰激肽原酶具有减轻SHR心肌胶原网络破坏及反应性胶原过度沉积的作用,其机制可能与抑制心室肌高表达的TGF-β1有关。

Objective To detect the effects of pancreatic kininogenase on the expression of TGF-β1 and collagen remodeling in myocardiom of spontaneously hypertensive rats （SHR）. Methods Twenty-four male SHR （aged fifteen weeks） were randomly divided into three groups： SHR group, pancreatic kininogenase group and captopril group （n=8）,8 male Wistar Kyoto rats with normol blood pressure was considered as control group. Pancreatic kininogenase was given by peritoneal injection （7.2 U · kg^-1 · d^-1）, captopril was given by intragastric administration （10 mg · kg^-1 · d^-1）, the rats in SHR group and control group were administered with 0.9% NaCl （2 mL · kg^-1 · d^-1） through peritoneal injection. After four-week experiment, the pressure was measured in rats througth carotid artery , the rats were sacrificed and left ventricular mass index, collagen volume fraction, peripheral vascular collagen area were measured. Myocardial tissue was stained with VG and pathological changes were observed. The expression of TGF-β1 were detected by immunohistochemical technique （SP method）. Results The systolic blood pressure, left ventricular mass index, collagen volume fraction, peripheral vascular collagen area and the expression level of TGF-β1 in SHR group were obviously higher than those in control group （P〈0.05）. After treatment with pancreatic kininogenase for 4 weeks, all the indexes in pancreatic kininogenase group were obviously reduced compared with SHR group （P〈0.05）; but except systolic blood pressure, there were no significant differences of various indexes between pancreatic kininogenase and captopril groups （P〈0.05）. Conclusion Pancreatic kininogenase can obviously control pressure and reverse myocardial fibrosis probably by decreasing the expression of TGF-β1 in SHR.