激肽原酶对低氧高二氧化碳模型大鼠肺动脉高压的影响  

Effects of Kallikrein on Pulmonary Arterial Hypertension in Rats Induced by Chronic Hypoxic Hypercapnia

作　　者：杨汉文[1] 诸葛毅[2] 王小同[1] 金露[1] 刘银花[1] 袁海[1] 

机构地区：[1]温州医学院附属第二医院康复、脑科中心,325027 [2]衢州学院,浙江324000

出　　处：《医药导报》2010年第8期989-993,共5页Herald of Medicine

基　　金：浙江省自然科学基金资助项目(基金编号:Y2080503)

摘　　要：目的观察激肽原酶对低氧(O2)高二氧化碳(CO2)模型大鼠肺动脉高压的影响。方法将30只雄性SD大鼠随机分为正常对照组(NC组),低O2高CO24周+0.9%氯化钠溶液(HH组),低O2高CO24周+激肽原酶组(HC组),每组10只。HH组与HC组饲养于氧舱中,舱内O2浓度为9%～11%,CO2为5%～6%,q8h,每周6d,共4周,其余时间饲养条件与NC组相同。自第4周开始,进氧舱前:HC组经尾静脉注射激肽原酶,每次剂量为1.6×10-2PNA·kg-1;HH组注射0.9%氯化钠溶液1mL;共6d。第4周末,经颈外静脉插管测量3组肺动脉压;免疫组化、逆转录-聚合酶链反应(RT-PCR)检测肺组织eNOS和eNOSmRNA的表达。结果与NC组比较:HH和HC组的mPAP升高(P<0.01);HH组的右心室与左心室+室间隔质量之比[RV/(LV+S)]升高(P<0.01);HH和HC组的肺小动脉管壁面积/管腔总面积比值(WA/TA)、肺小动脉中膜厚度(PAMT)增高(P<0.01);肺小动脉及支气管eNOS表达降低;肺组织eNOSmRNA表达降低(P<0.01)。与HH组比较:HC组mPAP降低(P<0.01);RV/(LV+S)降低(P<0.01);WA/TA和PAMT降低(P<0.01);肺小动脉及支气管eNOS表达增高;肺组织eNOSmRNA表达增高(P<0.01)。结论激肽原酶上调肺组织eNOSmRNA表达,改善肺血管的重构,降低慢性低O2高CO2模型的大鼠肺动脉高压。Objective To investigate the effects of kallikrein on pulmonary arterial hypertension induced by chronic hypoxic hypercapnia in rats. Methods Thirty male Sprague-Dawley rats were randomly divided into three groups （ 10 in each） ： the control （ NC group ） , hypoxic hypercapnic ＋ normal saline （ HH group ） , hypoxie hypercapnia ＋ Kallikrein group （ HC group）. The rats in both HH and HC groups were placed in the isobaric cabin where concentration of O2 was within 9 % - 11%and concentration of CO2 was maintained within 5 % - 6 % （8 hours/day, 6days/week, total 4 weeks）. At the rest time, they lived under the same condition as those in NC group. At the beginning of the fourth week, the rats in HC group were injected with Urinary Kallidinogenase （1.6×10-2pNA· kg^-1 ） and those in the HH group were injected with normal saline through its tail vein before put into the cabin, for total 6 days. By the end of the 4th week, The mPAP was measured by external jugular vein cannula, the expression of eNOS and eNOSmRNA were detected by immunohistoehemistry and RT-PCR, respectively. Results Compared with the NC group, mPAP, OD of eNOSmRNA, WA/TA（vessel wall area/total area） and PAMT（media thickness of pulmonary arterioles） in both HH and HC groups were significantly higher （P〈0.01）. Compared with the NC group , RV/ （LV＋S） in HH group was significantly higher （P〈0.01）. The expression of eNOS on small arterial and bronchi and eNOSmRNA in pulmonary were lower（ P〈0.01 ）. Compared with the HH group, the values of mPAP, RV/（ LV＋S）, OD of eNOSmRNA, WA/ TA and PAMT in the HC group were significantly lower （ P〈0.01 ）. The expression of eNOS in HC group rats＂ pulmonary was higher. Conclusion Kallikrein may reduce rats＂ pulmonary arterial hypertension induced by chronic hypoxic hypercapnia in our experiment due to activating of eNOS and alleviating vascular remodeling.

关 键 词：激肽原酶 低氧 高碳酸血症 肺动脉高压 ENOS 大鼠 

分 类 号：R972.4[医药卫生—药品]