中文摘要：

目的 探讨孕期炎症刺激对子代大鼠心脏局部肾素血管紧张素系统的影响,为高血压发病机制及其新的防治策略提供实验依据.方法 SD孕鼠12只,采用随机数字表的方法随机分为3组：（1）脂多糖（LPS）模型组（LPS组）：在孕第8、10、12天腹腔注射LPS 0.79 mg/kg;（2）对照组：每只孕鼠腹腔注射无菌生理盐水0.5 ml;（3）LPS＋吡咯烷二硫氨基甲酸（PDTC）组（PDTC组）：在孕第8、10、12天腹腔注射LPS 0.79 mg/kg,孕第8～14天每天腹腔注射核转录因子-κB抑制剂PDTC 100mg/kg.子鼠出生后,免疫组织化学法测定其心脏组织中血管紧张素Ⅱ（AngⅡ）的蛋白表达水平;实时荧光定量PCR测定其心脏组织中血管紧张素转化酶（ACE）、ACE2 mRNA的表达水平;Western blot法检测其心脏组织中ACE、ACE2的蛋白含量.结果 6周和16周时LPS组子代大鼠心肌组织中AngⅡ蛋白表达水平（分别为0.14±0.04和0.17 ±0.04）均明显高于对照组（分别为0.07 ±0.02和0.11 ±0.01）,P分别＜0.01和0.05,PDTC组子代大鼠心肌组织中AngⅡ蛋白表达水平（分别为0.10±0.01和0.13 ±0.03）则明显低于LPS组（P均＜0.05）.6周和16周时LPS组子代大鼠心肌组织中ACE的蛋白表达水平（分别为0.63 ±0.17和0.52±0.11）均明显高于对照组（分别为0.29±0.09和0.34 ±0.07）（P均＜0.05）,16周时ACE mRNA表达水平（1.10±0.26）明显高于对照组（0.72±0.22）（P＜0.05）,PDTC组（0.67±0.01）则明显低于LPS组（P＜0.01）.LPS组ACE2蛋白表达水平（0.47±0.15）明显低于对照组（0.77±0.20）（p＜0.05）,ACE2 mRNA表达水平（0.40±0.02）明显低于对照组（0.90±0.43）（P＜0.05）.结论 孕期炎症刺激引起子代大鼠心脏组织局部ACE和AngⅡ蛋白水平升高,ACE2蛋白水平降低,而其中ACE和ACE2是一对相抗衡、功能效应相反的酶,其表达失衡是子鼠心脏局部肾素血管紧张素系统异常的表现,可能是孕期炎症刺激致子代大

英文摘要：

Objective To explore expression changes of myocardial renin angiotensin system induced by prenatal exposure to lipopolysaccharide in offspring rats.Methods Twelve pregnant SD rats were randomly divided into three groups：LPS model group：intraperitoneal injection of LPS （0.79 mg/kg）at 8,10,12 days of pregnancy ; control group：intraperitoneal injection of sterile saline （0.5 ml） at 8,10,12 days of pregnancy; LPS ＋ PDTC group：intraperitoneal injection of LPS （0.79 mg/kg） at 8,10,12 days of pregnancy plus daily intraperitoneal injection of NF-κB inhibitor-pyrrolidine dithiocarbamate （PDTC,100 mg/kg） on day 8 to 14 pregnancy day.Protein expression of Angiotensin Ⅱ （Ang Ⅱ） in heart was detected by immunohistochemistry; myocardial ACE,ACE2 mRNA expression was detected by real-time PCR; protein expression of ACE and ACE2 in heart was detected by Western blot in offspring rats of various groups.Results Compared with control group （0.07 ± 0.02,0.11 ± 0.01）,Ang Ⅱ protein levels （0.14 ± 0.04） were significantly increased at 6 weeks （P ＜ 0.01） and 16 weeks （0.17 ± 0.04,P ＜ 0.05） in offspring rats of LPS model group,which could be significantly attenuated by PDTC intervention （0.10 ± 0.01,0.13 ± 0.03,respectively,all P ＜ 0.05）.Similarly,myocardial ACE mRNA expression in 16 weeks offspring rats of LPS model group was significantly upregulated compared with control group （1.10 ± 0.26 vs.0.72 ± 0.22,P ＜ 0.05）,which was significantly attenuated by PDTC intervention （0.67 ± 0.01,P ＜ 0.01 vs.LPS group）.Myocardial protein expression ACE2 in 16 weeks offspring rats of LPS model group was significantly downregulated compared to control group,which was slightly upregulated by PDTC intervention （P ＞ 0.05）.Conclusion Pregnancy exposure to lipopolysaccharide increases myocardial ACE and Ang Ⅱexpression while reduces myocardial ACE2 expression in offspring rats,which might be one of the pathomechanisms of offspring hypertension.