中文摘要：

目的探讨盐酸法舒地尔（HF）对脂多糖诱导的大鼠血管内皮功能障碍的作用及机制。方法采用随机数字表法将24只雄性Sprague Dawley大鼠分为对照组（不做特殊处理）、HF组（腹腔注射HF 30 mg/kg）、脂多糖组（尾静脉注射脂多糖1 mg/kg）和脂多糖＋HF组（腹腔注射HF 30 mg/kg 0.5 h后，尾静脉注射脂多糖1 mg/kg），每组大鼠均为6只。8 h后处死大鼠，提取主动脉组织。分别采用实时荧光定量PCR、Western blot和免疫组织化学法检测Rho相关的卷曲蛋白激酶1（ROCK1）、缝隙连接蛋白（Cx）43和小窝蛋白（Cav）1的mRNA和蛋白表达水平。结果（1）实时荧光定量PCR显示，脂多糖组ROCK1（2.67±0.03比1.00±0.04）、Cx43（1.73±0.03比1.00±0.08）和Cav1（1.85±0.04比1.0±0.03）的mRNA表达水平均高于对照组（P均〈0.05）；而脂多糖＋HF组ROCK1（0.38±0.02）、Cx43（0.58±0.02）和Cav1（0.27±0.01）的mRNA表达水平均低于脂多糖组（P均〈0.05）。（2）Western blot显示，脂多糖组ROCK1（3.46±0.82比2.19±0.56）、Cx43（0.33±0.09比0.11±0.06）和Cav1（3.45±0.74比2.25±0.91）的蛋白表达水平均高于对照组（P均〈0.05）；而脂多糖＋HF组ROCK1（1.09±0.52）、Cx43（0.01±0.06）和Cav1（2.06±0.40）的蛋白表达水平均低于脂多糖组（P均〈0.05）。（3）免疫组织化学法显示，脂多糖组ROCK1（84.1±0.9比53.7±2.9）、Cx43（99.1±2.1比46.2±0.8）和Cav1（167.0±6.4比84.9±1.0）的蛋白表达水平均高于对照组（P均〈0.05）；而脂多糖＋HF组ROCK1（30.4±0.6）、Cx43（21.4±1.3）和Cav1（55.8±2.8）的蛋白表达水平均低于脂多糖组（P均〈0.05）。结论HF通过降低脂多糖诱导的血管内皮细胞ROCK1、Cx43和Cav－1表达水平增高，改善血管内皮细胞功能障碍。

英文摘要：

ObjectiveTo investigate the effect and mechanism of hydroxyfasudi （HF）, a specific Rho kinase inhibitor, on lipopolysaccharide（LPS）induced endothelial dysfunction. MethodsA total of 24 male Sprague Dawley rats were randomly divided into control group（n=6）, HF group（n=6）, LPS group（n=6） and LPS ＋ HF group（n=6） with random number table method. There was no special treatment in control group. HF （30 mg/kg） was injected intraperitoneally in HF group. LPS （1 mg/kg） were injected intravenously in LPS group. In LPS＋ HF group, HF （30 mg/kg） was injected intraperitoneally, followed by intravenous LPS injection （1 mg/kg） 30 minutes later. All rats were sacrificed after 8 hours, and aortic tissue was extracted. RT-PCR was performed to detect mRNA levels of Rho-associated coiled-coil protein kinase （ROCK）1, connexin （Cx）43 and caveolin （Cav）1. The protein levers of ROCK1, Cx43 and Cav-1 were assessed by Western blot and immunohistochemical staining respectively.Results（1） RT-PCR experiments showed that mRNA levels of ROCK1（2.67±0.03 vs. 1.00±0.04）, Cx43（1.73±0.03 vs. 1.00±0.08）, and Cav1（1.85±0.04 vs. 1.0±0.03） in LPS group were significantly higher than in control group（all P〈0.05）. mRNA levels of ROCK1（0.38±0.02）, Cx43（0.58±0.02）, and Cav1（0.27±0.01） in LPS ＋ HF group were significantly lower than in LPS group（all P〈0.05）. （2）Western blot analysis showed that protein levels of ROCK1（3.46±0.82 vs. 2.19±0.56）, Cx43（0.33±0.09 vs.0.11±0.06）, and Cav1（3.45±0.74 vs. 2.25±0.91） in LPS group were significantly higher than in control group（all P〈0.05）. Protein levels of ROCK1（1.09±0.52）, Cx43（0.01±0.06）, and Cav1（2.06±0.40） in LPS ＋ HF group were significantly lower than in LPS group（all P〈0.05）. （3） Immunohistochemical staining showed that protein levels of ROCK1（84.1±0.9比53.7±2.9）, Cx43（99.1±2.1 vs. 46.2±0.8）, and Cav1（167.0±6.4 vs. 84.9±1.0） in LPS