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- 2018
盐酸法舒地尔对脂多糖诱导的大鼠血管内皮功能障碍的影响
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Abstract:
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的影响。方法 清洁级雄性SD大鼠80只，采用随机数字表法分为正常对照组、模型组、实验A组和实验B组，每组20只。实验A组、实验B组和模型组尾静脉注射脂多糖(1mg/kg)建立大鼠内皮功能障碍模型。0.5h后，实验A组和实验B组分别腹腔注射10mg/kg和30mg/kg HF，模型组和对照组分别注射等量9g/L生理盐水，连续4周，每天按上述方法注射1次。取各组大鼠胸主动脉标本，TUNEL法检测细胞凋亡，RT-PCR和Western blot分别检测Cx43、Cav-1、eNOS、RhoA和ROCK1的mRNA和蛋白表达。结果 模型组、实验A组和实验B组内皮细胞凋亡指数显著高于对照组(P<0.05)；实验A组和实验B组内皮细胞凋亡指数显著低于模型组(P<0.05)，且实验B组内皮细胞凋亡指数显著低于实验A组(P<0.05)。 模型组Cx43、Cav-1、RhoA和ROCK1的 mRNA和蛋白表达水平显著高于对照组(P<0.05)，eNOS mRNA和蛋白表达水平显著低于对照组(P<0.05)；实验A组和实验B组Cx43、Cav-1、RhoA、ROCK1和eNOS mRNA和eNOS蛋白表达水平显著低于对照组(P<0.05)；实验A组和实验B组Cx43、Cav-1、RhoA和ROCK1 mRNA和蛋白表达水平显著低于模型组(P<0.05)，eNOS mRNA和蛋白表达水平显著高于模型组(P<0.05)；实验B组Cx43、Cav-1、RhoA和ROCK1 mRNA和蛋白表达水平显著低于实验A组(P<0.05)，而eNOS mRNA和蛋白表达水平显著高于实验A组(P<0.05)。结论 HF可能通过RhoA/Rho激酶信号转导通路，抑制RhoA和ROCK1的表达，从而抑制Cx43、Cav-1，而且可提高eNOS表达水平，从而改善血管内皮功能障碍。
ABSTRACT: Objective To investigate the effect of fasudil hydrochloride (HF) on lipopolysaccharide-induced vascular endothelial dysfunction in rats. Methods Eighty SD rats of clean grade were randomly divided into normal control group, model group, experiment group A and group B, with 20 in each. Experiment group A and group B and model group were injected with lipopolysaccharide (1mg/kg) to establish rat model of endothelial dysfunction. After 0.5 hours, 10mg/kg and 30mg/kg HF were injected intraperitoneally into experiment group A and group B, respectively. Rats in model group and control group were injected with 0.9% saline for 4 consecutive weeks according to the above injection method once a day. The expressions of Cx43, Cav-1, eNOS, RhoA and ROCK1 mRNA and protein were detected by RT-PCR and Western blot, respectively. Apoptosis was detected by TUNEL method. Results The apoptosis index of endothelial cells in group A and group B and model group was significantly higher than that in control group (P<0.05). It was significantly lower in experiment group A and group B than in model group (P<0.05). It was significantly lower in experiment group B than in group A (P<0.05). The mRNA and protein expressions of Cx43, Cav-1, RhoA and ROCK1 in model group were significantly higher than those in control group (P<0.05), and the mRNA and protein expressions of eNOS were significantly lower than those in control group (P<0.05). The mRNA and protein expressions of Cx43, Cav-1, RhoA, ROCK1 and eNOS in experiment group A and group B were significantly lower than those in control group (P<0.05). The mRNA and protein expressions of Cx43, Cav-1, RhoA and ROCK1 were significantly higher in experiment group A and
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