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辛伐他汀预处理对大鼠神经源性肺水肿的作用及其机制 被引量:1

Effect and Potential Mechanisms of Simvastatin Pretreatment on Neurogenic Pulmonary Edema in Rats
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摘要 目的探讨辛伐他汀预处理对大鼠神经源性肺水肿(NPE)的作用及其可能的机制。方法 SD大鼠分为正常对照组、NPE组、辛伐他汀20 mg组、辛伐他汀40 mg组,辛伐他汀组大鼠分别给予20 mg/(kg·d)和40mg/(kg·d)辛伐他汀灌胃4周。干预4周后,除正常对照组大鼠外,其余各组大鼠均采用小脑延髓池穿刺注射复制NPE模型。Kaplan-Meier法比较各组大鼠24 h生存率。造模6 h后采用湿干比重法评估肺水肿程度、HE染色观察肺组织病理变化。并取各组大鼠肺微血管内皮细胞(PMVEC)进行原代培养,流式细胞术观察PMVEC凋亡率,Western blot和RT-PCR分别检测PMVEC的Bax和Bcl-2蛋白及m RNA表达。结果与正常对照组相比,造模后6h,NPE组大鼠肺组织湿干比值显著增加,HE染色可见明显的肺间质及肺泡水肿,生存曲线结果显示大鼠生存率显著下降;NPE组大鼠PMVEC凋亡率显著增加,Bcl-2蛋白和m RNA表达下调,Bax蛋白和m RNA表达上调。与NPE组相比,辛伐他汀20 mg组大鼠肺水肿减轻,生存率改善,PMVEC凋亡率降低,Bcl-2蛋白和m RNA表达上调,而Bax蛋白和m RNA表达下调。与辛伐他汀20 mg组相比,辛伐他汀40 mg组上述变化更显著。结论辛伐他汀预处理可能通过上调PMVEC的Bcl-2、下调Bax m RNA和蛋白表达,抑制PMVEC凋亡,减轻大鼠NPE。提示辛伐他汀可能对NPE有防治作用,但需临床进一步证实。 Aim To explore the effect and potential mechanisms of simvastatin pretreatment on neurogenic pulmonary edema( NPE) in rats. Methods The SD rats were randomly divided into control group,NPE group,simvastatin20 mg group and simvastatin 40 mg group. The rats in the simvastatin group were pretreated with simvastatin for 4 weeks according to 20 mg /( kg·d) and 40 mg /( kg·d) by intragastric administration,respectively. The NPE models of rats except the control group were induced by cerebellomedullary cistern puncture after pretreatment of 4 weeks. The 24 h survival rates of rats were evaluated by Kaplan-Meier method. At 6 h following operation,the severity of pulmonary edema,lung tissue pathological changes of rats were evaluated by Wet Dry proportion method and HE staining,respectively. The apoptosis rate,protein and m RNA expressions of Bcl-2 and Bax of primary cultured PMVEC were detected by flow cytometry,Western blot and RT-PCR,respectively. Results Compared with the control group,the Wet Dry proportion of lung increased significantly,and the pulmonary interstitial edema and alveolar edema of the rats were obvious by HE staining and the apoptosis rate of PMVEC increased significantly at 6 h following operation in the NPE group. The 24 h survival rates of rats in the NPE group decreased significantly. The protein and m RNA expressions of Bcl-2 of PMVEC were downregulated,but the protein and m RNA expressions of Bax were upregulated in the NEP group. While the severity of pulmonary edema and survival rates of the 20 mg /( kg·d) simvastatin pretreatment rats decreased significantly when compared with that of rats in the NPE group. And the apoptosis rate of PMVEC decreased in the 20 mg /( kg·d) simvastatin pretreatment rats. The protein and m RNA expressions of Bcl-2 in the PMVEC were upregulated; but the protein and m RNA expressions of Bax were downregulated in the simvastatin pretreatment rats. When compared with the 20 mg /( kg·d) simvastatin pretreatment rats,these parameters changes more significantly in t
出处 《中国动脉硬化杂志》 CAS 北大核心 2015年第10期995-1000,共6页 Chinese Journal of Arteriosclerosis
基金 湖南省医药卫生科研计划项目(B2013-040) 湖南省科技计划项目(2014SK3088)
关键词 辛伐他汀 神经源性肺水肿 肺微血管内皮细胞 Simvastatin Neurogenic Pulmonary Edema Pulmonary Microvascular Endothelial Cells
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参考文献17

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