5-羟基癸酸盐对大鼠低氧性肺动脉高压的抑制作用  

Inhibitory effect of 5-hydroxydecanoate on pulmonary arterial hypertension induced by hypoxia in rats

作　　者：张丽萍[1] 李秋[1] 舒鹰[1] 李云雷[1] 陈成水[1] 

机构地区：[1]温州医学院附属第一医院呼吸内科,浙江温州325000

出　　处：《中国药理学与毒理学杂志》2011年第4期358-363,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：浙江省自然科学基金项目(Z2080988)~~

摘　　要：目的探讨5-羟基癸酸盐(5-HD)对肺动脉高压形成的影响机制及炎症因子的作用。方法 SD大鼠在常压9.5%～10.5%O2的低氧舱中进行低氧处理,每天8 h,每周6 d。1周后,按照分组每天先sc给予5-HD 5 mg.kg-1,再进低氧舱,连续3周。右心导管法测平均肺动脉压(mPAP),测定心脏右心肥厚指数(RVHI),光镜下观察肺血管形态学改变,并用图像分析法测定肺动脉相对中膜厚度(PAMT)。ELISA法检测血清及肺匀浆中白细胞介素6(IL-6),IL-8,巨噬细胞炎症蛋白(MIP)-1a和单核细胞趋化蛋白(MCP)-1含量,免疫组化法测定肺组织中IL-6及MCP-1的表达。结果与正常对照组相比,低氧模型组大鼠mPAP,RVHI及PAMT明显增加(P<0.05);与低氧模型组相比,给予5-HD组明显降低(P<0.05)。与正常对照组相比,低氧模型组大鼠血清IL-6,IL-8,MIP-1a及MCP-1水平增高(P<0.05);与低氧模型组相比,给予5-HD组大鼠血清IL-8,MIP-1a及MCP-1水平明显降低(P<0.05)。结论 5-HD可能是通过抑制肺动脉高压大鼠血清中的某些炎症细胞因子的表达、下调大鼠炎症细胞因子分泌,达到降低肺动脉高压的作用。OBJECTIVE To expolre the effect of 5-hydroxydecanoate（5-HD） on pulmonary arterial hypertension（PAH） induced by hypoxia and the mechanism.METHODS SD rats were kept in the tank with normal atmospheric pressure and 9.5%-10.5% O2,8 h per day,6 d for a week.One week later,before entering the tank,PBS or 5-HD 5 mg·kg-1 was sc given first for 3 weeks before the rats entered the tank.Mean pulmonary arterial pressure（mPAP） was measured by right cardiac catheterization.Right ventricular hypertrophy index（RVHI） and relative pulmonary artery medial thickness（PAMT） were measured.The pulmonary vascular remodeling was observed by a light microscopy.Serum and lung homogenate interleukin 6（IL-6）,IL-8,macrophage inflammatory protein（MIP）-1a and monocyte chemoattractant protein（MCP）-1 level were measured by enzyme-linked immunosorbent assay.The expression of IL-6 and MCP-1 in the pulmonary artery and bronchia was analyzed by immunohistochemistry.RESULTS Compared with normal control group,mPAP,RVHI and PAMT in the PAH model group were significantly increased（P0.05）.Compared with the PAH model group,they were significantly decreased in PAH＋5-HD group（P0.05）.The expression levels of IL-6,IL-8,MIP-1a and MCP-1 in the serum of the PAH model group were much higher than in the normal control group（P0.05）.Compared with the PAH model group,the expression levels of IL-8,MIP-1a and MCP-1 were significantly attenuated in PAH＋5-HD group（P0.05）.CONCLUSION 5-HD can inhibit some inflammatory factors in the serum of PAH model rats and lower the secretion of inflammatory cytokines to reduce PAH induced by hypoxia.

关 键 词：5-羟基癸酸盐 高血压 肺性 白细胞介素6 巨噬细胞炎症蛋白质1 

分 类 号：R96[医药卫生—药理学]