低氧性肺动脉高压大鼠肺内fractalkine的变化

The Change of Fractalkine in Lung Tissue of Rat with Hypoxic Pulmonary Hypertension

目的探讨趋化因子fractalkine在低氧性肺动脉高压发病机制中的作用。方法将20只雄性SD大鼠随机分为对照组和低氧组,每组10只,低氧组以常压低氧建立肺动脉高压模型。以右心导管法检测平均肺动脉压(mPAP),图像分析法测量肺小动脉壁厚度,计算出管壁厚度占血管外径的百分比(WT%)和管壁面积占血管总面积的百分比(WA%),逆转录-聚合酶链式反应(RT-PCR)法观察大鼠肺组织fractalkine mRNA的表达和酶联免疫法观察肺组织匀浆fractalkine的变化。结果对照组大鼠mPAP为(16.3±2.1)mmHg(1 mmHg=0.133 kPa),低氧组为(28.7±3.8)mmHg,两组比较差异具有统计学意义(P<0.01);对照组大鼠WT%为(10.20±1.56)%、WA%为(38.11±2.30)%,低氧组大鼠WA%和WT%分别为(21.28±4.60)%和(67.08±9.44)%,两组比较差异均具有统计学意义(P均<0.01);低氧组大鼠肺组织fractalkine mRNA的含量较对照组增加〔(0.49±0.05)vs(0.29±0.02),P<0.01〕,肺组织匀浆fractalkine浓度亦高于对照组〔(7622.6±938.4)pg/mL vs(4168.5±403.5)pg/mL,P<0.01〕。相关分析表明,fractalkine mRNA和蛋白与WA%和WT%均呈正相关(P<0.05)。结论慢性低氧大鼠肺组织fractalkine的合成和释放增多,fractalkine增加可能与低氧性肺动脉高压的发生有关。

Objective To evaluate the role of fractalkine in the pathogenesis of hypoxic pulmonary hypertension. Methods Twenty male SD rats were randomly divided into control group and hypoxic group. Rats in hypoxic group were exposed to hypoxia for 3 weeks. Mean pulmonary arterial pressure （mPAP） was measured by a right cardiac catheterization. The thickness of pulmonary arterioles was measured with a computerized image analyzer. The rates of wall thickness/external diameter （WT%） and wall area/total vascular area （WA%） were calculated. The fractalkine level in lung tissue were measured by enzyme-linked immunosorbent assay. Fractalkine mRNA expression in lung were observed by reverse transcriptase-polymerase chain reaction. Results The rat mPAP of hypoxic group was higher than that of the control group [（28. 7±3.8） mmHg vs （16.3±2. 1） mmHg, P〈0. 01]. The WT% and WA% were increased significantly in hypoxic group than in control group [WT%： （21.28±4. 60）% vs （10. 20±1.56） %, WA% ：（67.08±9.44）% vs （38. 11±2.30） %, P〈0. 01, respectively]. In hypoxic group, the expression of fractalkine mRNA in the lung was significantly up-regulated [（0. 49±0. 05） vs （0. 29±0. 02）, P〈0. 01], the expression level of fraetalkine in lung tissue was higher than that in control group[（7622. 6±938. 4） pg/mL vs （4168. 5±403. 5） pg/mL, P〈0. 01]. Linear correlation analyses showed that fractalkine mRNA and protein were positively associated with WA% and WT%（P〈0. 05）. Conclusion The synthesis and release of fractalkine are increase in the lung tissue of chronic hypoxic rats, and fractalkine may play an important role in hypoxic pulmonary hypertension.