低氧对大鼠右心室肥厚及心肌中缝隙连接蛋白43表达的影响

Effect of Hypoxia on the Right Ventricular Hypertrophy and Expression of Connexin 43 in Rats

目的:研究低氧对大鼠右心室肥厚及心肌中缝隙连接蛋白43(Cx43)表达的影响。方法:40只健康雄性SD大鼠随机分为正常组(control)、低氧3周组、低氧4周组和低氧5周组。除正常组外,其余3组大鼠分别在低氧环境中饲养3周、4周和5周。测定和比较各组大鼠的平均肺动脉压力(mPAP)、右心室收缩压(RVSP)、右心室肥厚度[RV/(LV+S)%],并通过免疫组化染色法观察各组大鼠左心室心肌细胞中cx43的表达。结果:与正常组相比,低氧3周、4周、5周组大鼠的mPAP、RVSP、右心室肥厚度均显著升高(P均<0.05),与低氧3周组比较,低氧4周、5周组大鼠的mPAP、RVSP、右心室肥厚度均显著升高(P均<0.05),而低氧5周组大鼠的mPAP、RVSP、右心室肥厚度均显著高于低氧4周(P均<0.05)。免疫组织化学结果显示:低氧组大鼠Cx43排列紊乱,端-端连接减少,侧面连接增多;随着低氧时间的延长,大鼠心肌细胞中Cx43的表达逐渐减少,差异具有统计学意义(P均<0.05)。结论:低氧可导致右心室肥厚,并随着诱导时间的延长而逐渐加重,这可能与心肌中Cx43的分布紊乱及表达减少有关。

Objective： To investigate the effect of hypoxia on the right ventricular hypertrophy and expression of connexin 43 in rats. Methods： Forty male Sprague-Dawley rats were randomly divided into 4 groups： normoxia control（control）, 3 weeks hypoxia（3w）, 4 weeks hypoxia （4w） and 5 weeks hypoxia （5w）. The rats in normoxia control stayed in normal environment. The rats in 3w hypoxia, 4w hypoxia and 5w hypoxia had been kept respectively in hypoxia chamber for 3 weeks, 4 weeks and 5 weeks to establish the HPH animal model. After HPH rats were established, the mean pulmonary pressure （mPAP） and the right ventricular systolic pressure （RVSP） were recorded. RV/（LV＋S） ratio was calculated to assess right ventricular hypertrophy, expression and location of connexin43 was detected by immunohistochemistry. Results： Compared with normoxia control, the mPAP, RVSP and RV/ （LV＋S）% of 3w, 4w and 5w hypoxia rats increased significantly （P〈0.05）; compared with 3w hypoxia rats, the mPAP, RVSP and RV/ （LV＋S）% of 4w and 5w hypoxia rats increased significantly（P〈0.05）; the mPAP, RVSP and RV/（LV＋S）% of 5w hypoxia rats were all significantly higher than those in 4w hypoxia rats （P〈0.05）. Immunohistochemistry results showed that Cx43 label largely confined to the intercalated disks of the right ventri- cles myoctes in normal rats; exposed to hypoxia, right ventricles myocytes from hypoxia rats showed Cx43 dispersion of punctuate Cx43 labeling over the entire surface, the proportion of Cx43 labeling at the intercalated disk decreased significantly （P 〈0.05）. Conclusion： Hypoxia induced right ventricular hypertrophy in rats, the derangements and low-expression of Cx43 may be involved.