低氧诱导因子-1α和血管内皮生长因子在玉树地震救援人员急性高原反应低氧性肺动脉高压发生中的作用
The role of hypoxia inducible factor-1α and vascular endothelial growth factor in hypoxic pulmonary hypertension in patients with acute high altitude reaction of rescue workers in Yushu earthquake
摘要目的 观察低氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)在急性高原反应(AHAR)低氧性肺动脉高压(HPH)发生中的作用及返回低海拔后的变化。方法 选择2010年4月14日青海玉树大地震后由低海拔(1 500m)快速进入高海拔地区(3 700m)并从事重体力劳动的18~35岁男性官兵96名,根据AHAR症状评分分为无AHAR组(25名)、轻中度AHAR组(47名)和重度AHAR组(24名);在高海拔地区停留50 d后下撤前及返回低海拔地区后12h、15d分别测定平均肺动脉压(mPAP)和血清HIF-1α、VEGF水平。同时选择低海拔地区50名健康官兵作为对照。结果 高海拔无AHAR组mPAP(mm Hg,1 mm Hg=0.133 kPa)和血清HIF-1α(pg/L)、VEGF(ng/L)水平(分别为24.23±1.56、68.80±7.52、82.56±6.32)明显高于低海拔对照组(18.50±1.30、50.95±3.33、65.78±4.03);且随AHAR加重,各指标进一步升高,高海拔轻中度AHAR组分别为28.42±1.32、88.10±9.20、104.82±10.36,重度AHAR组分别为34.70±2.94、117,93±13.46、136.77±12.03,组间两两比较差异均有统计学意义(均P<0.01)。高海拔AHAR总计分与mPAP、血清HIF-1α、VEGF水平均呈显著正相关(r值分别为0.672、0.737、0.634,均P<0.01);mPAP与血清HIF- 1α、VEGF水平呈显著正相关(r值分别为0.706、0.638,均P<0.01)。与低海拔对照组比较,96名官兵进入高海拔地区50 d时mPAP (mm Hg)和血清HIF- 1α (pg/I)、VEGF (ng/L)水平(分别为29.08±4.22、91.16±20.58、107.11±10.32)显著升高(均P<0.01),返回低海拔地区12 h(分别为23.05±3.18、70.99±8.22、78.65±6.47)、15 d(分别为18.96±1.75、52.31±4.92、63.08±4.55)时各指标显著下降,且15d明显低于12 d(均P<0.01),15d时各指标与低海拔对照组比较差异均无统计学意义(均P>0.05)。结论 人体在高海拔低氧地区并从事重体力劳动时,AHAR越重,mPAP和血清HIF-1α、VEGF水平就越高,说明HPH与HIF-1α、VEGF水平升高有密切关系;返回低海拔地区后12h上述指标有显著改善,15d可恢复到正常水平。
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abstractsObjective To assess the effects of hypoxia inducible factor-1a (HIF-1a) and vascular endothelial growth factor (VEGF) on hypoxic pulmonary hypertension(HPH) in patients with acute high altitude reaction(AHAR) and its change after return to lower altitude. Methods Ninety-six officers and soldiers participating in rescue of Yushu megaseism on April 14th in 2010, leaving low altitude area (1 500 m) rapidly to high altitude area(3 700 m) to undertake strenuous physical work were enrolled for study. All of them were male, aged 18 - 35 years, and they were divided into three groups according to the symptomatic scores of AHAR: without AHAR (group B, n= 25), mild to moderate AHAR (group C,n=47) and severe AHAR (group D, n= 24). Mean pulmonary artery pressure (mPAP), levels in serum HIF-lα and VEGF were measured at high altitude area after a stay of 50 days, and also after their return to lower altitude area (1 500 m) for 12 hours and 15 days. Fifty healthy volunteers at low altitude area served as control (group A). Results Level of mPAP (mm Hg, 1 mm Hg=0. 133 kPa), serum HIF-lα (pg/L) and VEGF (ng/L) in group B (24. 23 ± 1.56, 68. 80± 7. 52 and 82.56± 6. 32) were significantly higher than those in group A (18. 50±1.30, 50. 95±3.33 and 65.78∶4. 03), respectively (all P<0. 01). Moreover,the value of all the parameters increased with increase in severity of AHAR, the respective value in group C were 28. 42 ± 1.32, 88. 10 ± 9. 20 and 104. 82 ± 10. 36, and in group D were 34.70 ± 2.94, 117. 93 ± 13.46and 136. 77±12. 03, and there were significant differences in comparing two groups (all P<0. 01). At high altitude area, AHAR total score was positively correlated with mPAP, serum HIF-1α and VEGF (r= 0. 672,0. 737 and 0. 634, respectively, all P<0. 01), mPAP was positively correlated with serum HIF-1α and VEGF (r=0. 706, 0. 638, both P<0. 01). Compared with group A, level of mPAP (29.08±4. 22), serum HIF-1α(91.16±20. 58) and VEGF (107. 11± 10. 32) were significantly increased in 96 officers and soldiers who stayed for 50 days at an altitude of 3 700 m (all P<0. 01), and the values were significantly decreased after returning to lower altitude area for 12 hours (23. 05 ± 3. 18, 70. 99±8.22 and 78. 65±6.47) and 15 days (18. 96± 1.75, 52. 31±4. 92 and 63. 08±4. 55). The values showed significant difference between 12 hours and 15 days stay at 1 500 m (all P<0. 01). The values of the determined parameters 15 days after return to lower altitude area showed no difference compared with those of group A (all P>0. 05). Conclusion Strenuous physical work at high altitude area, AHAR becomes more serious, and it is accompanied by higher values of HIF-1α, VEGF and mPAP, indicating that HPH is closely associated with elevation of HIF-1α and VEGF. These changes are improved after returning to lower altitude area for 12 hours, and they recover to normal lever after 15 days.
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