低氧暴露时间的选择与海拔落差对高原肺动脉高压大鼠模型复制的影响

Effect of selection of suitable time for exposure to hypoxia and altitude difference on high altitude pulmonary hypertension model rats

摘要:

目的 探讨来源于不同海拔大鼠在4 300～5 000 m高原现场或低压氧舱复制高原肺动脉高压大鼠模型时，低氧暴露时间与海拔落差对两种模型复制的影响。方法 采用低压氧舱和高原现场两种模型复制方式。选取西安、成都、兰州、北京不同海拔来源SD大鼠，根据低氧暴露时间不同分别分为第1天组、第3天组、第7天组、第15天组、第21天组和第30天组。模型复制时采用常温和低温，比较低氧暴露时间不同组不同温度下大鼠的肺动脉压；模型复制时海拔不同，比较低氧暴露时间不同组不同海拔大鼠的肺动脉压；采用Peason法分析大鼠来源地海拔和模型复制时海拔的高度落差与肺动脉增幅的相关性。结果 同一海拔低氧暴露不同时间组西安SD大鼠高原现场模型的肺动脉压比较，差异有统计学意义（P <0.05），随着低氧暴露时间的延长，大鼠肺动脉压逐渐升高。低氧暴露不同时间组西安SD大鼠低压氧舱模型同一温度下的肺动脉压比较，差异有统计学意义（P <0.05）。同样6～12℃低温下和常温下，低氧暴露同一时间组西安SD大鼠高原现场和低压氧舱模型的肺动脉压比较，差异均无统计学意义（P >0.05）。低氧暴露第1天组、第7天组、第15天组、第30天组不同海拔来源大鼠4 500 m高原现场模型的肺动脉压比较，差异有统计学意义（P <0.05），来源地海拔较低大鼠的肺动脉压高于来源地海拔较高的大鼠；低氧暴露30 d后，15只西安SD大鼠肺动脉压≥ 30 mmHg，模型复制成功率为100%；17只成都SD大鼠肺动脉压≥30 mmHg，模型复制成功率为100%；10只兰州SD大鼠中只有8只达到要求，模型复制成功率为80%。低氧暴露不同时间组不同海拔来源大鼠5 000 m低压氧舱模型的肺动脉压比较，差异有统计学意义（P <0.05）；低氧暴露21 d后，10只北京SD大鼠肺动脉压≥ 30 mmHg，模型复制成功率为100%；低氧暴露30 d后，10只西安SD大鼠肺动脉压≥ 30 mmHg，模型复制成功率为100%；低氧暴露30 d后，10只兰州SD大鼠中只有8只达到要求，模型复制成功率为80%。大鼠来源地海拔和模型复制时低氧暴露地海拔之间的海拔落差与肺动脉压升高幅度（增幅）呈正相关（r =0.875，P =0.000）。结论 高原现场模型或低压氧舱模型复制的成功率与大鼠的来源地海拔和暴露低氧时间密切相关，在同一海拔进行模型复制时，大鼠来源地海拔越低，其暴露低氧所需时间就越短，反之就越长。而温度并不影响高原肺动脉高压模型的复制。

Abstract:

Objective To investigate the high-altitude pulmonary hypertension animal modeling from different low-altitude rats in the 4,300 to 5,000 m plateau or in the hypobaric hypoxic chamber, and to compare the influence of the altitude difference on the two models.Methods The rats were divided into hypobaric-hypoxic chamber model group and plateau field model group. According to the influence of temperature on model building, they were refined into normal temperature group and low temperature group. According to the influence of the source altitude of the rats, they were further divided into different altitude source groups, and then compare the modeling effects of different modeling methods to evaluate the differences.Results The pulmonary artery pressure of Xi'an SD rats exposed to field hypoxia for different time groups at the same altitude was statistically significant (P < 0.05). With the extension of hypoxia exposure time, the pulmonary artery pressure of rats gradually increased. There was significant difference in pulmonary artery pressure of Xi'an SD rats exposed to simulated hypoxia at different times and at the same temperature (P < 0.05). Similarly, there was no significant difference in pulmonary artery pressure between field and simulated hypoxia exposure groups at 6 to 12℃ and normal temperature (P > 0.05). With Comparing the pulmonary artery pressure of rats from different altitude sources in the field model at 4500m plateau in different time groups of hypoxia exposure, there was significant difference in the first day group, the 7th day group, the 15th day group, and the 30th day group of hypoxia exposure (P < 0.05). The pulmonary artery pressure of rats from low altitude was higher than that of rats from high altitude; After 30 days of hypoxia exposure, the pulmonary artery pressure of 15 Xi'an SD rats was ≥ 30 mmHg, and the success rate of model replication was 100%; The pulmonary artery pressure of 17 Chengdu SD rats was ≥ 30 mmHg, and the success rate of model replication was 100%; Only 8 of the 10 Lanzhou SD rats met the requirements, and the success rate of model replication was 80%. There was significant difference in pulmonary artery pressure between rats exposed to hypoxia for different time groups and 5000 m hypobaric hypoxic chamber model from different altitude sources (P < 0.05); After 21 days of hypoxia exposure, the pulmonary artery pressure of 10 Beijing SD rats was ≥ 30 mmHg, and the success rate of model replication was 100%; After 30 days of hypoxia exposure, the pulmonary artery pressure of 10 Xi'an SD rats was ≥ 30 mmHg, and the success rate of model replication was 100%; After 30 days of hypoxia exposure, only 8 of the 10 Lanzhou SD rats met the requirements, and the success rate of model replication was 80%. There was a positive correlation between the altitude difference between the altitude of the source and the altitude of hypoxia exposure during model replication and the increase of pulmonary artery pressure (r = 0.875, P = 0.000).Conclusion For the plateau field model or the low-pressure oxygen chamber model, the success rate of model replication is closely related to the altitude of the source of rats and the time of exposure to hypoxia. When the model replication is carried out at the same altitude, the rats from the lower altitude need to be exposed to hypoxia for a shorter time. High altitude temperature did not affect the model of pulmonary hypertension.