通心络对缺氧预适应小鼠脑组织细胞凋亡因子表达的影响

Effects of Tongxinluo on expression of apoptotic factors in cerebral tissues of hypoxic preconditioned mice

目的:观察缺氧预适应小鼠脑组织细胞凋亡因子表达的变化以及通心络的干预作用。方法:将小鼠随机分为预适应组(对照组)与通心络组2组,通心络组按1.52g生药·kg-1·d-1,灌胃给药,5d后进行实验。2组动物分别进行0次(H0)、1次(H1)、3次(H3)、5次(H5)重复缺氧暴露,小鼠置于低氧密闭罐中,通过小鼠呼吸消耗罐内氧造成罐内低氧,以小鼠出现喘呼吸为低氧耐受极限,然后将小鼠转到另一低氧密闭罐中,依此类推,连续进行5次低氧。观察它们的缺氧耐受时间,以及脑组织缺氧诱导因子1α(HIF-1α)、B细胞白血病/淋巴瘤相关抗原相关X蛋白(Bax)、B细胞白血病/淋巴瘤相关抗原2(Bcl-2)蛋白的表达。结果:随着缺氧次数的增加,对照组与通心络组缺氧耐受时间均依次增强,HIF-1α、Bcl-2蛋白表达逐渐增强(P<0.01或P<0.05);Bax蛋白在1次缺氧时明显增加,后逐渐降低(P<0.01或P<0.05)。与对照组比较,通心络组各次缺氧时间增长,HIF-1α、Bcl-2蛋白表达增强,Bax蛋白表达下降(P<0.01或P<0.05)。结论:缺氧预适应具有强大的自适应能力,HIF-1α、Bcl-2蛋白表达增强和Bax表达下降可能是缺氧预适应小鼠缺氧自适应的机制之一。通心络能够明显增强机体的自适应能力,提高小鼠对急性缺氧的耐受性。

AIM： To observe the effects of Tongxinluo （ TXL） ,a Chinese medicine,on hypoxic tolerance and expression of Bcl-associated X （ Bax） and B-cell leukemia/lymphoma 2 （ Bcl-2） in hypoxia-preconditioned mice. METHODS： The mice were randomly divided into groups of hypoxia preconditioning without （ control group） or with TXL treatment （ TXL group） . The mice in TXL group were administered with TXL at dose of 1. 52 g·kg-1·d-1 crude drug for 5 days. The mouse was exposed to normoxia （ 0 run,H0） and acute repetitive hypoxia for 1-5 runs （ H1-H5） by placing the animal in an air-sealed jar. The hypoxic environment was established in the jar through consumption of the oxygen by the respiration of the mouse. A gasp breath was regarded as the hypoxic tolerant limit of the mouse and the animal was then transferred to another new jar. The mouse was exposed to hypoxia in this way for 5 times. In each run of hypoxic exposure, the time of hypoxic tolerance was measured. Western blotting was used to measure the protein levels of hypoxia inducible factor-1α （ HIF-1α） ,Bax and Bcl-2 in the cerebral cortex. RESULTS： The hypoxic tolerance time in control and TXL groups was gradually increased run by run （ P 0. 01 or P 0. 05） . The protein levels of HIF-1α and Bcl-2 in the two groups were gradually increased （ P 0. 01 or P 0. 05） . Bax in control and TXL groups was significantly increased in H1. After H1,Bax was decreased run by run （ P 0. 01 or P 0. 05） . Compared with control group,the tolerance time,the expression of HIF-1α and Bcl-2 in the cerebral cortex in TXL group were increased in H1,H3 and H5. However,the expression of Bax was lower than that in control group in every run. CONCLUSION： Hypoxia preconditioning makes the organism produce a strong adaptive response. The increase in Bcl-2 and the decrease in Bax may be involved in the mechanism of adaptation. TXL obviously increases the adaptive ability of the mice to hypoxia.