Protective effect of Rhodiola rosea on vascular endothelium in rats with intermittent hypoxia / 中国中西医结合急救杂志

ABSTRACT

Objective To observe the protective effect of Rhodiola rosea on vascular endothelium in rats with intermittent hypoxia (IH) and to explore its possible mechanism. Methods According to random number table method, 45 male Sprague-Dawley (SD) rats were divided into normal control group, IH group and Rhodiola rosea low, medium and high dose groups, with 9 rats in each group. The IH model was reproduced by putting the rats into IH model chamber, and then feeding them with nitrogen, oxygen and compressed air for 45 days. The feeding bin and feeding time of rats in the normal control group were consistent with those in other groups, and the oxygen concentration in the tank was maintained at 20%-21%. The rats in Rhodiola rosea high, medium and low dose groups were intraperitoneally injected with Rhodiola rosea (0.2, 0.1 and 0.05 mL/100 g), starting from the 15 th day in IH chamber, and the injection continued for 30 days. The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) in the coronary arteries of rats in each group were detected by automatic biochemical analyzer. The contents of coronary hypoxia-inducible factor-1α(HIF-1α) and tumor necrosis factor-α(TNF-α) in rats were determined by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF) in coronary artery tissues of rats in each group were measured by reverse transcription-polymerase chain reaction (RT-PCR). The pathological changes of aorta in each group were observed under light microscope. Results Compared with the normal control group, SOD and NO in the IH group decreased [SOD (U/mg) 4.43±0.22 vs. 8.60±0.34, NO (μmol/g) 3.09±0.07 vs. 4.81±0.41, both P < 0.01], MDA, TNF-α, HIF-1α and mRNA expression of ET-1 and VEGF increased [MDA (nmol/mg) 0.78±0.03 vs. 0.50±0.03, TNF-α(pg/mg) 6.35±0.29 vs. 3.27±0.14, HIF-1α (ng/mg) 14.55±0.70 vs. 7.16±0.17, ET-1 mRNA (2-&Delta;&Delta;Ct) 1.75±0.03 vs. 1.10±0.07, VEGF mRNA (2-&Delta;&Delta;Ct)4.38±0.10 vs. 1.20±0.07, all P < 0.01]. Compared with the IH group, SOD and NO were increased in three Rhodiola rosea groups, MDA, TNF-α, HIF-1α and mRNA expression of ET-1 and VEGF were decreased in three Rhodiola rosea groups, and the changes in the Rhodiola rosea high dose group were more significant than those in the low and medium dose Rhodiola rosea groups [SOD(U/mg) 7.47±0.19 vs. 5.41±0.37, 6.71±0.28, MDA (nmol/mg) 0.57±0.20 vs. 0.74±0.04, 0.70±0.03, NO (μmol/g) 4.00±0.28 vs. 3.27±0.18, 3.47±0.28, TNF-α(pg/mg) 3.90±0.17 vs. 5.08±0.27, 4.39±0.26, HIF-1α(ng/mg) 8.40±0.23 vs. 11.07±0.41, 9.81±0.44, ET-1 mRNA (2-&Delta;&Delta;Ct) 1.12±0.04 vs. 1.71±0.03, 1.63±0.07, VEGF mRNA (2-&Delta;&Delta;Ct) 2.45±0.09 vs. 3.99±0.12, 3.27±0.08, all P < 0.05]. Under light microscope, the inner membrane of the normal control group was intact, and the endothelial cells were loose and slightly stained on the surface of the inner membrane; in the IH group, part of the arterial areas showed endointima edema or even abscission, and interstitial edema in the vascular wall. The pathological changes in three Rhodiola rosea groups were less than that in the IH group, and the changes of Rhodiola rosea high dose group were more significant. Conclusion Rhodiola rosea can protect the vascular endothelium caused by IH exposure through improving the level of anti-hypoxia in tissues and inhibiting oxidative stress and inflammatory response.