慢性间歇低氧对大鼠炎症反应和血管内皮损伤的影响

Effect of chronic intermittent hypoxia on inflammation and vascular endothelial injury in rats

目的建立慢性间歇低氧大鼠模型,探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)与炎症反应、血管内皮损伤的关系。方法 20只大鼠随机分为常氧组和慢性间歇低氧(chronic intermittent hypoxia,CIH)组,CIH组大鼠置于间歇低氧舱8 h/d。8周后处死大鼠,ELISA检测血清白细胞介素-10(IL-10)、人软骨糖蛋白39(YKL-40)含量;HE染色观察主动脉血管内皮;免疫组化检测主动脉核因子κB(NF-κB)、YKL-40表达。结果 (1)CIH组大鼠PO2、SaO2随舱内氧浓度变化改变;常氧组PO2、SaO2基本保持不变。(2)血清指标:CIH组IL-10浓度低于常氧组(P<0.05),两组YKL-40浓度无统计学差异;HE染色:CIH组大鼠主动脉血管内皮损伤;免疫组化:CIH组NF-κB表达高于常氧组(P<0.05);两组大鼠血管几乎无YKL-40表达。结论CIH导致主动脉血管内皮损伤,其机制与炎症相关因子表达失衡有关。

OBJECTIVE A chronic intermittent hypoxia model in rat was established to detect the expression of IL-10, YKL-40 in serum and NF-kB, YKL-40 in aortic endothelial system. To explore the relationship among obstructive sleep apnea hypopnea syndrome(OSAHS), inflammatory response and vascular endothelial injury. METHODS 20 Wistar rats were randomly assigned to 2 groups: chronic intermittent hypoxia and normoxia control groups. The rats in CIH groups were exposed to experimental cabin with 8 hours daily intermittent hypoxia stimulation, while those in normoxia control groups were exposed to normoxia cabin. After 8 weeks, IL-10, YKL-40 concentrations in serum were measured by ELISA. The feature of the general pathological changes were observed by HE staining and the expressions of NF-kB, YKL-40 protein in Endothelium of aorta were observed by immunohistochemistry staining. RESULTS The PO2 and SaCh in CIH group were felled first and then increased, which were similar with the change of oxygen concentration in the chamber. ELISA assay of serum: serum level of IL-10 was significantly decreased in CIH group(P<0.05). There were no specific difYerences of the concentration of YKL-40 in serum between CIH group and normoxia control group(P>0.05);HE staining of aorta: In normoxia control group, the aortic vascular endothelium was smooth without exfoliation. In CIH group, the aortic vascular endothelium was not smooth, and endothelial cells were locally absent. Immunohistochemistry staining of aorta: The expression of NF-kB in aorta in CIH group was obviously increased compared with which in the normoxia control group(P<0.05). There were no specific differences of the expression of YKL-40 in aorta between CIH group and normoxia control group. CONCLUSION Chronic intermittent hypoxia induced vascular endothelial injury,whose mechanism was likely to do with the decrease of serum level of IL-10 and the increasing expression of NF-kB in aorta.