摘要
目的 通过模拟阻塞性睡眠呼吸暂停低通气综合征患者睡眠过程中反复发生的间歇低氧/再氧合过程,建立慢性间歇低氧模型,测定大鼠血清中氧化应激及炎症反应指标、甲状腺激素、大鼠甲状腺中peroxiredoxins5的表达及观察间歇缺氧对大鼠甲状腺超微结构的影响,探讨导致这种关联的可能机制。方法 将16只雄性SD大鼠随机分为间歇低氧组和对照组,间歇低氧组8只大鼠放入间歇低氧模拟舱内,向舱内循环充入氮气、氧气和压缩空气,循环周期为120s,舱内最低氧浓度6%-7%。将对照组大鼠于每天相同时间置于相同规格的动物饲养舱内,并通入相同流量的空气,实验时间设计为每天8h,持续4周,共28d。第29天处死大鼠后,测定大鼠血清丙二醛 （MDA）、超氧化物歧化酶 （SOD）、谷胱甘肽过氧化物酶 （GSH-Px）、白介素6 （IL-6）、肿瘤坏死因子α （TNF-α）、游离三碘甲状腺原氨酸 （FT3）、游离甲状腺素 （FT4）、促甲状腺素 （TSH）,于电镜下观察大鼠甲状腺超微结构的改变,用免疫组化方法测定大鼠甲状腺中Peroxiredoxin5表达。结果 ①间歇低氧组大鼠血清 MDA、IL-6、TNF-α水平较对照组升高,差异有统计学意义 （P〈0.05）;间歇低氧组大鼠血清SOD、GSH-Px较对照组降低差异有统计学意义 （P〈0.05）。②间歇低氧组大鼠血清FT3水平较对照组升高,差异无统计学意义 （P〉0.05）;间歇低氧组大鼠血清FT4、TSH水平较对照组降低,差异有统计学意义 （P〈0.05）。③间歇低氧组大鼠甲状腺超微结构：整体表现为缺氧改变。④甲状腺peroxiredoxins5的阳性染色主要位于甲状腺细胞的胞浆中,大鼠甲状腺Peroxiredoxin5表达：与对照组比较,间歇低氧组大鼠甲状腺Peroxiredoxin5表达升高且差异有统计学意义 （P〈0.05）。结论 间歇低氧大鼠体内存在明显的氧化应激状态及炎症反应,间歇低氧对大鼠甲状腺具有明显刺激作用,会直接损害甲状腺的结构及功能,加重甲状腺氧化应激水平,进而引起甲状腺激素分泌紊乱、靶器官损伤。
Objective To mimic the intermittent hypoxia during sleep of obstructive sleep apnea hypopnea syndrome （OSAHS） in humarL. We established imtermittenthypoxia （IH） animal model in rats, to investigate the oxidative stress, inflammation reaction, thyroid hormone levels, thyroid ultrastructure and the expression of thyroid Peroxiredoxin5 in rats of intermittent hypoxia. Methods Healthy Sprague Dawley （SD） rats （16） were randomly divided into 2 groups：the control group and the IH group. The rats in IH group were placed in an animal chamber subjected to imtermittent hypoxia. Circulation to the cabin filled with nitrogen, oxygen and compressed aircycle of 120 s, the minimum oxygen concentration in cabin was to 6%-7%. Experimental design for about 8 hours every day, 7 days a week, for 4 weeks, a total of 28 days. The rats in control group were placed in the same animal chamber at the same time every day andaccessed to the same flow of air. After the experiment, we measured the level of superoxide dismutase （SOD）, glutathione peroxidase （GSH-Px）, interleukin 6 （ IL-6 ）, tumor necrosis factor-a （ TNF-a）, free triiodothyroxine （FT3）, free thyroxine （FT4）, thyroid, stimuation hormonle （TSH） in rats serum, and observed the changes of rat thyroid ultrastructure under electron microscope, and measured Peroxiredoxin5 expression in rat thyroid by immunohistochemistry. Results ① The levels of MDA and IL-6 and TNFa in rats serum was increased in IH group, and had a significant difference （ P〈0.05）. The levels of SOD and GSH Px in rats serum was discreased in IH group, and showed significant difference （ P〈0.05）. ②The levels of FT8 in rats serum was increased in IH group, hut did not show significant difference （ P〈0.05）. The levels of FT4 and TSH in rats serum was increased in 1H group, and showed significant difference （ P〈0.05）. ③ Ultrastructure of rat thyroid in IH group： Change of hypoxia overall. ④Peroxiredoxin5 positive staining cells mainly located in the cytoplasm of the thyroid. Compared with the control group, Peroxiredoxin expression in rat thyroid was higher in IH group, and had a significant difference （ P〈0.05）.Cenclusiens There are obviously inflammation reactions in rats of intermittent hypoxic. Intermittent hypoxia on the thyroid has a significant stimulating effect, which can directly damage the structure and function of the thyroid, also can increase the level of oxidative stress thyroid, eventually cause thyroid hormone secretion disorders, target organ damage.
作者
徐鹏
余勤
Xu Peng;Yu Qin(Department of Respiratory Medicine, the Affiliated Hospital of Mongolia Medical University, Hohhot 010010, China)
出处
《国际呼吸杂志》
2018年第10期751-757,共7页
International Journal of Respiration
