用阻塞性睡眠呼吸暂停低通气综合征动物模型研究vaspin与胰岛素信号通路的相关性

 目的:通过建立阻塞性睡眠呼吸暂停低通气综合征（OSAHS）大鼠模型，检测其vaspin的血清学以及mRNA、蛋白水平的表达特点，阐述脂肪因子vaspin在OSAHS发生过程中的作用机制。方法: 用慢性间歇低氧（CIH）模拟OSAHS。健康雄性Wistar大鼠22只，随即分为空白对照(control)组和CIH组。每天将CIH组大鼠放入间歇性低氧舱内,共8周。实验前后应用大鼠尾压测量仪测量血压。实验结束后处死动物，检测空腹血糖（FPG）、总胆固醇（TC）、甘油三酯(TG)、空腹胰岛素(FINS)、vaspin和脂联素。应用实时荧光定量PCR和蛋白印迹法（Western blotting）检测vaspin mRNA以及vaspin、Akt、p-Akt蛋白水平。结果: （1）慢性间歇性缺氧下血气结果：缺氧最低点时大鼠动脉血氧分压23.4 mmHg~32.8 mmHg，最低血氧饱和度范围为40.8%~65.9%，恢复舱内氧浓度至21%后，测得动脉血氧分压为74.5 mmHg～102.9 mmHg，动脉血氧饱和度为93.8%~98.9%。（2）实验前后2组大鼠之间比较体重均无显著差异；血压变化实验前2组大鼠尾动脉收缩压无显著差异，实验后2组大鼠之间比较，CIH组大鼠收缩压明显高于正常对照组。CIH组和control组比较，FPG、FINS、TG和TC均升高，差别有统计学意义（P<0.05）。（3）Pearson相关分析显示，血清vaspin水平与FPG、FINS、HOMA-IR和TC呈正相关。（4）CIH组大鼠脂肪组织的vaspin mRNA和蛋白质的表达水平均增加，差别有统计学意义（P<0.01）；Akt mRNA 表达水平无明显改变,但CIH组的p-Akt蛋白水平较control组降低。结论: OSAHS动物模型中vaspin|水平的改变可能在胰岛素抵抗发生过程中具有一定作用。

Vaspin and insulin signaling pathways in obstructive sleep apnea-hypopnea syndrome animal model

AIM: To establish a suitable chronic intermittent hypoxia (CIH) model in rats for modeling the obstructive sleep apnea-hypopnea syndrome (OSAHS) and further to explore the relationship between vaspin and insulin signaling pathways at mRNA and protein levels. METHODS: Healthy male Wistar rats were divided into control group and CIH group. The rats in control group were raised under physiological condition, and the rats in CIH group were kept in the plexiglass chamber between 9:00~17:00 and underwent intermittent hypoxic challenge 8 h/d for 8 weeks. The blood pressure of arteria caudilis in the rats was measured by tail cannulation before and after study. Fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), fasting insulin (FINS), vaspin and adiponectin levels were measured. The mRNA expression of vaspin was detected by real-time PCR. The protein levels of vaspin, Akt and p-Akt were determined by Western blotting.RESULTS: Before the experiment, the weight and blood pressure of the rats had no significant difference, while after the experiment the blood pressure in CIH group was obviously higher than that in control group. FPG, FINS, TG and TC in CIH group were also markedly higher than those in control group (P<0.05). Serum vaspin concentration was significantly correlated with FPG, FINS, HOMA-IR and TC. The expression of vaspin at mRNA and protein levels in the fat tissue of CIH group was evidently higher than that in control group. The protein levels of p-Akt decreased distinctly in CIH group. CONCLUSION: The levels of FINS, HOMA-IR, SaO2 and vaspin were markedly higher than those in control group, indicating that there was a close relationship between vaspin and insulin resistance in OSAHS.