间歇低氧对大鼠肝脏细胞中同源性磷酸酶张力蛋白及磷酸化蛋白激酶B表达的影响

The Effect of Intermittent Hypoxia on Expressions of PTEN and p-AKT in Liver Cells of Rats

目的通过检测间歇低氧大鼠肝脏细胞中同源性磷酸酶张力蛋白(PTEN)及其下游信号分子磷酸化蛋白激酶B(p-AKT)的表达水平,探讨肝脏细胞PTEN、p-AKT在间歇低氧相关胰岛素抵抗中的作用。方法选取健康雄性SD大鼠24只,随机分成3组,即慢性间歇空气对照组(CIA组)、慢性间歇低氧4周组(CIH4组)和慢性间歇低氧8周组(CIH8组)。检测3组大鼠空腹血糖、空腹胰岛素、肝细胞中PTEN及p-AKT的表达,用胰岛素敏感指数(ISI)以及稳态模型胰岛素抵抗指数(HOMA-IR)系统评价胰岛素抵抗。以平均灰度值表示PTEN及p-AKT的蛋白表达量,灰度值越高表示蛋白质表达越少。结果与CIA组比较,CIH4组、CIH8组ISI下降有统计学意义(P<0.05),且CIH8组下降比CIH4组明显(P<0.05);CIH4组、CIH8组HOMA-IR升高有统计学意义(P<0.05),且CIH8组升高较CIH4组明显(P<0.05)。与CIA组比较,CIH4组、CIH8组PTEN蛋白表达量升高有统计学意义(P<0.05);与CIH4组比较,CIH8组PTEN蛋白表达量升高亦有统计学意义(P<0.05)。与CIA组比较,CIH4组、CIH8组p-AKT蛋白表达量下降有统计学意义(P<0.05);与CIH4组比较,CIH8组p-AKT蛋白表达量下降亦有统计学意义(P<0.05)。间歇低氧大鼠肝细胞中PTEN的表达随着ISI的下降和HOMA-IR的升高有显著升高趋势,且随间歇低氧时间的延长而显著性增加;间歇低氧大鼠肝细胞中p-AKT随着ISI的下降和HOMA-IR的升高表达下降,且随着间歇低氧时间的延长而更加明显。结论慢性间歇低氧暴露使大鼠空腹血糖及胰岛素水平升高,发生胰岛素抵抗,并且随着间歇低氧暴露时间的延长,胰岛素抵抗程度加重。间歇低氧大鼠肝细胞PTEN蛋白表达增加,p-AKT蛋白表达减少,且与ISI、HOMA-IR具有明显的相关性,表明该蛋白可能在间歇低氧大鼠胰岛素抵抗的发生机制中发挥重要的作用。

Objective To detect the expression level of phosphate and tension homolog deleted on chromsome ten（PTEN） and its downstream signal molecules phosphorylated protein kinase B （p-AKT） in liver cells of rats during intermittent hypoxia, to investigate the effect of PTEN and p-AKT of liver cells on insulin resistance which intermittent hypoxia is relevant. Methods A total of 24 healthy male SD rats were selected and divided into 3 groups randomly, ie. CIA （chronic intermittent air） group, CIH4 （chronic intermittent hypoxia for 4 weeks） group, and CIH8 （chronic intermittent hypoxia for 8 weeks） group. The fasting blood glucose, fasting insulin, PTEN and p-AKT expressions in the liver cells were detected. The insulin resistance was evaluated systematically by the insulin sensitive index （ISI） and homeostasis model assessment of insulin resistance （HOMA-IR）. Average gray value was used to represent the protein expressions of PTEN and p-AKT. Results Compared with CIA group,the decline of ISI in CIH4 group and CIH8 group was significant （ P 〈 0. 05 ）. Furthermore, the decline in CIH8 group was more significant than that in CIH4 group （ P 〈 0. 05 ）. Compared with CIA group, the rise of HOMA-IR in CIH4 and CIH8 groups was statistically significant （ P 〈 0. 05 ）. In addition, the rise in CIH8 group was more significant than that in CIH4 group （ P 〈 0. 05 ）. Compared with CIA group, there was a significant rise in the protein expressions of PTEN in CIH4 and CIH8 groups （ P 〈 0. 05 ）. Compared with CIH4 group, the rise of the protein expressions of PTEN in CIH8 group was still statistically significant （ P 〈 0. 05 ）. Compared with CIA group, there was a significant decline in the protein expressions of p-AKT in CIH4 and CIH8 groups （ P 〈 0. 05 ）. Compared with CIH4 group, the decline of protein expression of p-AKT in CIH8 group was still of statistical significance （ P 〈 0. 05 ）. There was a significantly increasing trend for the expression of PTEN in the liver cells of rats with intermittent hypoxia along with the decline of ISI and rise of HOMA-IR. The expression increased significantly with the longer duration of intermittent hypoxia. The expression of p-AKT in liver cells of rats with intermittent hypoxia decreased along with the decline of ISI and rise of HOMA-IR. Furthermore, the decline tendency was more significant with the long duration of intermittent hypoxia. Conclusions The fasting blood glucose of rats and insulin level increase due to the chronic intermittent hypoxia, resulting in the insulin resistance. The degree of insulin resistance increases with the longer duration of intermittent hypoxia. The expression of PTEN protein increases with intermittent hypoxia, and that of p-AKT protein decreases, which is obviously correlated with ISI and HOMA-IR. It is indicated that the PTEN protein possibly play an important role in the mechanism of insulin resistance for rats with intermittent hypoxia.