Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Curr Med Sci. 2018 Aug;38(4):704-713. doi: 10.1007/s11596-018-1934-x. Epub 2018 Aug 20.
This study aims to explore the effect and mechanism of Jiao-tai-wan (JTW) on systemic and tissue-specific inflammation and insulin resistance in obesity-resistant (OR) rats with chronic partial sleep deprivation (PSD). OR rats with PSD were orally given JTW and Estazolam for 4 weeks. The amount of food intake and metabolic parameters such as body weight increase rate, fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR) and plasma inflammatory markers were measured. The expression levels of circadian proteins cryptochrome 1 (Cryl) and cryptochrome 2 (Cry2) in hypothalamus, adipose and liver tissues were also determined. Meanwhile, the mRNA expression of inflammatory markers, activity of nuclear factor kappa B (NF-κB) p65 protein, as well as the expression levels of insulin signaling pathway proteins in hypothalamus, adipose and liver tissues were measured. Additionally, cyclic adenosine 3', 5'-monophosphate (cAMP) and activity of vasodilator-stimulated phosphoprotein (VASP) in hypothalamus tissue were measured. JTW significantly decreased the body weight increase rate and food intake, ameliorated systemic inflammation and insulin resistance. JTW effectively ameliorated inflammation and increased PI3K/AKT signaling activation in hypothalamus, adipose and liver. Interestingly, all these changes were associated with the up-regulation of circadian gene Cryl and Cry2 protein expression. We also found that in hypothalamus tissue of PSD rats, down-regulation of Cryl and Cry2 activated cAMP/PKA signaling and then led to inflammation, while JTW inhibited this signaling. These results suggested that JTW has the beneficial effect on ameliorating inflammation and insulin resistance in partially sleep-deprived rats by up-regulating Cry expression.
本研究旨在探讨交泰丸（JTW）对慢性部分睡眠剥夺（PSD）肥胖抵抗（OR）大鼠全身和组织特异性炎症及胰岛素抵抗的作用及机制。PSD OR 大鼠经口给予 JTW 和艾司唑仑 4 周。测量食物摄入量和代谢参数，如体重增长率、空腹血糖（FPG）、空腹胰岛素（FINS）、稳态模型评估-胰岛素抵抗（HOMA-IR）和血浆炎症标志物。还测定了下丘脑、脂肪和肝脏组织中昼夜节律蛋白隐花色素 1（Cry1）和隐花色素 2（Cry2）的表达水平。同时，测定了下丘脑、脂肪和肝脏组织中炎症标志物的 mRNA 表达、核因子 kappa B（NF-κB）p65 蛋白活性以及胰岛素信号通路蛋白的表达水平。此外，还测定了下丘脑组织中环磷酸腺苷（cAMP）和血管扩张刺激磷蛋白（VASP）的活性。JTW 显著降低了体重增长率和食物摄入量，改善了全身炎症和胰岛素抵抗。JTW 有效改善了炎症，并增加了下丘脑、脂肪和肝脏中 PI3K/AKT 信号通路的激活。有趣的是，所有这些变化都与昼夜节律基因 Cry1 和 Cry2 蛋白表达的上调有关。我们还发现，在 PSD 大鼠下丘脑组织中，Cry1 和 Cry2 的下调激活了 cAMP/PKA 信号通路，进而导致炎症，而 JTW 抑制了该信号通路。这些结果表明，JTW 通过上调 Cry 表达，对改善部分睡眠剥夺大鼠的炎症和胰岛素抵抗具有有益作用。
