Huang Hui-Chun, Tsai Ming-Hung, Lee Fa-Yauh, Lin Te-Yueh, Chang Ching-Chih, Chuang Chiao-Lin, Hsu Shao-Jung, Hou Ming-Chih, Huang Yi-Hsiang
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei 100, Taiwan.
Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
Pharmaceutics. 2020 Apr 28;12(5):403. doi: 10.3390/pharmaceutics12050403.
Non-alcoholic fatty liver disease (NAFLD) is linked with metabolic syndrome. Previous studies showed that obesity may disrupt adrenal function and adversely affect its counter-regulations against shock. This study hence evaluated adrenal function abnormalities in NAFLD with shock.
Sprague-Dawley rats were fed with regular chow-diet (control) or high fat diet (HFD, 60% energy derived from fat). Blood tests were performed at the end of the 4th, 6th and 8th week, respectively. Experiments were performed at the end of the 8th week.
HFD rats developed NAFLD. HFD rats had 27% and 51% increase in plasma corticosterone at the 6th and 8th week in usual status. However, HFD rats had 5 times more reduction of mean arterial pressure in response to lipopolysaccharide-induced sepsis as compared to control rats. The corticosterone increment ratio was also lower in HFD rats, even after ACTH administration. 11β-HSD system tended to generate more corticosterone in HFD rats under hemodynamic stable status without shock and the trend was lost in HFD rats with septic shock.
Rats with NAFLD had profound septic shock due to inadequate corticosterone response. This is, at least partly, due to 11β-HSDs dysregulation in sepsis.
非酒精性脂肪性肝病（NAFLD）与代谢综合征相关。既往研究表明，肥胖可能会扰乱肾上腺功能，并对其抗休克的反调节产生不利影响。因此，本研究评估了合并休克的NAFLD患者的肾上腺功能异常情况。
将斯普拉格-道利大鼠分为正常饮食组（对照组）和高脂饮食组（HFD，60%的能量来自脂肪）。分别在第4、6和8周结束时进行血液检测。实验在第8周结束时进行。
HFD组大鼠发生了NAFLD。在正常状态下，HFD组大鼠在第6周和第8周时血浆皮质酮分别增加了27%和51%。然而，与对照组大鼠相比，HFD组大鼠对脂多糖诱导的脓毒症的平均动脉压降低幅度高出5倍。即使在给予促肾上腺皮质激素后，HFD组大鼠的皮质酮增加率也较低。在无休克的血流动力学稳定状态下，HFD组大鼠的11β-羟类固醇脱氢酶（11β-HSD）系统倾向于产生更多的皮质酮，而在脓毒性休克的HFD组大鼠中这种趋势消失。
NAFLD大鼠因皮质酮反应不足而发生严重的脓毒性休克。这至少部分是由于脓毒症中11β-HSD的失调所致。
