Activated A7nachr Improves Postoperative Cognitive Dysfunction and Intestinal Injury Induced by Cardiopulmonary Bypass in Rats: Inhibition of the Proinflammatory Response Through the Th17 Immune Response

作者：Chen, Keyan; Sun, YingJie; Dong, Wanwei; Zhang, Tiezheng; Zhou, Nan; Yu, Weiwei; Diao, Yugang; Guo, Shanbin^*; Tian, Yue^*

来源：Cellular Physiology and Biochemistry, 2018, 46(3): 1175-1188.

DOI：10.1159/000489068

• A7nachr
• Cardiopulmonary Bypass
• Postoperative Cognitive Dysfunction
• Intestinal Injury
• Th17

Backgrund/Aims: To investigate the effects of activated alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) on postoperative cognitive dysPOCD) and intestinal injury induced by cardiopulmonary bypass (CPB) and its relationship with the Th17 response in order to provide a theoretical basis for organ protection and targeted drug therapy during the perioperative period. Methods: Sprague-Dawley rat models of CPB were established. Rat intestinal and brain injuries were observed after CPB using hematoxylin and eosin staining. Cell apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling. Inflammatory factors and markers of brain injury in rat serum were measured using enzyme-linked immunosorbent assay. The expression levels of Bcl-2, Bax, caspase-3, ZO-1, occludin, AQP4, ROR gamma T, and alpha 7nAchR were examined using western blotting. Transcription factor ROR.T expression was determined using real-time fluorescent quantitative polymerase chain reaction. Th17 cells in the peripheral blood and spleen were determined using flow cytometry. alpha 7nAchR knockout rats were established. The Th17 response in the peripheral blood and spleen of alpha 7nAchR knockout rats was further verified using flow cytometry. Results: CPB can induce POCD and intestinal injury in rats. alpha 7nAchR activation markedly reduced intestinal injury, POCD, neuronal apoptosis, proinflammatory factor expression, and number of CD4(+)IL-17(+) cells. alpha 7nAchR knockout significantly increased serum D-lactic acid, FABP2, S-100 beta, NSE, TNF-alpha, IL-6, and IL-17 secretion. The number of CD4(+)IL-17(+) cells was also significantly increased. Conclusion: alpha 7nAchR activation markedly ameliorates the intestinal injury and POCD induced by CPB. Inhibition of the Th17 immune response can reduce the proinflammatory response, which could provide a new method for clinical perioperative organ protection and targeted drug therapy.

• 出版日期2018
• 单位中国医科大学; 中国人民解放军沈阳军区总医院