Dandan Xing1, Rui Zhang1, Shun Li1, Pinjie Huang1, Chenfang Luo1, Ziqing Hei1, Zhengyuan Xia2, Xiaoliang Gan3. 1. Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 2. Department of Anesthesiology, University of Hong Kong, Hong Kong, China. 3. Department of Anesthesiology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. Electronic address: ganxiaoliang@yeah.net.
Abstract
AIM OF THE STUDY: Mast cell (MC) degranulation contributes to the protection mediated by ischemic preconditioning (IPC); however, the precise mechanisms underlying this protection remain largely unknown. Mast cell carboxypeptidase A (MC-CPA) is released solely from MCs and plays a critical role in degrading toxins and endothelin 1 (ET-1). The present study sought to explore whether MC-CPA is involved in the process of IPC in a rodent model of small intestinal ischemia reperfusion (IIR) injury. MATERIALS AND METHODS: IIR injuries were induced in Sprague-Dawley rats by clamping the superior mesenteric artery for 60 min followed by reperfusion for 2 h. One cycle of 10 min intestinal ischemia and 10 min of reperfusion was used in the IPC group, and the MC stabilizer cromolyn sodium and MC potato carboxypeptidase inhibitor were administered before the start of IPC. At the end of experiment, intestine tissue was obtained for assays of the MC-CPA3, tumor necrosis factor-α, interleukin-6, and ET-1 contents and myeloperoxidase activities. Intestinal histologic injury scores and MC degranulation were assessed. Apoptosis indices and cleaved caspase- 3 protein expressions were quantified. RESULTS: IIR resulted in severe injury, as evidenced by significant increases in injury scores and MC-CPA3, tumor necrosis factor-α, interleukin-6, and ET-1 contents that were accompanied with concomitant elevations in cleaved caspase 3 expression, apoptosis indices, and myeloperoxidase activities. IPC induced a significant increase in MC-CPA3, induced MC degranulation, and attenuated IIR injury by downregulating IIR-induced biochemical changes, whereas cromolyn sodium and potato carboxypeptidase inhibitor abolished the IPC-mediated changes. CONCLUSIONS: These data suggest that IPC protected against IIR injury via the MC degranulation-mediated release of MC-CPA.
AIM OF THE STUDY: Mast cell (MC) degranulation contributes to the protection mediated by ischemic preconditioning (IPC); however, the precise mechanisms underlying this protection remain largely unknown. Mast cell carboxypeptidase A (MC-CPA) is released solely from MCs and plays a critical role in degrading toxins and endothelin 1 (ET-1). The present study sought to explore whether MC-CPA is involved in the process of IPC in a rodent model of small intestinal ischemia reperfusion (IIR) injury. MATERIALS AND METHODS: IIR injuries were induced in Sprague-Dawley rats by clamping the superior mesenteric artery for 60 min followed by reperfusion for 2 h. One cycle of 10 min intestinal ischemia and 10 min of reperfusion was used in the IPC group, and the MC stabilizer cromolyn sodium and MC potato carboxypeptidase inhibitor were administered before the start of IPC. At the end of experiment, intestine tissue was obtained for assays of the MC-CPA3, tumor necrosis factor-α, interleukin-6, and ET-1 contents and myeloperoxidase activities. Intestinal histologic injury scores and MC degranulation were assessed. Apoptosis indices and cleaved caspase- 3 protein expressions were quantified. RESULTS: IIR resulted in severe injury, as evidenced by significant increases in injury scores and MC-CPA3, tumor necrosis factor-α, interleukin-6, and ET-1 contents that were accompanied with concomitant elevations in cleaved caspase 3 expression, apoptosis indices, and myeloperoxidase activities. IPC induced a significant increase in MC-CPA3, induced MC degranulation, and attenuated IIR injury by downregulating IIR-induced biochemical changes, whereas cromolyn sodium and potato carboxypeptidase inhibitor abolished the IPC-mediated changes. CONCLUSIONS: These data suggest that IPC protected against IIR injury via the MC degranulation-mediated release of MC-CPA.
Authors: Dmitri Atiakshin; Andrey Kostin; Ivan Trotsenko; Vera Samoilova; Igor Buchwalow; Markus Tiemann Journal: Cells Date: 2022-02-06 Impact factor: 6.600