Department of Clinical Nutrition, Affiliated Hospital, Qingdao University, Qingdao, China.
Center for Medical Research, Affiliated Hospital, Qingdao University, Qingdao, China.
Clin Exp Pharmacol Physiol. 2020 Jan;47(1):67-75. doi: 10.1111/1440-1681.13136. Epub 2019 Oct 8.
It is known that 7,8-dihydroxyflavone (7,8-DHF), a synthetic agonist specific for TrkB, promotes intestinal cholinergic contraction. However, after intestinal ischaemia-reperfusion (IR) injury, how 7,8-DHF affects intestinal contractile dynamics is unknown. In this study, an IR injury model was prepared with rats subjected to 45 minutes clamping of the superior mesenteric artery. The IR injury decreased postoperative food intake and body weight, delayed defecation time, lowered intestinal propulsive rate and decreased cholinergic contraction of jejunal muscle strips, indicating the occurrence of injured jejunal contraction after IR. Feeding rats with 7,8-DHF improved these intestinal activities injured by IR, which exhibited the in vivo effect of 7,8-DHF. To explore its molecular mechanism, the expression and phosphorylation of TrkB, PLC γ1, Akt, and ERK1/2 in the jejunal strips were examined with western blots. The IR injury significantly decreased the expression and phosphorylation levels of all factors studied here. However, 7,8-DHF feeding specifically enhanced the phosphorylation of TrkB, PLC γ1 and Akt factors in both sham- and IR-operated rats, indicating that 7,8-DHF may have activated TrkB which then activated its downstream PLC γ1 and Akt. Finally, we found that 7,8-DHF augmented cholinergic receptor M3 expression somehow. These results imply a possibility that 7,8-DHF might be capable of alleviating the jejunal contractile damage caused by IR through activation of TrkB and augmentation of M3 expression.
已知 7,8-二羟基黄酮（7,8-DHF）是一种针对 TrkB 的合成激动剂，可促进肠道胆碱能收缩。然而，在肠缺血再灌注（IR）损伤后，7,8-DHF 如何影响肠道收缩动力学尚不清楚。在这项研究中，使用肠系膜上动脉夹闭 45 分钟的大鼠制备 IR 损伤模型。IR 损伤降低了术后采食量和体重，延迟了排便时间，降低了肠道推进率，减少了空肠肌条的胆碱能收缩，表明 IR 后发生了受损的空肠收缩。用 7,8-DHF 喂养大鼠可改善 IR 损伤的这些肠道活动，这表现出 7,8-DHF 的体内作用。为了探讨其分子机制，用 Western blot 法检测了空肠肌条中 TrkB、PLCγ1、Akt 和 ERK1/2 的表达和磷酸化。IR 损伤显著降低了所有研究因素的表达和磷酸化水平。然而，7,8-DHF 喂养特异性增强了 sham 和 IR 操作的大鼠中 TrkB、PLCγ1 和 Akt 因子的磷酸化，表明 7,8-DHF 可能已激活了 TrkB，随后激活了其下游 PLCγ1 和 Akt。最后，我们发现 7,8-DHF 以某种方式增强了胆碱能受体 M3 的表达。这些结果表明，7,8-DHF 可能通过激活 TrkB 和增强 M3 表达来缓解 IR 引起的空肠收缩损伤。
