Kim Young Sung, Kim Woon Young, Kim Yeon-Hwa, Yoo Ji Won, Min Too Jae
Department of Anesthesiology, Korea University College of Medicine, Seoul, Korea.
Department of Anesthesiology and Pain Medicine, Korea University Ansan Hospital, 123, Jeokgeum-ro, Danwon-gu, Ansan-si, Gyeonggi-do 15355 Korea.
Springerplus. 2016 May 12;5:610. doi: 10.1186/s40064-016-2281-7. eCollection 2016.
Ischemic insults during operation can cause ischemic-reperfusion injuries in brain as well as memory impairments. Total intravenous anesthesia (TIVA) is the preferred anesthetic method in brain surgery, as it utilizes motor evoked potential monitoring. And the use of opioids is common in TIVA. However there are few studies about ischemic protective effect of opioids to glial cells.
We used mixed cultures of rat glial cells, which were harvested from the brain of 1-day old rat. We divided the experimental groups according to their hydromorphone conditioning period: (a) pre-culture, (b) per-culture, or (c) pre- and per-culture. We measured the levels of the reactive oxygen species (ROS) induced by tert-butyl hydroperoxide (TBH) using flow cytometry. The ROS levels in the glial cells were also measured after the administration of 100 nM hydromorphone and selective opioid receptor antagonists.
The ROS levels were reduced in the hydromorphone-treated group, as compared to the control group (only TBH treated). There were no differences between pre-conditioned and per-conditioned groups. However, the ROS levels were more reduced in pre- and per-conditioned group compared to pre-conditioned or per-conditioned only groups. Furthermore, selective antagonists for the delta, kappa, or mu opioid receptor partially negated the hydromorphone effect.
This study demonstrated that hydromorphone can have additional protective effects on oxidative stress when pre- and per-conditioning is combined. Furthermore we proved that μ, δ, κ opioid receptors participate in protective mechanism of hydromorphone to glial cells.
手术期间的缺血性损伤可导致脑缺血再灌注损伤以及记忆障碍。全凭静脉麻醉（TIVA）是脑外科手术中首选的麻醉方法，因为它利用运动诱发电位监测。并且阿片类药物在TIVA中使用普遍。然而，关于阿片类药物对神经胶质细胞的缺血保护作用的研究很少。
我们使用从1日龄大鼠脑中收获的大鼠神经胶质细胞混合培养物。我们根据氢吗啡酮预处理时间将实验组分为：（a）预培养，（b）共培养，或（c）预培养和共培养。我们使用流式细胞术测量叔丁基过氧化氢（TBH）诱导的活性氧（ROS）水平。在给予100 nM氢吗啡酮和选择性阿片受体拮抗剂后，也测量神经胶质细胞中的ROS水平。
与对照组（仅用TBH处理）相比，氢吗啡酮处理组的ROS水平降低。预处理组和共处理组之间没有差异。然而，与仅预处理或仅共处理组相比，预培养和共培养组的ROS水平降低得更多。此外，δ、κ或μ阿片受体的选择性拮抗剂部分抵消了氢吗啡酮的作用。
本研究表明，当预培养和共培养相结合时，氢吗啡酮对氧化应激可具有额外的保护作用。此外，我们证明了μ、δ、κ阿片受体参与了氢吗啡酮对神经胶质细胞的保护机制。
