Shoshiro Okada

学生同士が医療者と患者に扮して病気や薬物治療の説明を行う“学生主体型ロールプレイによる実践的薬物治療教育”「薬理学ロールプレイ」は，薬理学アクティブ・ラーニングの一つである．しかし，これまでは一施設内でのみ実施しており，多職種も含めたより規模を大きくした異なる多施設間においては実施されてこなかった．ところが，2020年度のCOVID-19感染拡大は，旧来の対面講義を中心とした医学部教育のやり方を大きく変える転機となった．なかでもZoom等を活用した遠隔リアルタイム授業は，多施設間で，300名程度の学生であれば同時に一ヵ所に集める必要なく実施できるメリットがある．コロナ禍を奇貨として，異なる多施設間による薬理学ロールプレイの合同教育を実施できるインフラが整ったことになる．我々は全国に先駆けて藤田医科大学と愛知医科大学の2大学合同で薬理学ロールプレイを実施したので，その内容を紹介する．

Domoic acid (DA) is an excitatory amino acid analogue of kainic acid (KA) that acts via activation of glutamate receptors to elicit a rapid and potent excitotoxic response, resulting in neuronal cell death. Recently, DA was shown to elicit reactive oxygen species (ROS) production and induce apoptosis accompanied by activation of p38 mitogen-activated protein kinase (MAPK) in vitro. We have reported that WDR35, a WD-repeat protein, may mediate apoptosis in several animal models. In the present study, we administered DA to rats intraperitoneally, then used liquid chromatography/ion trap tandem mass spectrometry (LC-MS/MS) to identify and quantify DA in the brains of the rats and performed histological examinations of the hippocampus. We further investigated the potential involvement of glutamate receptors, ROS, p38 MAPK, and WDR35 in DA-induced toxicity in vivo.

Background: Bupivacaine-induced neurotoxicity has been shown to occur through apoptosis. Recently, bupivacaine was shown to elicit reactive oxygen species (ROS) production and induce apoptosis accompanied by activation of p38 mitogen-activated protein kinase (MAPK) in a human neuroblastoma cell line. We have reported that WDR35, a WD40-repeat protein, may mediate apoptosis through caspase-3 activation. The present study was undertaken to test whether bupivacaine induces apoptosis in mouse neuroblastoma Neuro2a cells and to determine whether ROS, p38 MAPK, and WDR35 are involved.Results: Our results showed that bupivacaine induced ROS generation and p38 MAPK activation in Neuro2a cells, resulting in apoptosis. Bupivacaine also increased WDR35 expression in a dose- and time-dependent manner. Hydrogen peroxide (H₂O₂) also increased WDR35 expression in Neuro2a cells. Antioxidant (EUK-8) and p38 MAPK inhibitor (SB202190) treatment attenuated the increase in caspase-3 activity, cell death and WDR35 expression induced by bupivacaine or H₂O₂. Although transfection of Neuro2a cells with WDR35 siRNA attenuated the bupivacaine- or H₂O₂-induced increase in expression of WDR35 mRNA and protein, in contrast to our previous studies, it did not inhibit the increase in caspase-3 activity in bupivacaine- or H₂O₂-treated cells.Conclusions: In summary, our results indicated that bupivacaine induced apoptosis in Neuro2a cells. Bupivacaine induced ROS generation and p38 MAPK activation, resulting in an increase in WDR35 expression, in these cells. However, the increase in WDR35 expression may not be essential for the bupivacaine-induced apoptosis in Neuro2a cells. These results may suggest the existence of another mechanism of bupivacaine-induced apoptosis independent from WDR35 expression in Neuro2a cells.