Chang Cheng, Bai Wenya, Li Junjie, Huo Siying, Wang Tinghua, Shao Jianlin
Department of Anesthesiology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China.
Department of anesthesiology, The first people's hospital of huaihua, huaihua, Hunan Province, China.
Curr Ther Res Clin Exp. 2023 Jan 18;98:100691. doi: 10.1016/j.curtheres.2023.100691. eCollection 2023.
Although controversial, experimental data suggest the use of propofol may be associated with neurotoxicity. The mechanisms responsible for propofol neurotoxicity in animals are not yet clear.
This study aimed to determine the effects of propofol on the proliferation of neural stem cells in rat hippocampus and the mechanisms underlying these effects.
Forty-five adult male Sprague-Dawley rats were randomly divided into 5 groups: Control (N group), intralipid (V group), 30 mg/kg propofol (Prop30 group), 60 mg/kg propofol (Prop60 group), and 120 mg/kg propofol (Prop120 group). The rats in all groups received 5, once daily intraperitoneal injections. For each of the 5 days, the N group received 6 mL/kg normal saline, the V group received 6 mL/kg fat emulsion, the Prop30 group received 30 mg/kg propofol, the Prop60 group received 60 mg/kg propofol, and the Prop120 group received 120 mg/kg propofol. Memory function was scored daily using the Morris water maze test. Immunofluorescence staining was used to histologically monitor the proliferation and differentiation of the rats' hippocampal neural stem cells, and real time quantitative polymerase chain reaction and Western blotting were used to determine the expression of Notch3, Hes1, and Hes5.
Compared with the N group, the Prop120 group exhibited reduced learning and memory, whereas there were no significant differences for the Prop60 group. The number of β-tubulin III cells increased in the Prop60 group, but decreased in the Prop120 group. Compared with the N group, the relative expression of Notch3 and Hes5 increased significantly in the Prop60 group, whereas this expression decreased in the Prop120 group.
These data demonstrate that repeated, subchronic (5 days) intraperitoneal injections of 60 mg/kg propofol can effectively promote rat hippocampal neural stem cells proliferation and differentiation, and that this is likely mediated by its effects on the Notch3-Hes5 pathway.
尽管存在争议，但实验数据表明丙泊酚的使用可能与神经毒性有关。丙泊酚在动物中引起神经毒性的机制尚不清楚。
本研究旨在确定丙泊酚对大鼠海马神经干细胞增殖的影响及其潜在机制。
将45只成年雄性Sprague-Dawley大鼠随机分为5组：对照组（N组）、脂质乳剂组（V组）、30mg/kg丙泊酚组（Prop30组）、60mg/kg丙泊酚组（Prop60组）和120mg/kg丙泊酚组（Prop120组）。所有组大鼠均每日腹腔注射1次，连续注射5天。在这5天中的每一天，N组大鼠接受6mL/kg生理盐水，V组大鼠接受6mL/kg脂肪乳剂，Prop30组大鼠接受30mg/kg丙泊酚，Prop60组大鼠接受60mg/kg丙泊酚，Prop120组大鼠接受120mg/kg丙泊酚。每天使用Morris水迷宫试验对记忆功能进行评分。采用免疫荧光染色对大鼠海马神经干细胞的增殖和分化进行组织学监测，采用实时定量聚合酶链反应和蛋白质印迹法检测Notch3、Hes1和Hes5的表达。
与N组相比，Prop120组大鼠学习记忆能力下降，而Prop60组无显著差异。Prop60组β-微管蛋白III阳性细胞数量增加，而Prop120组减少。与N组相比，Prop60组Notch3和Hes5的相对表达显著增加，而Prop120组则降低。
这些数据表明，连续5天腹腔注射60mg/kg丙泊酚可有效促进大鼠海马神经干细胞的增殖和分化，这可能是通过其对Notch3-Hes5信号通路的作用介导的。
