丙泊酚对SD乳鼠少突胶质细胞髓鞘碱性蛋白表达和髓鞘形成的影响

Effect of propofol on myelin basic protein expression and myelination of oligodendrocytes in neonatal SD rats

目的探讨不同剂量丙泊酚对新生SD乳鼠少突胶质细胞合成髓鞘碱性蛋白(MBP)和大脑髓鞘形成的影响。方法出生后7 d(P7)SD乳鼠57只,随机分为对照组(n=13)、溶剂脂肪乳组(n=5)、25、50和100 mg/kg丙泊酚组(各组n=13),单次腹腔注射给药。采用qPCR和Western blot检测注药后8 h mbp mRNA、caspase-3 mRNA和MBP、Cleaved Caspase-3蛋白的表达;免疫荧光法检测注药后8 h少突胶质细胞凋亡以及24 h大脑胼胝体和内囊处髓鞘形成情况。结果与对照组相比,各丙泊酚组8 h mbp mRNA和MBP蛋白呈剂量依赖性下调(P<0.05),caspase-3 mRNA和Cleaved Caspase-3蛋白转录表达水平均呈剂量依赖性增加(P<0.05);同时少突胶质细胞凋亡明显增加,且50和100 mg/kg组较25 mg/kg组凋亡显著增多(P<0.05);24 h胼胝体处100 mg/kg丙泊酚组、内囊处50和100 mg/kg丙泊酚组髓鞘形成均明显减少(P<0.05)。结论丙泊酚可致SD乳鼠少突胶质细胞呈剂量依赖性凋亡增加,MBP表达减少,并且不同程度的影响胼胝体和内囊处髓鞘的形成。

Objective To investigate the effects of different doses of propofol on myelin basic protein(MBP) synthesis and myelination of oligodendrocytes in neonatal SD rats. Methods A total of 57 neonatal SD rats(7 days old) were randomly divided into control group(n=13), vehicle(fat emulsion) group(n=5), and 25, 50 and 100 mg/kg propofol groups(n=13 in each group). Eight hours after a single intraperitoneal injection of propofol or the vehicle, the rats were examined for expressions of mbp mRNA, caspase-3 mRNA, cleaved caspase-3 and MBP in the brain tissues using qPCR and Western blotting.Immunofluorescence assay was used to detect the apoptosis of the oligodendrocytes at 8 h after the injection and the myelination of the corpus callosum and internal capsule at 24 h. Results Compared with the control group, the neonatal rats with propofol injections showed significantly down-regulated expressions of mbp mRNA and MBP protein in the brain tissue(P<0.05). Propofol dose-dependently increased the transcription level of caspase-3 and the protein levels of cleaved caspase-3 at 8 h after the injection(P<0.05). Propofol injection significantly increased the apoptosis of the oligodendrocytes, and the effect was significantly stronger in 50 and 100 mg/kg groups than in 25 mg/kg group(P<0.05). At 24 h after propofol injection, myelin formation was significantly decreased in the corpus callosum of the neonatal rats in 100 mg/kg propofol group and in the internal capsule in 50 and 100 mg/kg groups(P<0.05). Conclusion In neonatal SD rats, propofol can dose-dependently promote oligodendrocyte apoptosis, decrease MBP expressions in the brain, and suppress myelin formation in the corpus callosum and the internal capsule.