Effects of propofol on inflammatory responses in substantia nigra in mice with Parkinson′s disease: relationship with α-syn expression / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effects of propofol on inflammatory responses in substantia nigra in mice with Parkinson′s disease (PD) and its relationship with α-synuclein (α-syn) expression.Methods:Thirty-three SPF healthy male C57BL/6 mice, aged 12 weeks, weighing 24-26 g, were divided into 3 groups ( n=11 each) using a random number table method: control group (group Con), group PD and propofol group (group Pro). In PD and Pro groups, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) 30 mg/kg was intraperitoneally injected once a day for 5 consecutive days to induce PD.Propofol 50 mg/kg was intraperitoneally injected at 2 h after the last injection of MPTP in group Pro, while the equal volume of normal saline was given instead in Con and PD groups.The rotarod test was performed at 24 h after administration.The animals were then sacrificed and substantia nigra was removed for determination of contents of interleukin-1β (IL-1β) and tumor necrosis factor (TNF)-α (by enzyme-linked immunosorbent assay), the expression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and p-caspase-1 (by Western blot) and the expression of α-syn (by immunofluorescence staining). Results:Compared with Con group, the first fall-off time was significantly shortened, the number of falling off was increased, the contents of IL-1β and TNF-α were increased, and the expression NLRP3, p-caspase-1and α-syn was up-regulated in substantia nigra in group PD ( P<0.05). Compared with PD group, the first fall-off time was significantly prolonged, the number of falling off was decreased, the contents of IL-1β and TNF-α were decreased, and the expression NLRP3, p-caspase-1and α-syn was down-regulated in substantia nigra in group Pro ( P<0.05). Conclusion:Propofol can improve behaviors of the mice through inhibiting inflammatory responses in substantia nigra, and the mechanism is related to down-regulating the expression of α-syn.