ABSTRACT
Objective:To investigate the effect and mechanism of non-selective histone deacetylase (HDAC) inhibitor sodium butyrate (NaB) on neuropathic pain and pain-induced memory impairment in mice.Methods:Forty clean grade male C57BL/6J mice were were divided into 4 groups by random number table method ( n=10 in each group): sham + saline, sham + NaB, chronic constriction injury (CCI)+ saline and CCI + NaB.The mouse CCI model was established by sciatic nerve ligation. Non-selective HDAC inhibitors NaB(300 mg/kg) was intraperitoneally injected into the mice in Sham+ NaB group and CCI+ NaB group once a day 15-28 days after modeling, while the mice in Sham+ saline group and CCI+ saline group were intraperitoneally injected with the same volume of saline. On the 14th and 28th day after operation, the athletic ability was measured by open field test (OFT), the pain behavior was measured by paw withdrawal threshold (PWT) and paw withdrawal latency (PWL), and the memory function was measured by Y-maze. After the behavioral experiment, hippocampus and spinal dorsal horn tissues were taken for the activity of HDAC measurement, and hippocampus tissues were taken for the expression levels of BDNF and PSD95 measurement. SPSS 25.0 software was used for statistical analysis. The data were compared by repeated measurement ANOVA and one-way ANOVA. Results:After treatment with NaB, the interaction effects of the accuracy of spontaneous alternation of PWT, PWL and Y maze in mice were significant( F=21.07, 6.98, 7.79, all P<0.05). Compared with the Sham + saline group, the PWT((0.83±0.30)g, (0.25±0.22)g, (0.24±0.11)g; both P<0.05), the PWL((14.97±4.02)s, (5.99±1.51)s, (6.87±0.90)s; both P<0.05) and the spontaneous alternation in Y maze(71.57±2.80)%, (56.96±0.60)%, (62.86±4.94)%; both P<0.05) in CCI+ Saline group and CCI+ NaB group were lower. After treatment with NaB, compared with CCI + saline group, PWT((0.22±0.13)g, (0.62±0.23)g; P<0.05), PWL((5.62±2.00)s, (8.82±2.13)s; P<0.05)and the accuracy of spontaneous alternation of Y maze were significantly higher ((56.54±7.50)%, (66.35±8.20)%; P<0.05), the HDAC activity in hippocampus((173.40±7.38)%, (122.70±8.40)%; P<0.05)and in spinal cord ((153.40±10.58)%, (111.40±11.40)%; P<0.05)were significantly lower, and the expression of BDNF((0.65±0.06), (0.87±0.43); P<0.05)and PSD95((0.70±0.40), (0.87±0.04); P<0.05)were significantly higher in CCI + NaB group. Conclusion:NaB can improve neuropathic pain and pain-induced memory impairment.The mechanism may be related to the inhibition of HDAC activity and the up-regulation of BDNF and PSD95 expression in hippocampus.
ABSTRACT
Objective:To compare the choriocapillaris flow density and choroidal vessel volume (CVV) of acute and chronic central serous chorioretinopathy (CSC).Methods:A cross-sectional observational clinical study. A total of 64 eyes of 64 patients (CSC group) diagnosed with CSC at Department of Ophthalmology of West China Hospital of Sichuan University from May 2019 to October 2020, and a total of 64 eyes of 64 age and gender matched healthy volunteers (control group) during the same period were included in this study. In the CSC group, there were 34 patients with acute CSC (acute CSC group) and 30 patients with chronic CSC (chronic CSC group). There was no significant difference in age ( t=-0.041) and sex composition ratio ( χ2=0.191) between CSC group and control group ( P>0.05). There were statistically significant differences in age ( t=-1.872) and sex composition ratio ( χ2=8.778) between acute CSC group and chronic CSC group( P<0.05). Swept source optical coherence tomography angiography (SS-OCTA) was performed using VG200D. The scanning mode was 512×512 and scannig range was 12 mm × 12 mm. The choriocapillaris flow density of the 3 mm, 6 mm, 12 mm circular area and 1-3 mm ring, 3-6 mm ring, and 6-12 mm ring, and the CVV of the of the 3 mm, 6 mm, 12 mm circular area was automatically generated by the built-in software (v1.28.6). The age, choriocapillaris flow density and CVV were compared between two groups using independent sample t test. Results:Compared with the control group, the choriocapillaris flow density decreased in the CSC group, and there were statistically significant differences in the 3 mm, 6 mm circular area ( t=-7.210, -4.040; P<0.001). There were statistically significant differences between CSC group and control group in the 3 mm, 6 mm, 12 mm circular area ( t=1.460, 12.270, 11.250; P<0.05). Compared with the acute CSC group, the choriocapillaris flow density decreased in the chronic CSC group, and there were statistically significant differences ( P<0.05) in the 3 mm, 6 mm circular area ( t=3.230, 2.330), the total and four quadrants of 1-3 mm ring ( t=2.780, 2.060, 2.140, 2.620, 3.770), the superior quadrants of the 3-6 mm ring ( t=2.550), and the superior and temporal of 6-12 mm ring ( t=3.070, 2.610). There was no significant difference of CVV in the 3 mm, 6 mm and 12 mm circular area between the acute CSC group and the chronic CSC group ( t=0.250, 0.070, -0.110; P>0.05). Conclusion:Compared with acute CSC, chronic CSC exhibits significant decreased choriocapillaris flow density and no change in CVV.