Effects of chronic cerebral hypoperfusion on cognitive function and intestinal mucosal barrier in rats / 中华行为医学与脑科学杂志

ABSTRACT

Objective:To explore the correlation between cognitive impairment and intestinal mucosal barrier injury in rats after chronic cerebral hypoperfusion(CCH), and to quantitatively analyze the changes in cognitive behavior of experimental rats caused by chronic cerebral hypoperfusion, as well as the expression changes of the intestinal mucosal barrier claudin-1 and osteopontin.Methods:Thirty male SD rats were randomly divided into CCH group ( n=15) and sham operation (SHAM) control group ( n=15). The CCH model was established by permanent ligation of bilateral common carotid arteries.Rats in the SHAM group only separated the common carotid artery without ligation.Four weeks later, open field experiment, object discrimination experiment, and Morris water maze experiment were used to detect the emotional arousal ability, the ability to explore new things, and the ability of spatial learning and memory in rats.HE staining and immunofluorescence experiments were conducted to detect the damage of rat ileum tissue.Western blot was used to detect OPN expression, and ELISA was used to detect serum OPN.SPSS 23.0 and GraphPad 8.0 statistical softwares were used to process the data, and the t-test and repeated measures one-way analysis of variance were used for data analysis. Results:In the open field test, compared with the SHAM group ((28.70±10.70)times, (1 030.45±81.51)cm), the number of standing and total exercise distance of rats in the CCH group ((16.70±7.13)times, (736.64±136.71)cm) were decreased( t=1.59, 4.16, both P<0.05). In the object discrimination experiment, the discrimination index of rats in the CCH group (0.44±0.26) was lower than that of the SHAM group (0.91±0.07, t=-7.76, P<0.05). Morris water maze positioning navigation experiment showed that the group main effect and time main effect were both significant( F=383.36, 153.87, P<0.05). Simple effect analysis showed that, compared with the SHAM group, the escape latency and total swimming distance of rats in CCH group increased( P<0.05). Space exploration experiment showed that, compared with SHAM group ((7.20±1.81)times, (9.96±2.95)s), the number of crossings of rats in CCH group ((3.00±0.82)times) decreased, and the incubation period ((29.70±6.28)s) was prolonged( t=4.65, 7.04, both P<0.05). The intestinal mucosal pathology score of SHAM group ((1.98±0.34)points) was lower than that of the CCH group ((4.52±0.27)points), and the difference was significant( t=18.53, P<0.01). Immunofluorescence experiment showed that, compared with SHAM group (125 028.58±33 077.39), the cumulative optical density of claudin-1 between the intestinal epithelial cells of the CCH group(47 154.50±7 507.29) decreased( t=16.10, P<0.01). Western blot experiment showed that, compared with the SHAM group (0.38±0.11), the expression of OPN in the intestines of the CCH group (1.20±0.95) increased( P<0.05). ELISA experiment showed that, compared with the SHAM group ((3.42±0.66)μg/L), the serum OPN content of the CCH group ((14.92±1.45)μg/L) significantly increased( P<0.05). The degree of cognitive impairment was negatively correlated with intestinal mucosal epithelial claudin-1 expression and serum OPN content( P<0.01). Intestinal mucosal epithelial claudin-1 expression was negatively correlated with serum OPN content ( r=-0.952, P<0.01). Conclusion:CCH may cause obvious cognitive impairment in rats and the destruction of the intestinal mucosal barrier.Serum OPN may be a potential serological marker of CCH-induced cognitive impairment and intestinal mucosal barrier destruction in rats.