Sodium butyrate preconditioning improves cognitive impairment in-duced by intestinal ischemia/reperfusion by reducing blood-brain barrier damage in rats
AIM:To investigate the possible mech-anisms by observing the effects of sodium butyrate on the blood-brain barrier and cognitive function after intestinal ischemia/reperfusion in rats.METH-ODS:SD rats were randomly divided into 4 groups of 12 rats each,(1)sham-operated group(the Sham group);(2)intestinal ischemia/reperfusion group(the Ⅱ/R group);(3)intestinal ischemia/re-perfusion+sodium butyrate group(the NaB group):gavage of NaB 500 mg·kg-1·d-1 for 1 week before modeling;(4)intestinal ischemia/reperfusion+sodi-um butyrate+ITSA-1 group(the ITSA-1 group):NaB 500 mg·kg-1·d-1 gavage 1 week before modeling+IT-SA-1 0.5 mg/kg intraperitoneal injection in the first 5 d,3 d and 1 d.Intestinal mucosal injury was eval-uated by HE staining.Morris water maze test evalu-ated the cognitive function of rats.The microstruc-ture of the blood-brain barrier was observed by transmission electron microscope.The levels of in-flammatory cytokines IL-1β,IL-6,TNF-α,Claudin5,ZO-1,and MMP-9 in brain tissue were detected by ELISA.Western blotting detected Claudin5,ZO-1,CypA,and MMP-9 levels.RESULTS:Compared with the Sham group,Chiu's score in the Ⅱ/R group was increased(P<0.001).The swimming distance was increased(P<0.05),the proportion of the non-plat-form quadrant was increased(P<0.001),and the in-cubation period was prolonged(P<0.05).The micro-structure of the blood-brain barrier was changed under the transmission electron microscope.The inflammatory cytokines IL-1β,IL-6,and TNF-α were increased(P<0.001),the expressions of CypA and MMP-9 were increased(P<0.01),and the expres-sions of Claudin5 and ZO-1 were decreased(P<0.01,P<0.001).Compared with the Ⅱ/R group,neu-roinflammation,and blood-brain barrier damage were reduced,and cognitive function was im-proved in the Ⅱ/R+NaB group.The above injuries in group Ⅱ/R+NaB+ITSA-1 were similar to those in group Ⅱ/R.CONCLUSION:Sodium butyrate can ameliorate Ⅱ/R-induced neurocognitive dysfunction in rats by alleviating blood-brain barrier damage,possibly related to inhibiting the CypA/MMP-9 pathway.
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