Sodium butyrate preconditioning improves cognitive impairment in-duced by intestinal ischemia/reperfusion by reducing blood-brain barrier damage in rats
10.12092/j.issn.1009-2501.2024.06.005
- VernacularTitle:丁酸钠预处理通过减轻血脑屏障损伤改善大鼠肠缺血再灌注诱导的认知障碍
- Author:
Lu CAO
1
;
Yingbin WANG
;
Wei ZHANG
;
Yan LIU
;
Li ZHANG
;
Jingyu ZHANG
Author Information
1. 兰州大学第二临床医学院,兰州 730030,甘肃
- Keywords:
sodium butyrate;
blood-brain barri-er;
intestinal ischemia-reperfusion;
cognitive dys-function
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2024;29(6):637-644
- CountryChina
- Language:Chinese
-
Abstract:
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.
