α7nAChR ameliorating intestinal inflammation and intestinal barrier damage in rats with ce-rebral infarction by inhibiting MyD88-dependent Zonulin release
Objective:To observe the effect of the α7-type nicotinic acetylcholine receptor(α7nAChR)agonist PNU282987 on intestinal inflammation and intestinal barrier damage in rats with cerebral infarction.Methods:A total of 36 male SD rats were randomly divided into three groups:sham group,middle cerebral artery occlusion(MCAO)group,and PNU282987 group.MCAO group and PNU282987 group were prepared by Longa modified sature-embolus method,and PNU282987 group was intraperitoneally injected with 1 mg/kg PNU282987 for 7 consecutive days.Hematoxylin-eosin(HE)staining was used to observe the pathological changes in intestinal mu-cosa.Enzyme-linked immunosorbent assay(ELISA)was performed to detect the levels of tumor necrosis factor(TNF)-α and interleukin(IL)-6 in colon tissue,and the diamine oxidase(DAO),D-lactate(DLA),endotoxin(ET)levels in serum.The expression of toll-like receptor 2(TLR2)protein in colon tissues was detected by immuno-histochemistry.Western blotting was used to detect the expression of the key tight junction proteins in colon tis-sue,including occlusal proteins(Occludin),closed protein-1(Claudin-1),Zonulin,zona occludens(ZO-1),TLR2,myeloid differentiation factor 88(MyD88),nuclear factor-κB(NF-κB)and phosphorylated NF-κB(p-NF-κB)pro-teins.Results:Compared with the sham group,the MCAO group showed intestinal epithelial desquamation,dis-ordered arrangement of intestinal villi,and inflammatory infiltration in the submucosal layer of the intestine.The levels of DAO,DLA,ET in serum,and TNF-α and IL-6 contents in colon tissue were significantly increased,while the expression of Occludin,Claudin-1,and ZO-1 proteins in colon tissue was significantly decreased,and the expression of Zonulin,TLR2,MyD88,and p-NF-κB proteins was significantly increased(all P＜0.05).Com-pared with the MCAO group,the PNU282987 group showed reduced intestinal epithelial damage,significantly decreased levels of serum DAO,DLA,ET,and TNF-α and IL-6 contents in colon tissue,significantly increased expression of Occludin,Claudin-1,and ZO-1 proteins in colon tissue,and significantly decreased expression of Zonulin,TLR2,MyD88,and p-NF-κB proteins(all P＜0.05).Conclusion:PNU282987 can significantly im-prove intestinal inflammation and intestinal barrier damage in rats with cerebral infarction,and its mechanism may be related to inhibition of TLR2/MyD88/NF-κB signaling pathway.
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