Protective effect of human bone marrow mesenchymal stem cells modified with BACE-1 on brain tissue of rats with traumatic brain injury
Tian Qing
Lin Yun
Chen Yiying
Wu Zhengzhen
Abstract：Objective To explore the protective effect of human bone marrow mesenchymal stemcells(BMSCs)modifiedwithβ-siteamyloidprecursorproteincleavageenzyme-1(BACE-1)on brain tissue in the rats with traumatic brain injury(TBI).Methods BMSCs were infected with adenovirus of knockdown BACE-1 gene and empty vector adenovirus,and green fluorescence and BACE-1 expression were detected.One hundred rats were randomly divided into Sham group,TBI group,BMSCs infected with adenovirus of knockdown BACE-1 gene group(Ad-si-BACE-1-BMSCs)and BMSCs infected with empty vector adenovirus group(Ad-BMSCs),with twenty-five rats in each group.TBI rat models were established by Marmarou′s free fall method,and Sham group only underwent craniotomy without injury.After 2 hours of modeling,Ad-si-BACE-1-BMSCs group and Ad-BMSCs group were injected with BMSCs infected with adenovirus of knockdown BACE-1 gene and empty vector adenovirus through the tail vein,respectively.Sham group and TBI group were both given equal volumes of physiological saline.After 7 days of BMSCs transplantation,Morris water maze experiment was used to detect the cognitive ability of rats;Hematoxylin-eosin staining and Nissl staining were used to evaluate hippocampal tissue damage in rats;TUNEL staining was used to detect hippocampal neuronal apoptosis;Thioflavin-S staining and immunohistochemistry staining were used to detect β-amyloid protein(Aβ)content in hippocampus tissue;Malondialdehyde(MDA)and superoxide dismutase(SOD)levels in hippocampus tissue were detected by thiobarbituric acid test and automatic biochemical analyzer.Immunofluorescence staining was used to detect ionized calcium binding adapter molecule 1(Iba-1)+ tumor necrosis factor-α(TNF-α)+,Iba-1+ interleukin(IL)-6+,Iba-1+IL-1β+,glial fibrillary acidic protein(GFAP)+TNF-α+,GFAP+IL-6+,GFAP+IL-1β+;Western blot was used to detect BACE-1,Aβ,TNF-α,IL-6 and IL-1β levels.Results Compared with Sham group,escape latency was increased,the number of platform crossing and the time of platform stay were decreased,the hippocampal neurons arrangement was disordered,Nissl body was decreased,TUNEL positive rate was increased,Aβ,BACE-1,TNF-α,IL-6,IL-1β protein,MDA content,Iba-1+TNF-α +,Iba-1+ IL-6+,Iba-1+ IL-1β +,GFAP+ TNF-α +,GFAP+ IL-6+,GFAP+ IL-1β + cells in hippocampal tissue were increased,SOD content was decreased in TBI group rats(P<0.05).Compared with TBI group,escape latency were decreased,the number of platform crossing and the time of platform stay were increased,the hippocampal neurons arrangement was regular,Nissl body was increased,TUNEL positive rate was decreased,Aβ,BACE-1,TNF-α,IL-6,IL-1β protein,MDAcontent,Iba-1+TNF-α+,Iba-1+IL-6+,Iba-1+IL-1β+,GFAP+TNF-α+,GFAP+ IL-6+,GFAP+ IL-1β+ cells in hippocampal tissue were decreased,SOD content was increased in Ad-BMSCs group and Ad-si-BACE-1-BMSCs group(P<0.05);And the effect of Ad-si-BACE-1-BMSCs on the above indicators in rats was better than that of Ad-BMSCs(P<0.05).Conclusions BMSCs modified with BACE-1 can inhibit oxidative stress and inflammatory response in TBI rats,and have a protective effect on the brain tissue of TBI rats.
Keywords：β-site amyloid precursor protein cleavage enzyme-1(BACE-1)Bone marrow mesenchymal stem cells(BMSCs)Traumatic brain injuryInflammationOxidative stress
Publication Date：2024-04-10
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：9( 314-322 )