Therapeutic effect of transplantation of ApoJ-modified bone marrow mesenchymal stem cells on intracere-bral hemorrhage in rats and its action mechanism / 医学研究生学报

ABSTRACT

Objective The nerve-protective effect of Apoli-poprotein J ( ApoJ) in intracerebral hemorrhage ( ICH) is not yet clarified.This study aimed to explore the therapeutic effect of trans -plantation of bone marrow mesenchymal stem cells (BMSCs) carrying the ApoJ gene on intracerebral hemorrhage in rats and its possible ac -tion mechanism. Methods Rat BMSCs were isolated, cultured in vitro, and transfected with the recombinant plasmid pEGFP -N1-ApoJ mediated with lipofectamine.Ninety-six SD rats were randomly divided into groups A, B and C, and ICH models were established by two -step autologous intracranial blood injection .At 24 hours after model-ing, the rats in groups A, B, and C were transplanted with the same volume of ApoJ-transfected BMSC suspension, BMSC suspension and normal saline, respectively.At 1, 3, 5 and 7 days after transplantation, the neurofunction recovery of the rats were evaluated with modified Neurological Severity Scores (mNSS), the brain water content measured by the dry -wet weight method, and the expression level of complement component 3 (C3) in the brain tissue detected by Western blot . Results The mNSS exhibited no statistically significant differences among the three group of rats on the 1st day after transplantation (P>0.05), but was remarkably lower in group A than in B and C on the 3rd (8.13±0.99 vs 9.25±1.28 and 10.88±0.84, P<0.05), 5th (6.75±1.04 vs 8.50±1.41 and 9.75±0.89, P<0.05) and 7th day (5.63±0.52 vs 7.00±0.54 and 7.88±1.25, P<0.05), and markedly lower in group B than in C (P<0.05).The water content in the brain tissue was also significantly lower in group A than in B and C on the 1st (78.17±0.82 vs 78.83±0.56 and 80.38±0.35, P<0.05), 3rd (78.68±0.55 vs 79.12±0.26 and 81.47±0.26, P<0.05), 5th (77.00±0.58 vs 78.13±0.46 and 79.74± 0.41, P<0.05) and 7th day (75.89±0.46 vs 76.86±0.29 and 78.44±0.44, P<0.05), and remarkably lower in group B than in C (P<0.05).Western blot showed that the expression of the C 3 protein in the brain tissue was markedly decreased in group A as compared with B and C on the 1st (0.096±0.011 vs 0.212±0.014 and 0.440±0.006, P<0.05), 3rd (0.083±0.005 vs 0.164±0.013 and 0.604± 0.011, P<0.05), 5th (0.064±0.009 vs 0.105±0.010 and 0.333±0.010, P<0.05), 7th day (0.045±0.007 vs 0.091±0.004 and 0.141± 0.003, P<0.05), and significantly lower in group B than in C (P<0.05). Conclusion ApoJ can promote the recovery of the neuro-logical function of ICH rats by inhibiting complement activation -mediated secondary brain damage and alleviating cerebral edema .