牙髓间充质干细胞治疗自身免疫性肝炎小鼠模型的效果及其免疫调控机制

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Abstract：ObjectiveToinvestigate the therapeuticefectofdentalpulpstemcells（DPSCs）onautoimmunehepatisininvivo andinvitro experimentsandtherelated mechanism.MethodsAninvitroco-culturesystemwasusedtoevaluate the immunoregulatory efectof DPSCs，and32 mice wererandomlydividedinto healthycontrol group，modelgroup，positivedrug group，and DPSCs treatment group，with8 mice ineach group.The serum levelsof alanine aminotransferase（ALT），aspartate aminotransferase（AST），andinflammatoryfactors weremeasured，andHEstainingwasused toassessliverpathologicalinjuryAn analysisofvariance wasusedforcomparisonof normalldistributed continuous data between multiplegroups，and the least significant difference t -test was used for further comparison between two groups.ResultsThe in vitro experiment showed that the positive rates of CD105，CD73，and CD90in DPSCswere 99.97% ， 100% ，and 99.53% ，respectively，while the positive ratesof CD34，HLA-DR，and CD45were 0.56% ， 0.17% ，and O，respectively.DPSCs significantly inhibited the proliferation of Th1 and Th17 subsets，with inhibition rates of 31.32% and 45.76% ，respectively；DPSCs promoted the proliferation of Treg （CD4+CD25FoxP3+）， with a promoting rate of 52.29% . DPSCs had an inhibition rate of 93.70% on the proliferation of lymphocytes.In the mouse model of autoimmunehepatitis，comparedwiththe modelgroup，theDPSCs treatment grouphadsignificantreductions intheserumlevelsof ALTand AST，with reduction rates of 66.8% and 60.0% ，respectively（ t=3.321 and 2.907， P =0.0075andO.0175）andsignificant reductions in the inflammatory factors tumor necrosis factor- α and interleukin- 1β ，with reduction ratesof 57.5% and 71.3% ， respectively （t=2.484 and 2.796， P =0.039 8 and O.O20 6），and histopathological examination showed no significant improvement in periportal bridging necrosis （ t=1.969 ， P =0.098）.ConclusionDPSCs effectively alleviate immune-mediated liver injury through immunoregulation，which provides an experimental basis forclinical translation.

Key words：Mesenchymal Stem Cels；Dental Pulp;Hepatitis，Autoimmune；Mice，InbredBALBC；Immunoregulation

Research funding：Beijing Nova Program（20220484166）

自身免疫性肝炎（autoimmunehepatitis，AIH）是一种由自身免疫异常导致的肝脏炎症性疾病，多发于女性，其临床表现通常为转氨酶升高、自身抗体如抗核抗体及平滑肌抗体等检测阳性、IgG水平升高，病理方面表现为巨噬细胞和浆细胞增多，肝组织中淋巴细胞浸润形成界面性肝炎[1]。（剩余12652字）