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脐带间充质干细胞外泌体对脓毒症小鼠肝保护性研究

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目的 探讨脐带间充质干细胞产生的外泌体对脓毒症小鼠肝保护效果.方法 选择32只SPF级雄性Balc小鼠,6~8周龄,取8只作为control组(注射100 μL生理盐水),另24只小鼠造模,腹腔注射铜绿假单胞菌(P.aeruginosa),浓度1.5 × 109CFU/mL,100 μL,模型建立3 h后,随机分为模型组(model组,注射等体积生理盐水)、低浓度间充质干细胞外泌体治疗组(lc组,腹腔注射0.1 μg/μL hUCMSCs-exo,100 μL进行治疗)和高浓度间充质干细胞外泌体治疗组(hc组,腹腔注射0.5 μg/μL hUCMSCs-exo,100 μL进行治疗),每组8只.比较4组实验小鼠的肝组织病理损伤程度、肝脏功能水平、血液炎性因子水平和存活率.结果 病理组织切片显示,model组肝细胞排列不均,核破裂,出现溶解性坏死,大量空泡变性,炎性细胞浸润;lc组肝细胞排列不均,细胞核固缩,大量空泡,炎性细胞浸润;hc组小鼠的肝细胞形态恢复,数量增多,肝细胞排列相对整齐,水肿和空泡减轻.与model组相比,hc组小鼠肝脏丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)及胆红素(Bilirubin)水平显著降低,有统计学差异(P<0.01);hc组小鼠接受治疗24 h后,血清中IL-1β、IL-6、TNF-α水平显著降低,有统计学差异(P<0.05);对小鼠治疗后72 h平均存活率做log-rank检验,结果显示,lc组与hc组存活率均有不同程度提高.结论 脐带间充质干细胞外泌体对脓毒症小鼠的肝脏具有保护作用,有助于减少小鼠肝脏组织损伤,降低炎性因子水平,提高脓毒症小鼠存活率.
Liver protective effect of umbilical mesenchymal stem cell exosomes on mice with sepsis
Objective To investigate the protective effect of exosomes produced by umbilical cord mesen-chymal stem cells on acute liver injury caused by sepsis in mice.Methods 32 male SPF Bale mice aged 6~8 weeks were selected,8 mice were selected as the control group(injected with 100 μL of saline),and the other 24 mice were used as the model.Pseudomonas aeruginosa(P.aeruginosa)was intraperitoneally in-jected at a concentration of 1.5×109 CFU/mL,100 μL.Three hours after the model was established,the mice were randomly divided into model group(model group,injected with equal volume of normal saline),low concentration mesenchymal stem cell exosomes treatment group(lc group,intraperitoneally injected with 0.1 μg/μL hUCMSCs-exo,100 μL)and high concentration mesenchymal stem cell exosomes treat-ment group(hc group,intraperitoneally injected with 0.5 μg/µL hUCMSCs-exo,100 μL),with 8 mice in each group.The pathological injury degree of liver tissue,liver function level,blood inflammatory factor level and survival rate of four groups of experimental mice were compared.Results Pathological histologi-cal sections showed heterogeneous arrangement of hepatocytes,nuclear rupture,lysogenous necrosis,massive vacuolar degeneration and inflammatory cell infiltration in the model group.lc group showed het-erogeneous arrangement of hepatocytes,nuclear consolidation,massive vacuolation and inflammatory cell infiltration.hc group mice showed restoration of the morphology of the hepatocytes,an increase in the number of hepatocytes,and a reduction in the arrangement of hepatocytes in the relative neatness of the oedema and vacuoles.Compared with model group,the liver alanine aminotransferase(ALT),aspartate aminotransferase(AST)and bilirubin levels in the hc group mice were remarkably reduced,and the differ-ences were statistically significant(P<0.01).After 24 hours of treatment in the hc group,the IL-1β,IL-6,and TNF-α in serum levels were significantly reduced(P<0.05).A log-rank test was performed on the average survival rate after 72 hours of modeling.According to the results,the survival rate of both lc and he groups was extended to varying degrees.Conclusion Extracellular vesicles of umbilical cord mesenchy-mal stem cells have a protective effect on acute liver injury in mice caused by sepsis,which can help reduce liver tissue damage,lower levels of inflammatory factors,and improve liver function,thereby prolonging the survival time of mice and increasing survival rates.

umbilical cord mesenchymal stem cellsexosomessepsisliver injury

李琴、倪萍、张旭华、许彭、哈晓丹、迪拉热·力迪甫、李秀梅

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新疆医科大学基础医学院形态中心,乌鲁木齐 830017

新疆地方病分子生物学重点实验室,乌鲁木齐 830011

脐带间充质干细胞 外泌体 脓毒症 肝损伤

新疆维吾尔自治区自然科学基金青年项目

2021C01C276

2024

新疆医科大学学报
新疆医科大学

新疆医科大学学报

CSTPCD
影响因子:0.76
ISSN:1009-5551
年,卷(期):2024.47(7)