间充质干细胞外泌体调控氧化应激减轻D氨基半乳糖/脂多糖诱导的急性肝损伤

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Abstract Objective: To explore the therapeutic effect and possible mechanism of exosomes derived from mouse mesenchymal stem cells(MSC) on Dgalactosamine hydrochloride/lipopolysaccharides induced acute liver injury. Methods: Mouse mesenchymal stem cells were extracted and detected by flow cytometry and cell differentiation experiment. The exosomes of MSC were collected and purified by ultracentrifugation and identified by transmission electron microscopy and Western blotting. Size distribution and zeta potential of exosomes were measured by NTA. The ability of exosomes to reduce the oxidative damage was detected by reactive oxygen species(ROS) fluorescence probe. CCK-8 assay was used to investigate the protective effect of exosomes on hepatocytes. The therapeutic effect of exosomes on D-GalN/LPS-induced ALI was also evaluated. Results: Primary mesenchymal stem cells expressed CD29 and CD44 but did not express CD31 and CD117. The exosomes derived from mesenchymal stem cells were nano-sized vesicles with typical cup-shaped structure, which expressed CD9 and CD63. Compared with PBS group, exosomes could reduce the level of ROS and improve the viability of L02 cells, while exosomes themselves had no obvious effect on cell viability. Compared with PBS group, exosomes could reduce liver damage and transaminase level, regulate the levels of malondialdehyde, catalase and superoxide dismutase. Conclusion: At the cellular level, exosomes derived from mesenchymal stem cells could reduce ROS level and protect hepatocyte viability. At the animal level, exosomes could down regulate the expression of oxidative stressrelated markers and promote liver tissue repair.

Received: 02 May 2020

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http://zzs.ujs.edu.cn/xbyxb/EN/ OR http://zzs.ujs.edu.cn/xbyxb/EN/Y2020/V30/I04/287

［1］William B, Julia W. Acute liver failure\[J\]. N Engl J Med, 2013，369(26): 2525-2534.

［2］Teoh NC, Farrell GC. Hepatic ischemia reperfusion injury: pathogenic mechanisms and basis for hepatoprotection\[J\]. J Gastroenterol Hepatol, 2003，18(8): 891-902.

［3］Borrelli DA, Yankson K, Shukla N, et al. Extracellular vesicle therapeutics for liver disease\[J\]. J Control Release, 2018，273: 86-98.

［4］Liu X, Wang T, Liu X, et al. Biochanin A protects lipopolysaccharide/Dgalactosamineinduced acute liver injury in mice by activating the Nrf 2 pathway and inhibiting NLRP3 inflammasome activation\[J\]. Int Immunopharmacol, 2016，38: 324-331.

［5］Haga H, Yan IK, Takahashi K, et al. Extracellular vesicles from bone marrowderived mesenchymal stem cells improve survival from lethal hepatic failure in mice\[J\]. Stem Cells Transl Med, 2017，6(4): 1262-1272.

［6］Yang D, Yuan Q, Balakrishnan A, et al. MicroRNA125b5p mimic inhibits acute liver failure\[J\]. Nat Commun, 2016，7: 11916.

［7］Woolbright BL, Jaeschke H. Role of the inflammasome in acetaminopheninduced liver injury and acute liver failure\[J\]. J Hepatol, 2017，66(4): 836-848.

［8］Jin G, Qiu G, Wu D, et al. Allogeneic bone marrowderived mesenchymal stem cells attenuate hepatic ischemiareperfusion injury by suppressing oxidative stress and inhibiting apoptosis in rats\[J\]. Int J Mol Med, 2013，31(6): 1395-1401.

［9］Cheng K, Rai P, Plagov A, et al. Transplantation of bone marrowderived MSCs improves cisplatinuminduced renal injury through paracrine mechanisms\[J\]. Exp Mol Pathol, 2013，94(3): 466-473.

［10］Schrepfer S, Deuse T, Reichenspurner H, et al. Stem cell transplantation: the lung barrier\[J\]. Transplant Proc, 2007，39(2): 573-576.

［11］Eggenhofer E, Benseler V, Kroemer A, et al. Mesenchymal stem cells are shortlived and do not migrate beyond the lungs after intravenous infusion\[J\]. Front Immunol, 2012，3: 297.

［12］Veerman RE, Gülüler Akpinar G, Eldh M, et al. Immune cellderived extracellular vesiclesfunctions and therapeutic applications\[J\].Trends Mol Med, 2019， 25(5): 382-394.

［13］Gudbergsson JM, Jnsson K, Simonsen JB, et al. Systematic review of targeted extracellular vesicles for drug deliveryconsiderations on methodological and biological heterogeneity\[J\]. J Control Release, 2019，306: 108-120.

［14］Mathieu M, MartinJaular L, Lavieu G, et al. Specificities of secretion and uptake of exosomes and other extracellular vesicles for celltocell communication\[J\]. Nat Cell Biol, 2019，21(1): 9-17.

［15］Gangadaran P, Rajendran RL, Lee HW, et al. Extracellular vesicles from mesenchymal stem cells activates VEGF receptors and accelerates recovery of hindlimb ischemia\[J\]. J Control Release, 2017，264: 112-126.

［16］翟骁, 王一然, 朱明向，等.间充质干细胞来源外泌体在氧化应激损伤中的研究进展\[J\].第二军医大学学报,2018,39(7): 716-721.

［17］Jiang W, Tan Y, Cai M, et al. Human umbilical cord MSCderived exosomes suppress the development of CCl4induced liver injury through antioxidant effect\[J\]. Stem Cells Int, 2018，2018: 1-11.

［18］Yan Y, Jiang W, Tan Y, et al. hucMSC exosomederived GPX1 is required for the recovery of hepatic oxidant injury\[J\]. Mol Ther, 2017，25(2): 465-479.

［19］Wang K, Jiang Z, Webster KA, et al. Enhanced cardioprotection by human endometrium mesenchymal stem cells driven by exosomal MicroRNA21\[J\]. Stem Cells Transl Med, 2017，6(1): 209-222.

［20］Lin KC, Yip HK, Shao PL, et al. Combination of adiposederived mesenchymal stem cells(ADMSC) and ADMSCderived exosomes for protecting kidney from acute ischemiareperfusion injury\[J\]. Int J Cardiol, 2016，216: 173-185.