Objective To discuss the effect of exosomes derived from human umbilical cord blood mesenchymal stem cells (Hu-MSCs) on movement ability of the intrauterine infection offspring rats and its mechanism, so as to provide new ideas for treating intrauterine infection and motor function impariment. Methods Ninety pregnant rats were randomly divided into three groups [the experimental group, the lipopolysaccharide(LPS) group and the control group].On the 15th day of embryo(E15), dams of the experimental group were given 0.5 ml 1×106 ng/μl intraperitoneal injection of exosomes, dams of the LPS group and the control group were given intraperitoneal injection of the same amount of physiological saline solution. On the 17th day of embryo(E17), dams of the experimental group and the LPS group were given intrauterine injection of 100 μl 25 μg/μl lipopolysaccharide (LPS) solution, and dams of the control group were given intrauterine injection of the same amount of normal saline. On the 18th day of embryo(E18), fifteen pregnant rats were randomly selected from the three groups and killed. Then ELISA method was used to check the change in the IL-4, IL-10 and IL-12 of the amniotic fluid of the pregnant rats and serum of the offspring. The remaining 15 pregnant rats in each group gave birth naturally and their pregnancy outcomes were observed. And 10 offspring were selected randomly to evaluate their movement ability by using Suspension Test and Basso-Beatie-Bresnahan Scale (BBB Scale) once 15 days old and once 30 days old. Results 1) The levels of IL-4 and IL-10 in the amniotic fluid of the dams and serum of the offspring in the experimental group were significantly elevated from those in the LPS group (t=8.26, 3.97, 7.66, 4.81, P<0.05). The levels of IL-12 in the amniotic fluid of the dams and serum of the offspring in the experimental group were significantly reduced from those of the LPS group (t=3.14, 6.68, P<0.05). 2) In suspension test, the grasp time of the 15-day-old and 30-day-old offspring in the LPS group was significantly shorter than those of the control group(t=8.166,16.283, P<0.05), which were also significantly shorter than those of the experimental group (t=4.867, 6.994, P<0.05).The BBB score of the 15-day-old and 30-day-old offspring in the LPS group were significantly lower than those of the control group (t＝7.394, 16.283, P<0.05),which were also significantly lower than those of the experimental group (t=4.096, 7.004, P<0.05). Conclusion The exosomes derived from human umbilical cord blood mesenchymal stem cells (Hu-MSCs) may improve the impairment of premature offspring pup's motor function by reducing the inflammatory response in pregnant and offspring rats.
Key words
exosomes /
mesenchymal stem cells /
intrauterine infection /
movement ability /
inflammatory factors
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References
[1] Zhang S,Teo KYW,Chuah SJ,et al.MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis[J].Biomaterials,2019, 200:35-47.
[2] 黄谱,宗璐.人脐血间充质干细胞来源的外泌体对早产子代大鼠学习记忆能力及海马的影响[J].西安交通大学学报:医学版,2020,41(3):317-321,332.
[3] 宗璐,吕晔,张小雪,等.宫内注射内毒素对早产子代大鼠学习记忆能力影响的研究[J].中国儿童保健杂志,2019,27(5):503-506.
[4] 贾清政,李晓捷.不同强度运动干预对宫内感染致脑损伤仔鼠运动功能的影响[J].中华临床医师杂志(电子版),2015,9(9):1613-1616.
[5] 郭岚敏,李晓捷,庞伟.宫内感染致脑瘫大鼠运动功能不同评定方法的比较[J].中国康复理论与实践,2010,16(3):224-227.
[6] Zhu LP, Tian T,Wang JY,et al. Hypoxia-elicited mesenchymal stem cell-derived exosomes facilitates cardiac repair through miR-125b-mediated prevention of cell death in myocardial infarction[J]. Theranostics, 2018, 8:6163-6177.
[7] Dong LY,Wang Y, Zheng TT,et al.Hypoxic hUCMSC-derived extracellular vesicles attenuate allergic airway inflammation and airway remodeling in chronic asthma mice[J]. Stem Cell Res Ther, 2021,12:4.
[8] Xu HY,Jia ZL,Ma K,et al.Protective effect of mesenchymal stromal cell derived exosomes on traumatic brain injury via miR-216a-5p[J]. Med Sci Monit, 2020, 26:e920855.
[9] Li MY, Li SS, Du CY,et al,Exosomes from different cells:Characteristics, modifications, and therapeutic applications[J]. Eur J Med Chem,2020, 207:112784.
[10] Pu XY,Ma SY, Gao Y,et al.Mesenchymal stem cell-derived exosomes:Biological function and their therapeutic potential in radiation damage[J].Cells, 2021, 10:42.
[11] Daan RMGO,Ruth G,Luise K,et al.Preterm brain injury, antenatal triggers, and therapeutics:Timing is key[J].Cells, 2020, 9(8):1871.
[12] Shen Y, Sun Y,Gu W, et al. Intrauterine infection affects early growth and neurobehavioral development in neonatal rats[J]. J Zhejiang Univ,2019, 48:58-64.
[13] 沈盈,孙逸,顾伟忠,等.宫内感染对新生大鼠早期生长及神经行为发育的影响[J].浙江大学学报:医学版,2019,48(1):58-64.
[14] Apodaca LA, Anoud DB, Garcia C, et al. Human neural stem cell-derived extracellular vesicles mitigate hallmarks of Alzheimer's disease[J]. Alzheimer's Res Ther, 2021, 13(1):1-18.
[15] Hyun JP,Jin YS,Ha NK,et al.Mesenchymal stem cells stabilize the blood-brain barrier through regulation of astrocytes[J]. Curr Stem Cell Res Ther,2015,6:187.
[16] 周燕,王琳,裴双,等.骨髓间充质干细胞外泌体可减少脊髓损伤后A1型星形胶质细胞的活化[J].中国组织工程研究,2019,23(21):3294-3301.
[17] 张丽,周锡昌,李冬梅.宫内感染早产儿血清及脑脊液炎性因子与脑损伤的关系[J].贵州医药,2020,44(5):720-721.
[18] Ni HQ, Yang S, Siaw-Debrah F,et al.Exosomes derived from bone mesenchymal stem cells ameliorate early inflammatory responses following traumatic brain injury[J]. Front Hum Neurosci, 2019,13:14.
[19] 雷舒尧,郏丽娜,徐磊,等.脐带血白介素-6和白介素-10水平在早产儿脓毒血症中的应用研究[J].中国现代医生,2020,58(3):54-56,59.
[20] Saraiva M, O'garra A. The regulation of IL-10 production by immune cells[J]. Nat Rev Immunol, 2010, 10:170-181.
[21] Cai GF,Cai GL, Zhou HC, et al. Mesenchymal stem cell-derived exosome miR-542-3p suppresses inflammation and prevents cerebral infarction[J].Stem Cell Res Ther, 2021, 12:1-12.
[22] Kim M, Shin DI, Choi BH, et al. Exosomes from IL-1β-primed mesenchymal stem cells inhibited IL-1β-and TNF-α-mediated inflammatory responses in osteoarthritic SW982 cells[J]. Tissue Eng Regen Med, 2021,18(4):1-12.
[23] Harrell CR, Volarevic A, Djonov V, et al. Mesenchymal stem cell-derived exosomes as new remedy for the treatment of neurocognitive disorders[J]. Int J Mol Sci, 2021, 22:1433.
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