摘要
目的:探究牛奶外泌体(mEXO)减少泼尼松龙(PSL)治疗杜兴肌肉萎缩症(DMD)的药物不良反应的效果。方法:将超速离心法收集的mEXO与PSL共孵育得到生物纳米药物(mEXO_(PSL));通过高效液相色谱(HPLC)检测药物装载效率;对DMD模型mdx小鼠给予口服治疗;监测mdx小鼠体重和体长变化,评估mEXO减轻PSL引起的生长抑制不良反应的效果,利用苏木素-伊红(HE)染色和micro-CT分析骨体积分数(BV/TV)、骨小梁数目(Tb.N)、骨小梁厚度(Tb.Th)和骨小梁间隙(Tb.Sp)等骨密度相关指标,评估mEXO减轻PSL引起的骨质疏松不良反应的效果;利用HE染色和CD68免疫组织化学染色检测肌肉病理情况及炎症浸润情况,评估mEXO_(PSL)的治疗效果。结果:通过共孵育可实现54.6%PSL在mEXO的负载;mdx小鼠经治疗后,与PSL组相比,mEXO_(PSL)组mdx小鼠体重(P<0.01)及体长(P<0.01)显著增加;与PSL组相比,mEXO_(PSL)组mdx小鼠的BV/TV(P<0.01)、Tb.N(P<0.01)和Tb.Th(P<0.05)显著增加,Tb.Sp(P<0.05)显著减少;与生理盐水组相比,PSL组和mEXO_(PSL)组肌肉病理以及炎症浸润均显著改善。结论:mEXO_(PSL)显著减少了mdx小鼠的生长抑制及骨质疏松药物不良反应,对PSL进行了药物改良。
Objective:To explore the effect of milk exosomes(mEXO)on reducing the adverse drug reactions of prednisolone(PSL)in the treatment of Duchenne muscular dystrophy(DMD).Methods:PSL was co-incubated with mEXO collected by ultracentrifugation to obtain bionanomedicine(mEXO_(PSL)).Drug loading efficiency was detected by high-performance liquid chromatography(HPLC).DMD model mdx mouse was treated by oral administration.The changes in body weight and length of mdx mouse were monitored to evaluate the effect of mEXO on reducing growth inhibition adverse reactions caused by PSL.Bone density related indicators such as bone volume fraction(BV/TV),number of trabeculae(Tb.N),thickness of trabeculae(Tb.Th)and trabecular space(Tb.Sp)were detected by hematoxylin eosin(HE)staining and micro-CT to evaluate the effect of mEXO on reducing osteoporosis adverse reactions caused by PSL.Muscle pathology and inflammatory infiltration were detected by HE staining and CD68 immunohistochemical staining to evaluate the therapeutic effect of mEXO_(PSL).Results:54.6%PSL could be loaded on mEXO by co incubation.After treatment,the mdx mice in the mEXO_(PSL)group showed a significant increase in body weight(P<0.01)and length(P<0.01)compared to the PSL group.Compared with the PSL group,the BV/TV(P<0.01),Tb.N(P<0.01)and Tb.Th(P<0.05)of mdx mice in the mEXO_(PSL)group significantly increased,while Tb.Sp(P<0.05)significantly decreased.Compared with the saline group,both the PSL group and mEXO_(PSL)group showed significant improvements in muscle pathology and inflammatory infiltration.Conclusion:mEXO_(PSL)significantly reduces growth inhibition and osteoporosis adverse drug reactions in mdx mice,and improves the drug treatment of PSL in DMD.
作者
钟丽
宋军
栗瑞斌
韩刚
尹海芳
ZHONG Li;SONG Jun;LI Ruibin;HAN Gang;YIN Haifang(Department of Cell biology,School of Basic Medical Sciences,Tianjin Medical University,Tianjin 300070,China;Department of Clinical Biochemistry,School of Medical Technology,Tianjin Medical University,Tianjin 300203,China)
出处
《天津医科大学学报》
2024年第3期218-223,共6页
Journal of Tianjin Medical University
基金
天津市研究生科研创新项目(2022SKY218)。
