p38MAPK-siRNA脂质体递药系统的制备及体外抗炎作用的初步研究  

Preparation and in vitro anti-inflammatory effect study of p38MAPK-siRNA liposome drug delivery system

作　　者：王元芳 汪家鼎 吴青思 李林 张志荣[1] WANG Yuanfang;WANG Jiading;WU Qingsi;LI Lin;ZHANG Zhirong(Key Laboratory of Drug-Targeting and Drug Delivery Systems of Education Ministry,West China School of Pharmacy,Sichuan University,Chengdu,Sichuan,610041 P.R.China)

机构地区：[1]四川大学华西药学院靶向药物与释药系统教育部重点实验室,四川成都610041

出　　处：《华西药学杂志》2020年第2期131-134,共4页West China Journal of Pharmaceutical Sciences

基　　金：国家自然科学基金资助项目(批准号:81690261)。

摘　　要：目的制备一种递送p38MAPK-siRNA的阳离子脂质体,研究其对脂多糖(LPS)诱导的小鼠RAW264.7炎症细胞模型的抗炎作用。方法采用薄膜分散-超声法制备p38MAPK-siRNA阳离子脂质体;用超速离心法分离制剂和游离p38MAPK-siRNA,通过荧光标记法检测脂质体对p38MAPK-siRNA的包封率;选用小鼠RAW264.7单核巨噬细胞为细胞模型,考察制剂的体外抗炎作用。结果成功制备了阳离子脂质体,p38MAPK-siRNA与其的包封率为87.29%;制剂具有一定的体外抗炎作用,通过抑制p38MAPK信号通路的活化,降低相关炎症因子IL-6、TNF-α的表达水平,从而发挥细胞抗炎作用。结论以小分子干扰RNA作为治疗手段的新型递药系统在未来药物治疗领域具有巨大的潜力。OBJECTIVE To prepare a cation-liposome for p38 MAPK-siRNA delivery, and then to investigate anti-inflammatory effect of the preparation on LPS induced RAW264.7 inflammatory cell model.METHODS The cation p38 MAPK-siRNA liposome was prepared with lipid hydration-sonication method.Free siRNA and siRNA-liposome preparation were separated by ultracentrifugation.Encapsulation efficiency of the preparation was determined by fluorospectrophotomete.Mouse RAW264.7 macrophage cell was selected as a cell model,investigating the anti-inflammatory effect in vitro.RESULTS Cation p38 MAPK-siRNA liposome was successfully prepared with the encapsulation efficiency of 87.29%.The preparation could inhibit inflammation in vitro by inhibiting the activation of p38 MAPK signal pathway,down-regulating the expression of related inflammatory cytokines IL-6 and TNF-α,thus leading to cell inflammation.CONCLUSION siRNA drug delivery system has great potential in the future therapy.

关 键 词：p38MAPK-siRNA 阳离子脂质体 超高速离心法 探头超声 包封率 抗炎 RAW264.7巨噬细胞 

分 类 号：R94[医药卫生—药剂学] R96[医药卫生—药学]