波棱甲素纳米混悬剂体内外抗乙肝病毒实验研究

Experimental Study on Herpetrione Nanosuspension Against Hepatitis B Virus in Vitro and in Vivo

目的研究波棱甲素纳米混悬剂(PEDX-NS)的体内外抗乙肝病毒活性。方法本实验选择Hep G2 2.2.15细胞系和鸭乙肝病毒感染模型两种模型评价波棱甲素纳米混悬剂的体内外抗乙肝病毒活性,并与波棱甲素普通混悬剂(PEDX-CS)进行比较。结果体外实验结果显示,波棱甲素纳米混悬剂可有效抑制2.2.15细胞抗原(HBs Ag和HBe Ag)的分泌,并呈现一定的剂量依赖性,且波棱甲素纳米混悬剂的抑制作用显著高于波棱甲素普通混悬剂(P<0.05或P<0.01)。体内实验结果显示,高、中剂量(100、60 mg·kg-1)波棱甲素纳米混悬剂可显著降低鸭血清乙肝病毒-DNA的水平(P<0.05或P<0.01),且效果优于同剂量的波棱甲素普通混悬剂(P<0.05或P<0.01)。结论结果表明,波棱甲素纳米混悬剂体内外均具有抗乙肝病毒活性,且抗病毒作用明显优于波棱甲素普通混悬剂,其机制可能在于将其制成纳米混悬剂之后,粒径减小,表面积增大,体内吸收增加,从而使它的药效作用增强。

OBJECTIVE To evaluate the anti-hepatitis B virus（ HBV） activity of herpetrione nanosuspension（ PEDX-NS） both in vitro and in vivo. METHODS Hep G2 2. 2. 15 cells and duck hepatitis B virus（ DHBV） infected ducks as in vitro and in vivo models were used to compare the anti-HBV activity of PEDX-NS and PEDX coarse suspension（ PEDX-CS）. RESULTS In the Hep G2 2. 2. 15 cell,PEDX-NS effectively suppressed the secretion of the HBV antigens（ HBs Ag and HBe Ag） in a dose-dependent manner with significant difference from PEDX-CS（ P〈0. 05 or P〈0. 01）. In the in vivo evaluation,PEDX-NS with high dose（ 100mg·kg- 1） and middle dose（ 60 mg·kg- 1） significantly reduced the serum HBV DNA level（ P〈0. 05 or P〈0. 01） and the effect was better than that of PEDX-CS（ P〈0. 05 or P〈0. 01）. CONCLUSION The result revealed that PEDX-NS exhibits anti-HBV activity both in vitro and in vivo and its effect was superior to that of PEDX-CS. The mechanism is probably that the small particle size of PEDX-NS provides a large specific surface area that resulted in better absorption in vivo,thus enhancing its anti-HBV activity.