经皮椎间孔注射多柔比星与多柔比星脂质体对大鼠后肢行为学影响的比较

Comparison of the effect of percutaneous intervertebral foramen injection of doxorubicin or pegylated liposome doxorubicin on hind limb behavior in rats

目的:比较经皮椎间孔注射多柔比星与多柔比星脂质体(pegylated liposome doxorubicin,PLD)对成年大鼠后肢行为学的影响,探讨多柔比星脂质体对背根神经节(dorsal root ganglion,DRG)的镇痛作用。方法:健康雄性SD大鼠52只采用随机数字表法分为4组(n=13):生理盐水组(Vehicle组)、隐形脂质体组(Liposome组)、0.2%多柔比星组(DOX组)及0.2%多柔比星脂质体组(PLD组)。各组均采用经皮椎间孔注射方法,于大鼠左侧L4~5、L5~6椎间孔分别注射生理盐水、隐形脂质体注射液、0.2%多柔比星及0.2%多柔比星脂质体10μl。分别于注药前及注药后1天、3天、5天、7天、14天、21天、28天测定大鼠机械刺激缩足反射阈值(mechanical withdrawal threshold,MWT)和热缩足反射潜伏期(thermal withdrawal latency,TWL),并观察注药后大鼠后肢的运动情况。注药后3天,DOX组和PLD组随机各抽取3只大鼠,观察多柔比星自发荧光情况。结果:荧光显微镜显示,DOX组和PLD组大鼠注药侧DRG内均可见大量红色多柔比星自发荧光分布。与Vehicle组和Liposome组相比,DOX组注药后1周内、PLD组注药后2周内MWT值下降,与基础值比较差异无统计学意义;之后呈逐渐上升趋势,至注药后28天增高最明显(P<0.05);DOX组和PLD组注药后1天TWL值下降,与基础值比较差异有统计学意义(P<0.05),余各时点组内及组间比较差异均无统计学意义。注药后28天,DOX组轻微跛行率为30%,其余各组大鼠后肢运动功能均正常。结论:经皮椎间孔注射0.2%多柔比星脂质体对大鼠背根神经节能够产生和多柔比星相似的镇痛作用,且不影响下肢运动功能。

Objective:To compare the effects of percutaneous intervertebral foramen injection of doxorubicin or pegylated liposomes doxorubicin(PLD)on the behavior of hind limbs in adult rats,and to explore the analgesic effect of doxorubicin liposomes on dorsal root ganglion(DRG).Methods:Fifty-two healthy male SD rats were randomly divided into 4 groups(n=13):normal saline group(Vehicle group),stealth liposome group(Liposome group),0.2%doxorubicin group(DOX group)and 0.2%pegylated lipo-somes doxorubicin group(PLD group).According to the different groups,normal saline,stealth liposome,doxorubicin and pegylated liposomes doxorubicin 10μl were injected respectively into the intervertebral foramen of the left L4-5 and L5-6 of rats by percutaneous intervertebral foramen injection.Three days after administration,3 rats in DOX group and PLD group respectively were randomly selected to observe the spontaneous fluorescence of doxorubicin.The paw mechanical withdrawal threshold(MWT)and paw thermal withdrawal latency(TWL)of rats were measured before and after administration at 1,3,5,7,14,21 and 28 days,and the movement of hind limbs of rats after administration was also observed.Results:Fluorescence microscope showed that a large number of red doxorubicin autofluorescence distribution could be seen in the DRG on the injection side of DOX group and PLD group.Compared with Vehicle group and Liposome group,MWT value in DOX group decreased within 1 week after administration,while that within 2 weeks in PLD group after administration,and there were no significant differences compared with the basic value;then,the MWT showed a gradual upward trend,and the increase was most obvious at 28 days after administration(P<0.05);TWL value of DOX group and PLD group decreased at the first day after administration,and the difference was statistically significant compared with the basic value(P<0.05),and there was no statistically significant difference between the other time points.On the 28th day after injection,the slight claudication rate in DOX group was 30%,and the motor function of hind limbs in other groups was normal after administration.Conclusion:Percutaneous injection of pegylated liposomes doxorubicin into intervertebral foramen of rats can produce similar analgesia effect as doxorubicin,and does not affect the motor function of hind limbs.