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熊绍权, 邹晓玲, 郑巧等. 参附注射液对紫杉醇外周神经毒性的影响[J]. 四川大学学报(医学版), 2018, 49(1): 44-47.
引用本文: 熊绍权, 邹晓玲, 郑巧等. 参附注射液对紫杉醇外周神经毒性的影响[J]. 四川大学学报(医学版), 2018, 49(1): 44-47.
XIONG Shao-quan, ZOU Xiao-ling, ZHENG Qiao. et al. Effects of ShenFu Injection on Peripheral Neurotoxicity of Paclitaxel[J]. Journal of Sichuan University (Medical Sciences), 2018, 49(1): 44-47.
Citation: XIONG Shao-quan, ZOU Xiao-ling, ZHENG Qiao. et al. Effects of ShenFu Injection on Peripheral Neurotoxicity of Paclitaxel[J]. Journal of Sichuan University (Medical Sciences), 2018, 49(1): 44-47.

参附注射液对紫杉醇外周神经毒性的影响

Effects of ShenFu Injection on Peripheral Neurotoxicity of Paclitaxel

  • 摘要: 目的 研究参附注射液减轻紫杉醇外周神经毒性的作用,探讨其可能的作用机制。 方法 28只成年雄性Wister大鼠均分为4组(n=7):空白对照组、紫杉醇组、紫杉醇+参附低剂量组、紫杉醇+参附高剂量组。除空白对照组外,各组大鼠腹腔注射紫杉醇8 mg/kg,每4日一次,共注射4次。于实验第1天起,紫杉醇+参附低、高剂量组每日腹腔注射参附注射液(4 mL/kg、8 mL/kg),共21 d;空白对照组于实验第1天起,每日予等容量生理盐水腹腔注射,共21 d。分别于紫杉醇首次注射前(0 d),首次注射后6 d、14 d测定机械缩足反射阈值(MWT)和热缩足潜伏期(TWL);于第22天测定血清中神经生长因子(NGF)值后处死大鼠,用透射电镜观察坐骨神经超微结构。结果 紫杉醇组14 d时,大鼠MWT和TWL值较0 d时及同期空白对照组升高(P<0.05);与同期紫杉醇组相比,参附低、高剂量组MWT和TWL值下降,且与参附高剂量组的差异有统计学意义(P<0.05);与同期空白对照组相比,参附低、高剂量组MWT和TWL值均无明显升高(P>0.05)。与空白对照组相比较,紫杉醇组NGF值下降明显(P<0.05),参附低、高剂量组NGF值均较紫杉醇组升高,高剂量组升高明显(P<0.05)。与空白对照组比较,紫杉醇组大鼠坐骨神经纤维结构普遍破坏,髓鞘肿胀、碎裂、空泡化,雪旺氏细胞中内质网肿胀,基质结构紊乱,参附低剂量组破坏程度较紫杉醇组轻,参附高剂量组神经纤维结构较完整。结论 参附注射液具有减轻紫杉醇外周神经毒性的作用,其机制可能与促进血清中NGF的表达有关。

     

    Abstract: Objective To investigate the effects and the underlying mechanisms of ShenFu Injection on paclitaxel-induced peripheral neuropathy. Methods Twenty-eight adult male Wister rats were randomized into 4 groups (n=7): control group,paclitaxel group,paclitaxel combined with low or high dose of ShenFu Injection groups. Rats were intraperitoneally injected with paclitaxel 8 mg/kg every 4 d for a total of 4 doses except control group. From Day 1 of the experiment (injection), low dose (4 mL/kg) and high dose (8 mL/kg) of Shenfu Injection were intraperitoneally injected daily in the combination groups for a total of 21 d respectively, while normal saline (NS) was injected in control group in the same way instead. Mechanical withdraw threshold (MWT) and thermal withdraw latency (TWL) of rats’ hind paw were measured before (0 d) and after the first injection (6 d, 14 d). The level of nerve growth factor (NGF) in the serum was measured at 22 d before the euthanasia, and the ultrastructure of the sciatic nerve was observed with transmission electron microscope. Results The MWT and TWL of 14 d in paclitaxel group significantly increased compared with those of 0 d and control group (P<0.05). The combination of paclitaxel with ShenFu Injection, especially the high dose (P<0.05), significantly reduced the MWT and TWL when compared to paclitaxel group at 14 d. Compared with simultaneous control group, there was no remarkably increased MWT and TWL in the low and high dose of ShenFu Injection (P>0.05). Compared with control group, the serum NGF level significantly decreased (P<0.05) in paclitaxel group, while the serum NGF level in low and high dose of ShenFu Injection groups were higher than paclitaxel group, particularly in the high dose group (P<0.05). When compared to control group, the sciatic nerve fiber structure in the paclitaxel group was generally damaged, including myelin sheath swelling, fragmentation and vacuolization, endoplasmic reticulum swelling and matrix structure disorder in Schwann cells. The structural damages were mitigated in the low dose and high dose groups, especially the latter one, when compared to the paclitaxel group. Conclusion Shenfu Injection can reduce the peripheral neurotoxicity of paclitaxel by promoting the expression of NGF in serum.

     

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