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天津医科大学总医院药剂科,天津 300052
主管药师,硕士。研究方向:药理学。E-mail:hanbintj@163.com
主任药师。研究方向:药理学。E-mail:lee41@sina.com
收稿日期:2022-12-22,
修回日期:2023-07-03,
录用日期:2023-07-05,
纸质出版日期:2023-07-30
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韩滨,郝晨伟,董敏,等.桃红四物汤改善紫杉醇导致的大鼠外周神经损伤的机制研究[J].中国药房,2023,34(14):1707-1711.
HAN Bin,HAO Chenwei,DONG Min,et al.Study on the mechanism of Taohong siwu decoction improving peripheral nerve injury induced by paclitaxel in rats[J].ZHONGGUO YAOFANG,2023,34(14):1707-1711.
韩滨,郝晨伟,董敏,等.桃红四物汤改善紫杉醇导致的大鼠外周神经损伤的机制研究[J].中国药房,2023,34(14):1707-1711. DOI: 10.6039/j.issn.1001-0408.2023.14.09.
HAN Bin,HAO Chenwei,DONG Min,et al.Study on the mechanism of Taohong siwu decoction improving peripheral nerve injury induced by paclitaxel in rats[J].ZHONGGUO YAOFANG,2023,34(14):1707-1711. DOI: 10.6039/j.issn.1001-0408.2023.14.09.
目的
2
探索桃红四物汤(THD)改善紫杉醇(PTX)导致的大鼠外周神经损伤的作用机制。
方法
2
考察THD(1 g/mL含药血清)、PTX(0.1 μmol/L)单用和联用下对施万细胞系RSC96细胞增殖率以及自噬溶酶体关联膜蛋白2(LAMP2)、自噬标记蛋白酵母Atg6同源物(Beclin1)、磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(Akt)、哺乳动物雷帕霉素靶蛋白(mTOR)表达的影响,并与自噬促进剂雷帕霉素和自噬抑制剂3-甲基腺嘌呤(3-MA)进行比较。考察THD高、低剂量对PTX导致的外周神经损伤模型大鼠坐骨神经中髓鞘碱性蛋白质(MBP)、鞘磷脂蛋白(MPZ)、S100钙结合蛋白(S100)、LAMP2、Beclin1、PI3K、Akt、mTOR表达的影响。
结果
2
THD+PTX作用下RSC96细胞增殖率显著高于PTX单用;THD+PTX、THD+3-MA作用下RSC96细胞中LAMP2、Beclin1蛋白的表达显著高于PTX、3-MA单用,PI3K、Akt、mTOR蛋白的表达显著低于PTX、3-MA单用(
P
<0.05)。与模型组相比,THD高、低剂量组大鼠坐骨神经中MBP、MPZ、S100、LAMP2、Beclin1蛋白表达均显著升高,PI3K、Akt、mTOR蛋白表达均显著降低(
P
<0.05)。
结论
2
THD可能通过抑制PI3K/Akt/mTOR信号通路来激活施万细胞自噬,从而改善PTX导致的外周神经损伤。
OBJECTIVE
2
To explore the mechanism of Taohong siwu decoction (THD) improving peripheral nerve injury induced by paclitaxel (PTX) in rats.
METHODS
2
The effects of THD (1 g/mL drug-containing serum) and PTX (0.1 μmol/L) alone or in combination on the proliferation rate of Schwann cells line RSC96 as well as the expressions of lysosomal-associated membrane protein-2 (LAMP2), autophagy marker protein yeast Atg 6 homolog (Beclin1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR) were investigated, and then compared with autophagy promoter rapamycin and autophagy inhibitor 3-methyladenine (3-MA). The effects of high-dose and low-dose THD on the expressions of myelin basic protein (MBP) and myelin protein zero (MPZ), S100 calcium-binding protein (S100), LAMP2, Beclin1, PI3K, Akt and mTOR were tested at the end of the experiment.
RESULTS
2
After treatment of THD+PTX, the proliferation rate of RSC96 cells was significantly higher than those treated with PTX alone. After treatment of THD+PTX or THD+3-MA, the protein expressions of LAMP2 and Beclin1 in RSC96 cells were significantly higher than those treated with PTX or 3-MA alone, while the protein expressions of PI3K, Akt and mTOR were significantly lower than those treated with PTX or 3-MA alone (
P
<0.05). Compared with model group, the protein expressions of MBP, MPZ, S100, LAMP2 and Beclin1 in sciatic nerve of rats were increased significantly in THD high-dose and low-dose groups, while the protein expressions of PI3K, Akt and mTOR were significantly decreased (
P
<0.05).
CONCLUSIONS
2
THD may activate Schwann cell autophagy by inhibiting the PI3K/Akt/mTOR signaling pathway, thereby improving peripheral nerve injury caused by PTX.
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