Page 63 - 《中国药房》2021年第6期

补骨脂素对绝经后大鼠骨质疏松及PI3K/Akt/mTOR信号通路的

影响 Δ

1＊
陈露华 ，唐宏宇（1.广州中医药大学第一附属医院药房，广州 510405；2.广州中医药大学第一附属医院三骨
2
科，广州 510405）

中图分类号 R683；R285 文献标志码 A 文章编号 1001-0408（2021）06-0697-05
DOI 10.6039/j.issn.1001-0408.2021.06.09
摘 要 目的：研究补骨脂素对绝经后大鼠骨质疏松及磷脂酰肌醇 3 激酶（PI3K）/蛋白激酶 B（Akt）/哺乳动物雷帕霉素靶蛋白
（mTOR）信号通路的影响。方法：将60只健康雌性SD大鼠随机分为正常组、模型组、阳性对照组（0.09 mg/kg雌二醇）和补骨脂素
低、中、高剂量组（22、44、88 mg/kg），每组10只。除正常组外，其余各组大鼠均采用卵巢摘除去势法建立绝经后骨质疏松模型。术
后正常饲养2个月，正常组和模型组大鼠灌胃等体积生理盐水，各药物组大鼠灌胃相应药液；灌胃体积均为0.005 mL/g，每天1次，
连续98天。末次给药24 h后，测定大鼠右侧下肢股骨和椎骨的骨密度，血清中钙离子、骨钙素、Ⅰ型前胶原N端前肽（P1NP）含量
和骨形态发生蛋白2（BMP2）、血管内皮生长因子（VEGF）水平，以及股骨组织中PI3K、Akt、mTOR mRNA及蛋白的表达水平。结
果：与正常组比较，模型组大鼠股骨和椎骨的骨密度以及血清中钙离子、骨钙素、P1NP 含量和 BMP2、VEGF 水平均显著降低，
PI3K、Akt、mTOR mRNA及蛋白的表达水平均显著升高（P＜0.05或P＜0.01）。与模型组比较，补骨脂素中、高剂量组和阳性对照
组大鼠股骨和椎骨的骨密度以及血清中钙离子、骨钙素、P1NP含量和BMP2（补骨脂素中剂量组除外）、VEGF（补骨脂素中剂量组除
外）水平均显著升高，各药物组PI3K、Akt、mTOR mRNA（补骨脂素低剂量组除外）及蛋白表达水平均显著降低（P＜0.05或P＜0.01），
且高剂量组股骨骨密度和钙离子、BMP2水平以及PI3K蛋白表达水平均显著高于阳性对照组（P＜0.05），mTOR mRNA表达水平显著
低于阳性对照组（P＜0.05）。结论：补骨脂素可改善绝经后大鼠的骨质疏松，其机制可能与抑制PI3K/Akt/mTOR信号通路有关。
关键词 补骨脂素；绝经后骨质疏松症；磷脂酰肌醇3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白信号通路；大鼠

Effect of Psoralen on Osteoporosis in Postmenopausal Rats and PI3K/Akt/mTOR Signaling Pathway
2
1
CHEN Luhua ，TANG Hongyu（1. Dept. of Pharmacy，the First Affiliated Hospital of Guangzhou University of
TCM，Guangzhou 510405；2. Third Dept. of Orthopedics，the First Affiliated Hospital of Guangzhou University
of TCM，Guangzhou 510405，China）

ABSTRACT OBJECTIVE：To study the effect of psoralen on osteoporosis in postmenopausal rats and PI3K/Akt/mTOR signaling
pathway. METHODS：Totally 60 healthy female SD rats were randomly divided into normal group，model group，positive control
group（0.09 mg/kg estradiol），psoralen low-dose，medium-dose and high-dose groups（22，44，88 mg/kg），with 10 rats in each
group. Except for normal group，the other groups were ovariectomized to establish Postmenopausal osteoporosis model. After 2
months of normal feeding after operation，normal group and model group were given the constant volume of normal saline
intragastrically，and administration groups were given the corresponding solution intragastrically；the volume was 0.005 mL/g，
once a day，for consecutive 98 days. 24 h after last administration，the BMD of femur and vertebra of right lower extremities in
rats was determined. The contents of serum calcium，osteocalcin and P1NP，the serum levels of BMP2 and VEGF were
determined；mRNA and protein expression of PI3K，Akt and mTOR in femur tissue were detected.RESULTS：Compared with
normal group，BMD of femur and vertebra，serum contents of calcium，osteocalcin，P1NP and serum levels of BMP2，VEGF in
model group were decreased significantly，while the mRNA and protein expression of PI3K，Akt and mTOR were increased
significantly （P＜0.05 or P＜0.01）. Compared with model group，BMD of femur and vertebra，serum levels of calcium，
osteocalcin，P1NP and serum levels of BMP2（except for psoralen medium-dose group），VEGF（except for psoralen medium-dose
group） were increased significantly in psoralen medium-dose and high-dose groups，positive control group，while the mRNA
expression（except for psoralen low-dose group）and protein expression of PI3K，Akt and mTOR in administration groups were
decreased significantly（P＜0.05 or P＜0.01）；BMD of femur，serum levels of calcium，BMP2 and PI3K protein expression in
psoralen high-dose group were significantly higher than positive control group （P＜0.05），and mTOR mRNA expression in
psoralen high-dose group was significantly lower than positive control group（P＜0.05）. CONCLUSIONS：Psoralen can improve
osteoporosis in postmenopausal rats，the mechanism of which may be associated with inhibiting PI3K/Akt/mTOR signaling pathway.
KEYWORDS Psoralen；Postmenopausal osteoporosis；PI3K/
Δ 基金项目：国家自然科学基金资助项目（No.81774339）；广东省
Akt/mTOR signaling pathway；Rat
中医药管理局项目（No.20191099）
＊药师。研究方向：中药药理学。E-mail：952458566@qq.com

中国药房 2021年第32卷第6期 China Pharmacy 2021 Vol. 32 No. 6 ·697 ·