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纸质出版日期:2021,
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徐众华, 许炯博, 钱文武, 等. 桃红四物汤对兔肩袖损伤的修复作用及机制[J]. 中国药房, 2021,32(24).
XU Zhonghua, XU Jiongbo, QIAN Wenwu, et al. Repair Effect and Mechanism of Taohong Siwu Decoction on Rotator Cuff Injury in Rabbits[J]. China Pharmacy, 2021,32(24).
目的:研究桃红四物汤对兔肩袖损伤的修复作用及机制。方法:将新西兰兔随机分为空白对照组、模型组和桃红四物汤低、中、高剂量组(2.75、5.5、11g/kg)以及桃红四物汤+LY294002组[5.5g/kg桃红四物汤+6.4μg/kgLY294002(通路抑制剂)],每组11只。除空白对照组外,其余各组兔均行右侧肩胛下肌部分离断手术,复制肩袖损伤模型。造模成功后,空白对照组和模型组兔均灌胃生理盐水,桃红四物汤各剂量组兔均灌胃相应药液,桃红四物汤+LY294002组兔先灌胃桃红四物汤药液,再耳缘注射LY294002,每天1次,连续12周。末次灌胃(注射)后,观察兔腱骨界面组织的病理形态学变化,检测兔血清中肿瘤坏死因子α(TNF-α)、白细胞介素10(IL-10)、IL-6水平,检测兔腱骨界面组织中磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(Akt)、哺乳动物雷帕霉素靶蛋白(mTOR)的mRNA和蛋白表达水平以及自噬相关蛋白(Beclin1、LC3Ⅱ)的表达水平。结果:与空白对照组比较,模型组兔腱骨界面组织凹凸不平,内膜肿胀;血清中TNF-α、IL-6水平以及腱骨界面组织中PI3K、Akt、mTOR的mRNA和蛋白表达水平均显著升高(P<0.05或P<0.01),IL-10水平以及Beclin1、LC3Ⅱ蛋白的表达水平均显著降低(P<0.01)。与模型组比较,桃红四物汤低、中剂量组兔腱骨界面组织仍存在一定的内膜破损,高剂量组兔腱骨界面组织光滑平整、内膜无明显撕裂;各剂量组兔血清和腱骨界面组织中大部分指标水平均显著逆转(P<0.05或P<0.01)。桃红四物汤+LY294002组兔腱骨界面组织仍肿胀膨大,内膜撕裂明显;血清和腱骨界面组织中上述指标水平较模型组差异均无统计学意义(P>0.05)。结论:桃红四物汤可修复兔的肩袖损伤,其作用机制与抑制PI3K/Akt/mTOR信号通路、激活自噬、抑制炎症反应有关。
OBJECTIVE:To study the repa ir effect and mechanism of Taohong siwu decoction on rotator cuff injury in rabbits. METHODS:New Zealand rabbits were randomly divided into blank control group ,model group ,Taohong siwu decoction low-dose,medium-dose and high-dose groups (2.75,5.5,11 g/kg),and Taohong siwu decoction+LY 294002 group [ 5.5 g/kg Taohong siwu decoction+ 6.4 μg/kg LY294002(pathway inhibitor )],with 11 rabbits in each group. Except for blank control group , other groups underwent right subscapularis muscle detachment to establish rotator cuff injury model. After modeling ,blank control group and model group were given normal saline intragastrically ;Taohong siwu decoction groups were given relevant medicine intragastrically;Taohong siwu decoction+LY 294002 group was given Taohong siwu decoction intragastrically ,and then injected with LY 294002 at the ear edge ,once a day ,for 12 weeks. After last intragastric administration (injection),the pathological changes of tendon-bone interface was observed ;the levels of TNF-α,IL-10 and IL- 6 in serum were detected ;mRNA and protein expressions of PI 3K,Akt and mTOR in tendon-bone interface were detected ;the expression of autophagy related protein (Beclin1, LC3Ⅱ)were detected. RESULTS :Compared with blank control group ,the tendon-bone interface was uneven and the intima was swollen in model group. Serum levels of TNF-α and IL-6,mRNA and protein expressions of PI 3K,Akt and mTOR in tendon-bone interface were increased significantly (P<0.05 or P<0.01),while the level of IL- 10 and protein expression of Beclin 1 and LC 3Ⅱ were decreased significantly (P<0.01). Compared with model group ,the tendon-bone interface of rabbits in Taohong siwu decoction low-dose and medium-dose groups still had certain intimal damage ,while the tendon-bone interface of rabbits in high-dose group was smooth and flat without an obvious intimal tear ;the levels of most indexes in serum and tendon-bone interface of rabbits were significantly reversed in each dose group (P<0.05 or P<0.01). Swollen tendon-bone interface and obvious intimal tear were obse rved in Taohong siwu decoction + LY group;compared with model group ,there w as no significant difference in above indexes of serum and tendon-bone interface (P>0.05). CONCLUSIONS :Taohong siwu decoction may repair the rotator cuff injury of rabbits ,the mechanism of which may be associated with inhibiting PI3K/Akt/mTOR signaling pathway,activating autophagy and inhibiting inflammatory response.
桃红四物汤肩袖损伤PI3K/Akt/mTOR信号通路自噬兔
Taohong siwu decoctionRotator cuff injuryPI3K/Akt/mTOR signaling pathwayAutophagyRabbit
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