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桃红四物汤对兔肩袖损伤的修复作用及机制                                                 Δ


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        徐众华 ，许炯博 ，钱文武 ，阙云端 ，王秋平 ，陈建发（1.南京市高淳人民医院骨科，南京 211302；2.广州中
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        医药大学第一临床医学院，广州 510405；3.广州中医药大学第一附属医院四骨科，广州 510405）
        中图分类号 R285.5         文献标志码 A           文章编号 1001-0408（2021）24-2975-05
        DOI  10.6039/j.issn.1001-0408.2021.24.06
        摘  要   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、11 g/kg）以及桃红四物汤+LY294002组[5.5 g/kg桃红四物汤+6.4 μg/kg LY294002（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。
        关键词 桃红四物汤；肩袖损伤；PI3K/Akt/mTOR信号通路；自噬；兔

        Repair Effect and Mechanism of Taohong Siwu Decoction on Rotator Cuff Injury in Rabbits
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        XU Zhonghua ，XU Jiongbo ，QIAN Wenwu ，QUE Yunduan ，WANG Qiuping ，CHEN Jianfa（1. Dept. of
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        Orthopaedics，Nanjing Gaochun People’s Hospital，Nanjing 211302，China；2. The First Clinical Medical
        College， Guangzhou University of Chinese Medicine， Guangzhou 510405， China； 3. Dept. of Four
        Orthopedics，the First Affiliated Hospital of Guangzhou University of Chinese Medicine，Guangzhou 510405，
        China）
        ABSTRACT   OBJECTIVE：To study the repair 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 + LY294002 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+LY294002 group was given Taohong siwu decoction intragastrically，and then injected
        with LY294002 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 PI3K，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 PI3K，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 Beclin1 and LC3Ⅱ
        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 observed in Taohong siwu decoction + LY294002
           Δ 基金项目：国家自然科学基金面上项目（No.81774339）；广东省
        中医药局科研课题（No.20191101）                              group；compared with model group，there was no significant
           ＊副主任医师。研究方向：骨科学。电话：025-57311232。E-              difference in above indexes of serum and tendon-bone interface
        mail：Xzhws936@163.com                              （P＞0.05）. CONCLUSIONS： Taohong siwu decoction may


        中国药房    2021年第32卷第24期                                            China Pharmacy 2021 Vol. 32 No. 24  ·2975 ·
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