桃红四物汤对兔肩袖损伤的修复作用及机制  

Repair Effect and Mechanism of Taohong Siwu Decoction on Rotator Cuff Injury in Rabbits

作　　者：徐众华 许炯博 钱文武 阙云端 王秋平 陈建发[3] XU Zhonghua;XU Jiongbo;QIAN Wenwu;QUE Yunduan;WANG Qiuping;CHEN Jianfa(Dept.of Orthopaedics,Nanjing Gaochun People’s Hospital,Nanjing 211302,China;The First Clinical Medical College,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Dept.of Four Orthopedics,the First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China)

机构地区：[1]南京市高淳人民医院骨科,南京211302 [2]广州中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

出　　处：《中国药房》2021年第24期2975-2979,共5页China Pharmacy

基　　金：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)。

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+6.4μg/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。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 lowdose,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 LC3Ⅱwere 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 highdose 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 obviou

关 键 词：桃红四物汤 肩袖损伤 PI3K/Akt/mTOR信号通路 自噬 兔 

分 类 号：R285.5[医药卫生—中药学]