三七总皂苷通过调控Wnt/β-catenin通路减轻家兔股骨头坏死  

Protective Effect of Panax Notoginseng Saponins on Femoral Head Necrosis in Rabbits by Regulating Wnt/β-Catenin Pathway

作　　者：陈杰[1] 张堃[2] 孔令俊[1] 王玉泉[1] Chen Jie;Zhang Kui;Kong Lingjun;Wang Yuquan(Department of Osteoporosis,Gansu Hospital of Traditional Chinese Medicine,Lanzhou 730050;Department of Traumatic Orthopedics,Gansu Hospital of Traditional Chinese Medicine,Lanzhou 730050)

机构地区：[1]甘肃省中医院骨质疏松科,兰州730050 [2]甘肃省中医院创伤骨一科,兰州730050

出　　处：《中药药理与临床》2019年第4期95-99,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：甘肃省自然科学基金资助项目(No.20180912R)

摘　　要：目的:探究三七总皂苷通过调控Wnt/β-catenin通路对家兔股骨头坏死的保护作用。方法:采用大剂量激素构建激素性股骨头坏死(SANFH)家兔模型成功后,随机分为模型组、洛伐他汀10 mg/kg组及三七总皂苷10、30、50 mg/kg组,6只/组,另取6只正常家兔作为正常对照组。分别灌胃给予相应药物或生理盐水,连续12周。检测家兔血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、钙(Ca)、磷(P)含量;血清超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、白细胞介素-33(IL-33)、白细胞介素-6(IL-6)含量。处死家兔,取出股骨头组织,采用HE染色观察家兔股骨头组织病理学改变及空骨陷窝率,采用Western blot法检测cl-CASP3、Bax、Bcl-2、Wnt3a、LRP5、β-catenin、RUNX2蛋白表达。结果:相比于空白对照组,模型组血清TC、TG、LDL、MDA含量及空骨陷窝率明显升高,而HDL、SOD、Ca及GSH-PX含量明显降低;相比于模型组,三七总皂苷30、50 mg/kg组及洛伐他汀血清TC、TG、LDL、MDA含量及空骨陷窝率明显降低,而HDL、SOD、Ca及GSH-PX含量明显升高。各组家兔血清P水平无明显差异。相比于空白对照组,模型组股骨头组织cl-CASP3、Bax蛋白表达上调,而Bcl-2、Wnt3a、LRP5、β-catenin、RUNX2蛋白表达明显下调;相比于模型组,三七总皂苷10、30、50 mg/kg组及洛伐他汀组股骨头组织cl-CASP3、Bax蛋白表达明显下调,而Bcl-2、Wnt3a、LRP5、β-catenin、RUNX2蛋白表达明显上调。结论:三七总皂苷可通过降低血脂、抑制炎症起到预防和缓解股骨头坏死进展的作用,而其作用机制可能与其能激活Wnt/β-catenin通路有关。Objective: To investigate the protective effect of Panax notoginseng saponins (PNS) on femoral head necrosis in rabbits by regulating Wnt/β-catenin pathway. Methods: High dose of hormones were performed to establish the rabbit models of steroid-associated necrosis of the femoral herd (SANFH). Model rabbits were randomly divided into the model group,PNS groups (10、30、50 mg/kg) and 10 mg/kg Lovastatin group,6 cases in one group,6 normal rats were set in the control group. Corresponding drugs or saline water were administered for 12 weeks,respectively. After treatment,levels of serum total cholesterol (TC),triglyceride (TG),high-density lipoprotein (HDL),low-density lipoprotein (LDL),calcium (Ca) and phosphorus (P),superoxide dismutase (SOD),glutathione peroxidase (GSH-Px),malondialdehyde (MDA),interleukin-33 (IL-33) and interleukin-6 (IL-6) in each group were measured. The rabbits were sacrificed,and femoral head tissues were collected. The pathological changes and empty bone sag rate of femoral head tissues were observed by HE staining. The protein expressions of cl-CASP3,Bax,Bcl-2,Wnt3 a,LRP5,β-catenin and RUNX2 protein were detected by RT-PCR. Results: Compared with the control group,levels of serum TC,TG,LDL,MDA and empty bone sag rate in the model group were increased,while levels of HDL,SOD,Ca and GSH-PX were decreased. Compared with the model group,levels of serum TC,TG,LDL,MDA and empty bone sag rate in PNS group (30、50 mg/kg) and the model group were decreased,while levels of HDL,SOD,Ca and GSH-PX were increased. There was no significant difference in serum P levels among the groups. Compared with the control group,protein expressions of cl-CASP3 and Bax in femoral head tissues in the model group were up regulated,expressions of Bcl-2,Wnt3 a,LRP5,β-catenin and RUNX2 protein were down regulated. Compared with the model group,protein expressions of cl-CASP3 and Bax in femoral head tissues of PNS group (10、30、50 mg/kg)and lovastatin group were down regulated,while protein expressions of Bcl-2,Wnt

关 键 词：三七总皂苷 股骨头坏死 血脂水平 氧化应激水平 促炎因子 WNT/Β-CATENIN通路 

分 类 号：R68[医药卫生—骨科学]