文献类型：期刊文献

中文题名：藤黄健骨胶囊调控AMPK/PGC-1α信号通路改善膝骨关节炎大鼠基质代谢失衡和线粒体生物发生

英文题名：Tenghuang Jiangu Capsule Improves Imbalance of Matrix Metabolism and Mitochondrial Biogenesis in Knee Osteoarthritis Rats by Regulating the AMPK/PGC-1αSignaling Pathway

作者：颜春鲁[1,2,3];安方玉[1,2];王霞霞[1];张捷[1];宋佳眙[1];王玉洁[1];高鹏[1];常伟荣[1];贾雪茹[1];石杨洋[1];杨帆[1];肖小龙[1];苏军昌[1];肖志攀[1]

第一作者：颜春鲁

机构：[1]甘肃中医药大学,兰州730000;[2]甘肃省高校重大疾病分子医学与中医药防治研究重点实验室,兰州730000;[3]甘肃省中医药研究中心,兰州730000

第一机构：甘肃中医药大学

年份：2025

卷号：42

期号：11

起止页码：1832

中文期刊名：中国现代应用药学

外文期刊名：Chinese Journal of Modern Applied Pharmacy

收录：;北大核心:【北大核心2023】；

基金：甘肃省联合科研基金项目(24JRRA879);甘肃省教育厅高校教师创新基金项目(2025A-117、2025B-125),甘肃省教育厅研究生“创新之星”项目(2025CXZX-938);甘肃省中医药研究中心开放课题(zyzx-2024-zx16);甘肃中医药大学科学研究与创新基金项目(2023KCZD-1);甘肃中医药大学研究生教育教学研究与改革项目(2023-15)。

语种：中文

中文关键词：骨藤黄健骨胶囊;膝骨关节炎;AMPK/PGC-1α信号通路;基质代谢;线粒体生物发生

外文关键词：Tenghuang Jiangu capsule;knee osteoarthritis;AMPK/PGC-1αsignal pathway;matrix metalloproteinases;mitochondrial biogenesis

摘要：目的 探讨藤黄健骨胶囊对膝骨关节炎大鼠基质代谢的影响及分子机制。方法 60只SD大鼠随机分为假手术组、模型组、阳性药组(硫酸氨基葡萄糖胶囊0.17g·kg^(-1))及藤黄健骨胶囊高、中、低剂量治疗组(藤黄健骨胶囊0.36、0.18、0.09 g·kg^(-1)),每组10只。除假手术组外,其他各组采用改良Hulth法制备膝关节骨关节炎(knee osteoarthritis,KOA)大鼠模型,建模6周后分别灌胃给予硫酸氨基葡萄糖及相应剂量的藤黄健骨胶囊,假手术组和模型组灌胃给予0.9%生理盐水。上述药物连续灌胃2个月后采用Lequesne膝关节级别评分法评估大鼠右膝对疼痛的刺激反应步态改变、关节活动度和关节的肿胀程度,番红固绿O染色法观察关节软骨病理形态并进行OARSI评分;ELISA法检测血清中核心结合因子β亚基(corebinding factor subunit beta,Cbf-β)、基质金属蛋白酶13(matrix metalloproteinase 13,MMP-13)、组织金属蛋白酶抑制剂2(tissue inhibitor of metalloproteinase 2,TIMP-2)、Ⅱ型胶原羧基末端肽(type II collagen carboxy terminal peptide,CTX-Ⅱ)、血小板反应蛋白解整合素金属肽酶4(a disintegrin and metalloproteinase with thrombospondin 4,ADAMTS-4)和血小板反应蛋白解整合素金属肽酶5(ADAMTS-5)浓度;RT-PCR法和Western blotting观察关节软骨组织中单磷酸腺苷激活的蛋白激酶(AMP-activated protein kinase,AMPK)、过氧化物酶增殖激活受体γ共激活子-1α(peroxisome proliferator-activated receptor γ coactivator-1α,PGC-1α)、MMP-13 mRNA表达和蛋白表达。结果 与假手术组比较,模型组Lequesne MG评分呈现增加,血清Cbf-β、MMP-13、CTX-Ⅱ、ADAMTS-4、ADAMTS-5浓度明显上升,MMP-13 mRNA表达和蛋白表达则明显上升,模型组和藤黄健骨低剂量组大鼠OARSI评分也明显上升,而血清TIMP2浓度明显下降,右膝关节软骨组织PGC-1α、AMPK mRNA表达也明显下降(P<0.01)。与模型组比较,藤黄健骨胶囊高剂量组大鼠血清ADAMTS-5浓度明显下降、TIMP-2浓度明显上升(P<0.01),藤黄健骨胶囊中、高剂量组Lequesne MG评分、OARSI评分、血清Cbf-β、CTX-Ⅱ和ADAMTS-4含量均明显下降,右膝关节软骨组织PGC-1α蛋白表达及蛋白表达灰度值明显增强(P<0.05或P<0.01),藤黄健骨胶囊低、中、高剂量组大鼠血清MMP-13含量、MMP-13 mRNA表达、蛋白表达及蛋白表达灰度值明显下降,右膝关节软骨组织AMPK、PGC-1α mRNA表达明显上升,AMPK蛋白表达及蛋白表达灰度值也明显增强(P<0.01)。结论藤黄健骨胶囊延缓KOA模型大鼠的关节软骨退变可能与维持其关节软骨组织基质代谢稳态和逆转线粒体生物发生损伤有关,其中AMPK/PGC-1α信号通路激活可能发挥着关键调控作用。
OBJECTIVE To investigate the effect of the Tenghuang Jiangu capsule on matrix metabolism in rats with knee osteoarthritis and its molecular mechanism.METHODS Sixty SD rats were randomly divided into the sham operation group,model group,positive control group(glucosamine sulfate:0.17 g·kg^(-1)),and high-,middle-,and low-dose treatment groups(Tenghuang Jiangu capsule:0.36,0.18,0.09 g·kg^(-1)),with 10 rats in each group.Knee osteoarthritis(KOA)rat model was made using a modified version of the Hulth method,excluding the sham operation group.After 6 weeks of modelling,glucosamine sulfate and the corresponding dosage of the Tenghuang Jiangu capsule were administered through the stomach,and 0.9%normal saline was administered through the stomach in the sham operation group and the model group.After 2 months of continuous intragastric administration of the above drugs,the knee joint grade of rats was observed using the Lequesne knee joint grade score;the gait change,joint range of motion,and joint swelling degree of rats were evaluated with the Lequesne knee joint grade score,the pathological morphology of the joint cartilage was observed through saffron solid green O staining,and preform quantitative OARSI scoring.Serum concentrations of core-binding factor subunit beta(Cbf-β),matrix metalloproteinase 13(MMP-13),tissue inhibitor of metalloproteinase 2(TIMP-2),typeⅡcollagen terminal peptide(CTX-Ⅱ),platelet reactive protein disintegrin metallopeptidase 4(ADAMTS-4),and platelet reactive protein disintegrin metallopeptidase 5(ADAMTS-5)were detected by ELISA.The expression of AMP-activated protein kinase(AMPK),peroxidase proliferator-activated receptorγcoactivator 1α(PGC-1α),MMP-13 mRNA and protein in the articular cartilage were observed with RT-PCR and Western blotting.RESULTS Compared with the sham-operated group,the serum Cbf-β,MMP-13,CTX-Ⅱ,ADAMTS-4,and ADAMTS-5 concentrations,and the MMP-13 mRNA and protein expression levels significant increased in the model group,the Lequesne MG score and the OARSI score also increased in the model group and low-dose groups,but serum TIMP-2 concentration significant decreased in the model group.The expression levels of PGC-1αand AMPK mRNA in the cartilage of the right knee joint also exhibited a downward trend(P<0.01).Compared with the model group,the concentration of ADAMTS-5 and TIMP-2 in the high-dose group exhibited a downward trend,while the TIMP-2 concentration exhibited an upward trend(P<0.01).The Lequesne MG score,OARSI score,and Cbf-β,CTX-Ⅱ,and ADAMTS-4 levels in the middle-and high-dose groups all showed a downward trend.The expression of the PGC-1αprotein and its grey value in the cartilage tissue of the right knee joint exhibited an increasing trend(P<0.05 or P<0.01).The content of MMP-13 and MMP-13 mRNA,and protein expression in the low-,middle-,and high-dose groups of Tenghuang Jiangu capsule exhibited a downward trend,and the expression levels of AMPK and the PGC-1αmRNA in the cartilage tissue of the right knee joint also increased,the expression of the AMPK protein and its grey value in the cartilage tissue of the right knee joint exhibited an increasing trend(P<0.05 or P<0.01).CONCLUSION Tenghuang Jiangu capsule delays the degeneration of the articular cartilage in KOA model rats,which may be related to maintaining the homeostasis of the articular cartilage matrix and reversing the damage of mitochondrial biogenesis,and the activation of the AMPK/PGC-1αsignal pathway may play a key regulatory role.