[1]王鹏光,李逸统,热米拉·艾买提,等.补肾痹通方调控Hippo/YAP通路治疗膝骨关节炎大鼠的作用机制[J].中国中医骨伤科杂志,2026,34(03):7-15.[doi:10.20085/j.cnki.issn1005-0205.260302]
　WANG Pengguang,LI Yitong,REMILA Aimaiti,et al.Study on the Mechanism of Bushen Bitong Formula in Regulating the Hippo/YAP Pathway to Treat Knee Osteoarthritis in Rats[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2026,34(03):7-15.[doi:10.20085/j.cnki.issn1005-0205.260302]
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补肾痹通方调控Hippo/YAP通路治疗膝骨关节炎大鼠的作用机制()

《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第34卷
期数:
2026年03期
页码:
7-15
栏目:
基础研究
出版日期:
2026-03-15

文章信息/Info

Title:
Study on the Mechanism of Bushen Bitong Formula in Regulating the Hippo/YAP Pathway to Treat Knee Osteoarthritis in Rats
文章编号:
1005-0205(2026)03-0007-09
作者:
王鹏光1 ; 李逸统1; 热米拉·艾买提1; 牟利民1; 方锐2△
1新疆医科大学第四临床医学院(乌鲁木齐,830000); 2新疆医科大学附属中医医院
Author(s):
WANG Pengguang1; LI Yitong1; REMILA Aimaiti1; MOU Limin1; FANG Rui2△
1Fourth Clinical Medical College,Xinjiang Medical University,Urumqi 830000,China; 2Affiliated Hospital of Traditional Chinese Medicine,Xinjiang Medical University,Urumqi 830000,China.
关键词:
膝骨关节炎;  补肾痹通方;  河马信号通路;  关节软骨;  软骨基质
Keywords:
knee osteoarthritis;  Bushen Bitong formula;  Hippo signaling pathway;  articular cartilage;  cartilage matrix
分类号:
R285.5
DOI:
10.20085/j.cnki.issn1005-0205.260302
文献标志码:
A
摘要:
目的:探讨补肾痹通方调控Hippo/YAP信号通路对膝骨关节炎大鼠软骨细胞凋亡的影响。方法:将60只体重200 g左右的SD大鼠,采用随机数字表法分为补肾痹痛方低剂量组(BSBTF-L组,21.25 g/kg)、补肾痹痛方高剂量组(BSBTF-H组,42.50 g/kg)、补肾痹痛方高剂量(42.50 g/kg)+VTPF(YAP抑制剂,10 mg/kg)组、假手术组、模型组,每组各12只; 用Huhth法诱导大鼠膝骨关节炎模型,造模4周后开始灌胃给药4周,观察大鼠一般生活情况和X线检查结果; HE染色和番红O固绿染色观察膝关节软骨组织病变情况; 采用ELISA法检测血清中白细胞介素6(IL-6)、白细胞介素1β(IL-1β)与肿瘤坏死因子α(TNF-α)水平; 免疫组化检测p-YAP、YAP蛋白表达; qPCR法检测膝关节软骨组织中YAP、ADAMTS-5、MMP-13有关的mRNA表达水平; Western Blot法检测p-YAP、YAP、CTGF蛋白表达。结果:与假手术组相比,模型组大鼠精神不振,运动量小,纳差; X线检查结果表明关节间隙明显变窄甚至消失,胫骨平台表面变粗糙,股骨远端硬化,伴有骨赘形成,软骨组织严重破坏; p-YAP蛋白表达降低,IL-1β、IL-6、TNF-α水平,YAP、CTGF蛋白表达增加,差异有统计学意义(P<0.05)。与模型组相比,BSBTF-L组和BSBTF-H组对应指标的变化趋势与上述情况相反,差异有统计学意义(P<0.05),并且剂量越高,效果越明显。与补肾痹痛方高剂量组相比,补肾痹痛方高剂量+VTPF组的YAP和p-YAP表达量几乎无变化,但IL-1β、IL-6、TNF-α水平,ADAMTS-5、MMP-13有关的mRNA表达水平及CTGF蛋白表达降低,差异有统计学意义(P<0.05)。结论:补肾痹通方可能通过激活Hippo/YAP信号通路来延缓膝骨关节炎大鼠的软骨退化。
Abstract:
Objective:To investigate the effects of Bushen Bitong formula(BSBTF)on chondrocyte apoptosis in knee osteoarthritis(KOA)rats by modulating the Hippo/YAP signaling pathway.Methods:Sixty SD rats weighing approximately 200 g were randomly assigned using a random number table to the following groups:low-dose BSBTF group(BSBTF-L,21.25 g/kg),high-dose BSBTF group(BSBTF-H,42.50 g/kg),high-dose BSBTF(42.50 g/kg)+VTPF(YAP inhibitor 10 mg/kg)group,sham-operated group,and model group,with 12 rats per group.The Huhth method was used to induce a rat knee osteoarthritis model.After 4 weeks of modeling,oral administration began for 4 weeks.General daily activities and radiographic examinations were observed.Hematoxylin-eosin(HE)staining and Alcian blue staining were performed to examine knee cartilage tissue lesions.Serum levels of interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)were detected using ELISA; Immunohistochemistry assessed p-YAP and YAP protein expression; qPCR measured mRNA expression levels of YAP,ADAMTS-5,and MMP-13 in knee cartilage tissue; Western Blot analysis was used to detect p-YAP,YAP,and CTGF protein expression.Results:Compared with the sham-operated group,rats in the model group exhibited lethargy,reduced activity,and poor appetite.Radiographic examination revealed marked narrowing or even disappearance of the joint space,roughening of the tibial plateau surface,sclerosis of the distal femur,and osteophyte formation,with severe cartilage tissue destruction.p-YAP protein expression decreased,while IL-1β,IL-6,TNF-α levels,and YAP/CTGF protein expression increased(P<0.05).Compared to the model group,the BSBTF-L and BSBTF-H groups exhibited opposite trends in these indicators(P<0.05),with higher doses yielding more pronounced effects.Compared to the high-dose BSBTF group,the high-dose BSBTF+VTPF group showed minimal changes in YAP and p-YAP expression.However,IL-1β,IL-6,TNF-α levels,mRNA expression levels related to ADAMTS-5 and MMP-13,and CTGF protein expression were significantly reduced(P<0.05).Conclusion:BSBTF may delay cartilage degeneration in KOA rats by activating the Hippo/YAP signaling pathway.

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(收稿日期:2025-09-12)

备注/Memo

备注/Memo:
基金项目:国家自然科学基金地区科学基金项目(82360934)
新疆维吾尔自治区科学技术厅科技创新领军人才
项目—高层次领军人才项目(2022TSYCLJ0007)
△通信作者 E-mail:1628738966@qq.com
更新日期/Last Update: 2026-03-15