加味补阳还五汤对膝骨关节炎大鼠软骨细胞凋亡的影响OA
Effect of Modified Buyang Huanwu Decoction on Chondrocyte Apoptosis in Rats with Knee Osteoarthritis
目的:探讨加味补阳还五汤治疗膝骨关节炎的可能机制.方法:培养50只无特定病原体(SPF)级SD雄性大鼠,适应性饲养7 d后,随机分为假手术组、模型组、阳性药物组、加味补阳还五汤低/高剂量组,每组10只.除假手术组外,其余各组大鼠均采用改良Hulth法构建膝骨关节炎大鼠模型,造模成功2周后开始灌胃给药.阳性药物组大鼠灌胃25 mg/kg盐酸氨基葡萄糖,加味补阳还五汤低/高剂量组大鼠分别灌胃6.5,26.0 g/kg加味补阳还五汤,其余组灌胃等量生理盐水,1次/d,连续给药4周.给药结束后对各组大鼠进行Lequesne MG行为学评估,测各组大鼠机械缩足阈值,ELISA法检测血清中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的含量,苏木精-伊红(HE)染色观察右膝关节软骨组织学形态,TUNEL染色观察关节内软骨细胞凋亡,Western Blot法检测右膝关节软骨组织PI3K、Akt蛋白表达情况.结果:与假手术组相比,模型组机械缩足阈值降低,Lequesne MG行为学评分、Pelletier评分、TUNEL阳性表达、Mankin关节病理评分、TNF-α、IL-1β、IL-6、PI3K、Akt表达显著升高.与模型组相比,加味补阳还五汤处理后HE染色结果显示治疗效果很明显,机械缩足阈值明显升高,Pelletier评分、Lequesne MG行为学评分、Mankin关节病理评分、TUNEL阳性表达、TNF-α、IL-1β、IL-6、PI3K、Akt蛋白表达显著降低,差异有统计学意义(P<0.05),且加味补阳还五汤浓度越高,改善作用越明显.结论:加味补阳还五汤可改善膝骨关节炎模型大鼠膝关节软骨组织的病理形态,缓解关节疼痛,其可能的作用机制涉及对PI3K/Akt通路的抑制,减少炎症因子释放,保护骨性结构.
Objective:To investigate the potential mechanisms of modified Buyang Huanwu decoction(MBYHWD)in the treatment of knee osteoarthritis(KOA).Methods:Fifty male SPF-grade SD rats were adaptively fed for 7 d and then ran-domly divided into five groups(n=10 per group):the sham-operated group,the model group,the positive drug group,the MBYHWD low-dose group,and the MBYHWD high-dose group.Except for the sham-operated group,KOA models were established in the rats using the modified Hulth method.Two weeks after successful modeling,intragastric administration began:the positive drug group received 25 mg/kg of glucosamine hydrochloride;the MBYHWD low-dose and high-dose groups received 6.5 g/kg and 26.0 g/kg of MBYHWD,respectively;while the remaining groups received an equal volume of saline,once daily for 4 consecutive weeks.After treatment,the Lequesne MG behavioral assess-ment was performed,and the mechanical paw withdrawal threshold(MWT)was measured.Serum levels of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)were detected by ELISA.Histological morphology of the right knee cartilage was observed via HE staining,chondrocyte apoptosis within the joint was assessed by TUNEL staining,and protein expression of PI3K and Akt in the right knee cartilage tissue was detected by Western Blot.Results:Compared with the sham-operated group,the model group showed a decreased MWT and significantly increased Lequesne MG behavioral scores,Pelletier scores,TUNEL-pos-itive expression,Mankin's joint pathology scores,and expression levels of TNF-α,IL-1β,IL-6,PI3K,and Akt.Compared with the model group,MBYHWD treatment resulted in markedly improved therapeutic outcomes on HE staining,a signif-icantly increased MWT,and significantly decreased Pelletier scores,Lequesne MG behavioral scores,Mankin's scores,TUNEL-positive expression,and protein expression levels of TNF-α,IL-1β,IL-6,PI3K,and Akt(P<0.05).The im-provement was more pronounced with higher concentrations of MBYHWD.Conclusion:MBYHWD can improve the patho-logical morphology of knee cartilage and alleviate joint pain in a rat model of KOA.Its potential mechanism of action may involve inhibition of the PI3K/Akt pathway,reduction of inflammatory cytokine release,and protection of bone structures.
范旗;马辰希;董忠;潘廷明;陈会会;王和鸣
福建中医药大学附属第二人民医院(福州,350003)||福建中医药大学福建中医药大学附属第二人民医院(福州,350003)||福建中医药大学福建中医药大学福建中医药大学福建中医药大学福建省中医药科学院
医药卫生
加味补阳还五汤膝骨关节炎PI3K/Akt信号通路细胞凋亡
modified Buyang Huanwu decoctionknee osteoarthritisPI3K/Akt signaling pathwayapoptosis
《中国中医骨伤科杂志》 2026 (3)
57-64,8
福建省卫健委科技计划项目(2023CXA047)
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