[1]阮张德阳,王上增,程韶,等.加味补肾壮筋汤治疗小鼠膝骨关节炎的效果和作用机制研究[J].中医正骨,2026,38(06):13-25,37.
　RUAN-ZHANG Deyang,WANG Shangzeng,CHENG Shao,et al.Efficacy and mechanism of Jiawei Bushen Zhuangjin Tang(加味补肾壮筋汤)against knee osteoarthritis in mice[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2026,38(06):13-25,37.
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加味补肾壮筋汤治疗小鼠膝骨关节炎的效果和作用机制研究()

《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第38卷
期数:
2026年06期
页码:
13-25,37
栏目:
基础研究
出版日期:
2026-06-20

文章信息/Info

Title:
Efficacy and mechanism of Jiawei Bushen Zhuangjin Tang(加味补肾壮筋汤)against knee osteoarthritis in mice
作者:
阮张德阳1; 王上增2; 程韶2; 马金昕1; 马龙飞1; Huynh Anh Kiet3
1.河南中医药大学国际教育学院,河南 郑州 450046; 2.河南省中医院,河南 郑州 450002; 3.Dong Thap Medical College,Dong Thap Cao Lanh 81000
Author(s):
RUAN-ZHANG Deyang1; WANG Shangzeng2; CHENG Shao2; MA Jinxin1; MA Longfei1; Huynh Anh Kiet3
1.School of International Education,Henan University of Chinese Medicine,Zhengzhou 450046,Henan,China; 2.Henan Province Hospital of TCM,Zhengzhou 450002,Henan,China; 3.Dong Thap Medical College,Cao Lanh 81000,Dong Thap,Vietnam
关键词:
骨关节炎; 膝;  加味补肾壮筋汤;  泛凋亡;  小鼠;  软骨细胞
Keywords:
osteoarthritis; knee;  Jiawei Bushen Zhuangjin Tang;  PANoptosis;  mice;  chondrocytes
摘要:
目的:探讨加味补肾壮筋汤治疗小鼠膝骨关节炎(knee osteoarthritis,KOA)的效果和作用机制。方法:①动物实验。将54只8周龄雄性C57BL/6J小鼠随机分为假手术组、模型组、塞来昔布组及加味补肾壮筋汤低、中、高剂量组,每组9只。除假手术组外,其余各组小鼠均采用内侧半月板胫骨韧带离断法建立右侧KOA模型。造模后1周,加味补肾壮筋汤低、中、高剂量组小鼠分别按照生药量4.5 g·kg-1·d-1、9.0 g·kg-1·d-1、13.5 g·kg-1·d-1以加味补肾壮筋汤药液灌胃,塞来昔布组小鼠按照30 mg·kg-1·d-1以塞来昔布混悬液灌胃,假手术组小鼠每日以等体积生理盐水灌胃。连续干预8周后,检测小鼠血清C-X-C基序趋化因子配体1(C-X-C motif chemokine ligand 1,CXCL1)、白细胞介素(interleukin,IL)-6、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和IL-1β的水平; 制备小鼠膝关节组织切片,观察软骨组织病理改变,采用国际骨关节炎研究协会(Osteoarthritis Research Society International,OARSI)骨关节炎组织学评分系统评价小鼠膝关节软骨退变程度; 检测小鼠膝关节软骨组织中Z-DNA结合蛋白1(Z-DNA binding protein 1,ZBP1)、黑色素瘤缺失因子2(absent in melanoma 2,AIM2)、核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3(nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3,NLRP3)、消皮素D(gasdermin D,GSDMD)、活化的半胱氨酸天冬氨酸蛋白酶(cleaved cysteine aspartic acid specific protease,c-caspase)-1、c-caspase-3、c-caspase-8、受体相互作用蛋白激酶(receptor-interacting protein kinase,RIPK)1、RIPK3的蛋白相对表达量及RIPK1、RIPK3磷酸化水平。②细胞实验。从3周龄SPF级雄性C57BL/6J小鼠分离膝关节透明软骨组织,培养、传代后取第1代软骨细胞,分为模型组、加味补肾壮筋汤干预组、ZBP1过表达组和加味补肾壮筋汤干预联合ZBP1过表达组。模型组、加味补肾壮筋汤干预组软骨细胞转染空载体pcDNA3.1,ZBP1过表达组和加味补肾壮筋汤干预联合ZBP1过表达组软骨细胞转染ZBP1过表达载体pcDNA3.1-ZBP1; 转染并同步化后,各组软骨细胞均加入终浓度为10 ng·mL-1的IL-1β,同时加味补肾壮筋汤干预组、加味补肾壮筋汤干预联合ZBP1过表达组软骨细胞加入终浓度为0.2 g·mL-1(生药量)的加味补肾壮筋汤药液。继续培养48 h后,检测各组软骨细胞活力与凋亡率及ZBP1、c-caspase-1、GSDMD、c-caspase-8、c-caspase-3的蛋白相对表达量。结果:①动物实验。加味补肾壮筋汤低剂量组小鼠血清CXCL1、IL-6水平与模型组的差异无统计学意义(P=1.000,P=0.124),加味补肾壮筋汤中、高剂量组及塞来昔布组小鼠血清CXCL1、IL-6水平均低于模型组(CXCL1:P=0.007,P=0.000,P=0.000; IL-6:P=0.002,P=0.000,P=0.000); 加味补肾壮筋汤中、高剂量组小鼠血清CXCL1水平均低于加味补肾壮筋汤低剂量组(P=0.011,P=0.000); 加味补肾壮筋汤高剂量组小鼠血清CXCL1水平低于加味补肾壮筋汤中剂量组(P=0.000); 加味补肾壮筋汤低、中、高剂量组小鼠血清IL-6水平两两比较,差异均无统计学意义; 塞来昔布组小鼠血清CXCL1、IL-6水平均低于加味补肾壮筋汤低、中剂量组(CXCL1:P=0.000,P=0.023; IL-6:P=0.000,P=0.000),与加味补肾壮筋汤高剂量组的差异均无统计学意义。加味补肾壮筋汤低、中、高剂量组及模型组小鼠血清TNF-α水平两两比较,差异均无统计学意义; 塞来昔布组小鼠血清TNF-α水平低于模型组及加味补肾壮筋汤低、中、高剂量组(P=0.000,P=0.000,P=0.000,P=0.000)。除假手术组之外,其余5组小鼠血清IL-1β水平两两比较,差异均无统计学意义。模型组小鼠膝关节软骨表面粗糙、缺损,软骨细胞排列紊乱、簇集,潮线模糊或中断,软骨基质染色较浅; 与模型组相比,加味补肾壮筋汤低剂量组小鼠膝关节上述病理表现略有改善,加味补肾壮筋汤中剂量组进一步改善,加味补肾壮筋汤高剂量组和塞来昔布组明显改善,且这2组的病理表现改善情况相当。加味补肾壮筋汤低剂量组小鼠膝关节OARSI评分与模型组的差异无统计学意义,加味补肾壮筋汤中、高剂量组及塞来昔布组小鼠膝关节OARSI评分均低于模型组(P=0.001,P=0.000,P=0.000)和加味补肾壮筋汤低剂量组(P=0.001,P=0.000,P=0.000); 加味补肾壮筋汤中、高剂量组及塞来昔布组小鼠膝关节OARSI评分两两比较,差异均无统计学意义。6组小鼠软骨组织中RIPK1和RIPK3的蛋白相对表达量总体比较的差异无统计学意义。加味补肾壮筋汤低剂量组小鼠软骨组织中ZBP1的蛋白相对表达量及RIPK1、RIPK3磷酸化水平均低于模型组(P=0.028,P=0.016,P=0.010),AIM2、NLRP3、GSDMD、c-caspase-1、c-caspase-3、c-caspase-8的蛋白相对表达量与模型组的差异均无统计学意义; 加味补肾壮筋汤中剂量组小鼠软骨组织中ZBP1、AIM2、GSDMD、c-caspase-3的蛋白相对表达量及RIPK1、RIPK3磷酸化水平均低于模型组(P=0.000,P=0.004,P=0.001,P=0.000,P=0.000,P=0.000),NLRP3、c-caspase-1、c-caspase-8的蛋白相对表达量与模型组的差异均无统计学意义; 加味补肾壮筋汤高剂量组、塞来昔布组小鼠软骨组织中ZBP1、AIM2、NLRP3、GSDMD、c-caspase-1、c-caspase-3、c-caspase-8的蛋白相对表达量及RIPK1、RIPK3磷酸化水平均低于模型组(P=0.000,P=0.000,P=0.000,P=0.000,P=0.000,P=0.000,P=0.006,P=0.000,P=0.000; P=0.000,P=0.000,P=0.000,P=0.000,P=0.000,P=0.000,P=0.000,P=0.000,P=0.000)。加味补肾壮筋汤中剂量组小鼠软骨组织中GSDMD、c-caspase-3的蛋白相对表达量及RIPK3磷酸化水平均低于加味补肾壮筋汤低剂量组(P=0.003,P=0.000,P=0.044),ZBP1、AIM2、NLRP3、c-caspase-1、c-caspase-8的蛋白相对表达量及RIPK1磷酸化水平与加味补肾壮筋汤低剂量组的组间差异均无统计学意义; 加味补肾壮筋汤高剂量组、塞来昔布组小鼠软骨组织中ZBP1、AIM2、NLRP3、GSDMD、c-caspase-1、c-caspase-3、c-caspase-8的蛋白相对表达量及RIPK1、RIPK3磷酸化水平均低于加味补肾壮筋汤低剂量组(P=0.001,P=0.011,P=0.000,P=0.000,P=0.014,P=0.000,P=0.000,P=0.002,P=0.001; P=0.000,P=0.000,P=0.000,P=0.000,P=0.000,P=0.000,P=0.001,P=0.000,P=0.000)。加味补肾壮筋汤高剂量组小鼠软骨组织中ZBP1、NLRP3、c-caspase-3、c-caspase-8的蛋白相对表达量及RIPK1磷酸化水平均低于加味补肾壮筋汤中剂量组(P=0.044,P=0.007,P=0.020,P=0.006,P=0.022),AIM2、GSDMD、c-caspase-1的蛋白相对表达量及RIPK3磷酸化水平与加味补肾壮筋汤中剂量组的组间差异均无统计学意义; 塞来昔布组小鼠软骨组织中ZBP1、AIM2、NLRP3、c-caspase-1、c-caspase-3、c-caspase-8的蛋白相对表达量及RIPK1、RIPK3磷酸化水平均低于加味补肾壮筋汤中剂量组(P=0.000,P=0.016,P=0.000,P=0.006,P=0.014,P=0.001,P=0.001,P=0.033),GSDMD的蛋白相对表达量与加味补肾壮筋汤中剂量组的差异无统计学意义。塞来昔布组小鼠软骨组织中ZBP1、AIM2、NLRP3、GSDMD、c-caspase-1、c-caspase-3、c-caspase-8的蛋白相对表达量及RIPK1、RIPK3磷酸化水平与加味补肾壮筋汤高剂量组的组间差异均无统计学意义。②细胞实验。模型组、加味补肾壮筋汤干预组、加味补肾壮筋汤干预联合ZBP1过表达组软骨细胞活力均高于ZBP1过表达组(P=0.000,P=0.000,P=0.000),凋亡率均低于ZBP1过表达组(P=0.000,P=0.000,P=0.000); 加味补肾壮筋汤干预组、加味补肾壮筋汤干预联合ZBP1过表达组软骨细胞活力均高于模型组(P=0.006,P=0.000),凋亡率均低于模型组(P=0.000,P=0.000); 加味补肾壮筋汤干预联合ZBP1过表达组软骨细胞活力低于加味补肾壮筋汤干预组(P=0.000),凋亡率高于加味补肾壮筋汤干预组(P=0.000)。加味补肾壮筋汤干预组软骨细胞中GSDMD、c-caspase-1、c-caspase-3、c-caspase-8蛋白相对表达量均低于模型组(P=0.000,P=0.006,P=0.003,P=0.004),ZBP1蛋白相对表达量与模型组的差异无统计学意义; ZBP1过表达组软骨细胞中ZBP1、GSDMD、c-caspase-1、c-caspase-3、c-caspase-8蛋白相对表达量均高于模型组(P=0.000,P=0.000,P=0.002,P=0.000,P=0.003); 加味补肾壮筋汤干预联合ZBP1过表达组软骨细胞中ZBP1蛋白相对表达量高于模型组(P=0.000),GSDMD、c-caspase-1、c-caspase-3、c-caspase-8蛋白相对表达量与模型组的差异均无统计学意义。加味补肾壮筋汤干预组软骨细胞中ZBP1、c-caspase-1、GSDMD、c-caspase-3、c-caspase-8蛋白相对表达量均低于ZBP1过表达组(P=0.000,P=0.000,P=0.000,P=0.000,P=0.000); 加味补肾壮筋汤干预联合ZBP1过表达组软骨细胞中c-caspase-1、GSDMD、c-caspase-3、c-caspase-8蛋白相对表达量均低于ZBP1过表达组(P=0.000,P=0.000,P=0.000,P=0.001),ZBP1蛋白相对表达量与ZBP1过表达组的差异无统计学意义。加味补肾壮筋汤干预联合ZBP1过表达组软骨细胞中ZBP1、GSDMD、c-caspase-1、c-caspase-3、c-caspase-8蛋白相对表达量均高于加味补肾壮筋汤干预组(P=0.000,P=0.002,P=0.041,P=0.047,P=0.022)。结论:加味补肾壮筋汤能够缓解KOA小鼠的炎症反应,且针对部分促炎性细胞因子具有剂量依赖性; 加味补肾壮筋汤能够缓解KOA小鼠的软骨退变,且中高剂量加味补肾壮筋汤的效果更显著,与塞来昔布相当; 加味补肾壮筋汤治疗KOA的作用机制与通过抑制泛凋亡相关信号通路减少软骨细胞死亡密切相关,且ZBP1可能是其发挥软骨细胞保护作用的关键靶点。
Abstract:
Objective:To investigate the therapeutic efficacy of Jiawei Bushen Zhuangjin Tang(加味补肾壮筋汤,JBZT)against knee osteoarthritis(KOA)in mice,and to explore its underlying molecular mechanisms.Methods:①Animal experiment.Fifty-four 8-week-old male C57BL/6J mice were selected and randomized into a sham-operated group,a model group,a celecoxib group,a low-dose JBZT(L-JBZT)group,a medium-dose JBZT(M-JBZT)group,and a high-dose JBZT(H-JBZT)group,with 9 ones in each group.All mice but the ones in sham-operated group were subjected to medial meniscotibial ligament transection(MMTLT)on the right knee joints to induce KOA,while the ones in sham-operated group were merely incised the medial skin and subcutaneous tissues to expose the knee joint cavity at the corresponding sites and then sutured.One week after successful modeling,the mice in the L-,M-,and H-JBZT groups were intervened by intragastric administration with JBZT solution at crude drug dosages of 4.5,9.0,and 13.5 g/kg/day,respectively; the ones in celecoxib group with celecoxib suspension at a dose of 30 mg/kg/day; and the ones in the sham-operated group with an equal volume of normal saline every day for consecutive 8 weeks.Following the end of intervention,the blood was drawn and the knee cartilage tissues were harvested from the mice in each group for the following analyses:the serum levels of C-X-C motif chemokine ligand 1(CXCL1),interleukin(IL)-6,tumor necrosis factor-α(TNF-α),and IL-1β were measured; the histopathological changes of the knee joint cartilage were examined by observing the prepared knee joint sections under a microscope,and the severity of cartilage degeneration was then assessed using the Osteoarthritis Research Society International(OARSI)histological scoring system; furthermore,the relative protein expression levels of Z-DNA binding protein 1(ZBP1),absent in melanoma 2(AIM2),nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3),gasdermin D(GSDMD),cleaved cysteine aspartic acid specific protease(c-caspase)-1,c-caspase-3,c-caspase-8,receptor-interacting protein kinase(RIPK)1,and RIPK3,as well as the phosphorylation levels of RIPK1 and RIPK3,in the mice knee joint cartilage tissues were detected.②Cell experiment.The knee articular hyaline cartilage tissues were harvested from the 3-week-old SPF-grade male C57BL/6J mice,and the primary chondrocytes were isolated from the knee articular hyaline cartilage tissues.After cultivation and passaging,the passage 1(P1)chondrocytes were divided into a model group,a JBZT intervention group,a ZBP1-overexpression(OE)group,and a JBZT intervention combined with ZBP1-OE group.The P1 chondrocytes in the model group and JBZT intervention group were transfected with the empty vector pcDNA3.1,while those in the ZBP1-OE group and JBZT intervention combined with ZBP1-OE group with the ZBP1-OE vector pcDNA3.1-ZBP1.Following the transfection and synchronization,the chondrocytes in all groups were stimulated with IL-1β at a final concentration of 10 ng/mL,meanwhile,those in JBZT intervention group and JBZT intervention combined with ZBP1-OE group were treated with JBZT decoction at a final concentration of 0.2 g/mL(crude drug).After further culture for 48 hours,the chondrocyte viability and apoptosis rate,as well as the relative protein expression levels of ZBP1,c-caspase-1,GSDMD,c-caspase-8,and c-caspase-3,were detected in each group.Results:①Findings from animal experiment.Compared with the model group,the L-JBZT group showed no significant diffe-rences in serum CXCL1 or IL-6 levels(P=1.000,P=0.124),whereas the M-JBZT group,H-JBZT group and celecoxib group all exhibited significantly lower serum levels of both CXCL1 and IL-6(CXCL1:P=0.007,P=0.000,P=0.000; IL-6:P=0.002,P=0.000,P=0.000).The serum CXCL1 level was lower in the M- and H-JBZT groups compared to the L-JBZT group(P=0.011,P=0.000),and was lowest in H-JBZT group(P=0.000).However,pairwise comparisons of serum IL-6 level among the L-,M-,and H-JBZT groups revealed no significant differences.The serum CXCL1 and IL-6 levels were lower in celecoxib group compared to L- and M-JBZT groups(CXCL1:P=0.000,P=0.023; IL-6:P=0.000,P=0.000),but showed no significant difference compared to H-JBZT group.Pairwise comparisons of serum TNF-α level among the model group and L-,M-,and H-JBZT groups revealed no significant differences.However,the serum TNF-α level was significantly lower in the celecoxib group compared to the model group and all three JBZT groups(P=0.000,P=0.000,P=0.000,P=0.000).Besides,pairwise comparisons of serum IL-1β level across the five groups(except for the sham-operated group)revealed no statistically significant differences.Histopathologically,in the model group,the knee joint cartilage surfaces were rough and defective,with chondrocytes arranged in a disordered and clustered pattern,the tidemarks indistinct or interrupted,and the cartilage matrix staining diminished; compared with the model group,these pathological alterations were mildly alleviated in the L-JBZT group,further improved in the M-JBZT group,and markedly improved in both the H-JBZT group and the celecoxib group,with comparable improvement degrees observed between the latter two groups.The knee joint OARSI score in the L-JBZT group was not significantly different from that in the model group,while,it was significantly lower in the M-JBZT group,H-JBZT group and celecoxib group compared to the model group or the L-JBZT group(P=0.001,P=0.000,P=0.000; P=0.001,P=0.000,P=0.000),with no significant differences observed among the M-JBZT group,H-JBZT group and celecoxib group.Regarding the PANoptosis-related proteins,the relative protein expression levels of RIPK1 and RIPK3 in cartilage tissue revealed no statistically significant differences among the six groups.In the L-JBZT group,the relative protein expression level of ZBP1,as well as the phosphorylation levels of RIPK1 and RIPK3,in cartilage tissues were significantly lower than those in the model group(P=0.028,P=0.016,P=0.010),whereas the relative protein expression levels of AIM2,NLRP3,GSDMD,c-caspase-1,c-caspase-3,and c-caspase-8 showed no significant differences compared with the model group.In the M-JBZT group,the relative protein expression levels of ZBP1,AIM2,GSDMD,and c-caspase-3,as well as the phosphorylation levels of RIPK1 and RIPK3,were significantly lower than those in the model group(P=0.000,P=0.004,P=0.001,P=0.000,P=0.000,P=0.000),while the relative protein expression levels of NLRP3,c-caspase-1,and c-caspase-8 showed no significant differences compared with the model group.In the H-JBZT group and celecoxib group,the relative protein expression levels of ZBP1,AIM2,NLRP3,GSDMD,c-caspase-1,c-caspase-3,and c-caspase-8,as well as the phosphorylation levels of RIPK1 and RIPK3,were all lower than those in the model group(P=0.000,P=0.000,P=0.000,P=0.000,P=0.000,P=0.000,P=0.006,P=0.000,P=0.000; P=0.000,P=0.000,P=0.000,P=0.000,P=0.000,P=0.000,P=0.000,P=0.000,P=0.000).In the M-JBZT group,the relative protein expression levels of GSDMD and c-caspase-3,as well as the phosphorylation level of RIPK3,in cartilage tissues,were significantly lower than those in the L-JBZT group(P=0.003,P=0.000,P=0.044),while the relative protein expression levels of ZBP1,AIM2,NLRP3,c-caspase-1,and c-caspase-8,as well as the phosphorylation level of RIPK1,were not significantly different between these two groups.In the H-JBZT group and celecoxib group,the relative protein expression levels of ZBP1,AIM2,NLRP3,GSDMD,c-caspase-1,c-caspase-3,and c-caspase-8,as well as the phosphorylation levels of RIPK1 and RIPK3,were all significantly lower than those in the L-JBZT group(P=0.001,P=0.011,P=0.000,P=0.000,P=0.014,P=0.000,P=0.000,P=0.002,P=0.001; P=0.000,P=0.000,P=0.000,P=0.000,P=0.000,P=0.000,P=0.001,P=0.000,P=0.000).Compared with the M-JBZT group,the relative protein expression levels of ZBP1,NLRP3,c-caspase-3,and c-caspase-8,as well as the phosphorylation level of RIPK1 were significantly lower in the H-JBZT group(P=0.044,P=0.007,P=0.020,P=0.006,P=0.022),whereas the relative protein expression levels of AIM2,GSDMD,and c-caspase-1,as well as the phosphorylation level of RIPK3 showed no significant differences between the two groups.In the celecoxib group,the relative protein expression levels of ZBP1,AIM2,NLRP3,c-caspase-1,c-caspase-3,and c-caspase-8,as well as the phosphorylation levels of RIPK1 and RIPK3,were significantly lower than those in the M-JBZT group(P=0.000,P=0.016,P=0.000,P=0.006,P=0.014,P=0.001,P=0.001,P=0.033),while the relative protein expression level of GSDMD showed no significant difference between the 2 groups.Furthermore,the relative protein expression levels of ZBP1,AIM2,NLRP3,GSDMD,c-caspase-1,c-caspase-3,and c-caspase-8,as well as the phosphorylation levels of RIPK1 and RIPK3,in the celecoxib group showed no significant differences compared with the H-JBZT group.②Findings from cell experiment.Compared with the ZBP1-OE group,the model group,JBZT intervention group,and JBZT intervention combined with ZBP1-OE group exhibited significantly higher chondrocyte viability and lower apoptosis rate(P=0.000,P=0.000,P=0.000; P=0.000,P=0.000,P=0.000).Compared with the model group,the JBZT intervention group and JBZT intervention combined with ZBP1-OE group also exhibited significantly higher chondrocyte viability and lower apoptosis rate(P=0.006,P=0.000; P=0.000,P=0.000).Compared with the JBZT intervention group,the JBZT intervention combined with ZBP1-OE group exhibited significantly lower chondrocyte viability and higher apoptosis rate(P=0.000; P=0.000).Regarding the PANoptosis-related proteins,the protein expression analysis revealed that,in the JBZT intervention group,the relative protein expression levels of GSDMD,c-caspase-1,c-caspase-3,and c-caspase-8 in chondrocytes were significantly lower than those in the model group(P=0.000,P=0.006,P=0.003,P=0.004),while the relative protein expression levels of ZBP1 showed no significant difference between the two groups.In the ZBP1-OE group,the relative protein expression levels of ZBP1,GSDMD,c-caspase-1,c-caspase-3,and c-caspase-8 in chondrocytes were all higher than those in the model group(P=0.000,P=0.000,P=0.002,P=0.000,P=0.003).In the JBZT intervention combined with ZBP1-OE group,the relative protein expression level of ZBP1 in chondrocytes was higher than that in the model group(P=0.000),however,the relative protein expression levels of GSDMD,c-caspase-1,c-caspase-3,and c-caspase-8 showed no significant difference between the two groups.Furthermore,compared with the ZBP1-OE group,the relative protein expression levels of ZBP1,c-caspase-1,GSDMD,c-caspase-3,and c-caspase-8 in chondrocytes were all lower in the JBZT intervention group(P=0.000,P=0.000,P=0.000,P=0.000,P=0.000),and the relative protein expression levels of c-caspase-1,GSDMD,c-caspase-3,and c-caspase-8 in chondrocytes were also lower in the JBZT intervention combined with ZBP1-OE group(P=0.000,P=0.000,P=0.000,P=0.001),but the relative protein expression level of ZBP1 showed no significant difference between the two groups; whereas,compared with the JBZT intervention group,the JBZT intervention combined with ZBP1-OE group showed higher relative protein expression levels of ZBP1,GSDMD,c-caspase-1,c-caspase-3,and c-caspase-8 in chondrocytes(P=0.000,P=0.002,P=0.041,P=0.047,P=0.022).Conclusion:JBZT can alleviate the inflammatory response in KOA mice,exhibiting a dose-dependent effect on specific pro-inflammatory cytokines.In addition,JBZT can effectively mitigate cartilage degeneration in KOA mice,with medium and high doses demonstrating superior efficacy comparable to celecoxib.It may exert its anti-KOA effects through reducing chondrocyte death via inhibiting PANoptosis-related signaling pathways,and ZBP1 may serve as a pivotal molecular target for its chondroprotective action.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金项目(82374490); 河南省重点研发专项(241111311700); 河南省高校科技创新团队支持计划项目(24IRTSTHN040); 河南省中青年卫生健康科技创新领军人才培养项目(LJRC2024020); 河南中医药大学“仲景三名人才工程”项目(河中医政〔2025〕116号)
通信作者:王上增 E-mail:wangsz74@163.com
(收稿日期:2026-02-14 本文编辑:吕宁)
更新日期/Last Update: 2026-06-20