现代中西医结合杂志2025，Vol.34Issue(8)：1035-1042,8.DOI:10.3969/j.issn.1008-8849.2025.08.003
基于ASK1/JNK信号通路探究益气化瘀方抑制冻结肩关节囊纤维化的机制
Decoction for replenishing Qi and resolving stasis inhibits joint cystic fibrosis in frozen shoulder via ASK1/JNK signaling pathway
摘要
Abstract
Objective It is to explore the therapeutic mechanism of decoction for replenishing Qi and resolving stasis in inhibiting cystic fibrosis in frozen shoulder based on apoptosis signal-regulating kinase1(ASK1)/c-Jun N-terminal kinase(JNK)signaling pathway.Methods Forty male SD rats were randomly divided into control group,model group,low and high dose groups of decoction for replenishing Qi and resolving stasis,with 10 rats in each group.The rats of all groups ex-cept for the control group were prepared to establish models of frozen shoulder.On the next day after modeling,the low and high dose groups of decoction for replenishing Qi and resolving stasis were given 0.9 mL and 1.8 mL of decoction for re-plenishing Qi and resolving stasis by gavage,respectively,and the blank group and model group were given equal volume of normal saline by gavage,all once daily,continuously treated for 8 weeks.The levels of serum interleukin-1(IL-1)and tumor necrosis factor-α(TNF-α)were measured by ELISA method,the histopathological structure of shoulder joint capsule was observed by HE staining,the positive protein expressions of transforming growth factor-β(TGF-β),matrix metallopro-teinase-2(MMP-2)and CCN2 in shoulder joint capsule were detected by immunohistochemistry,the expressions of type I collagen(Collagen Ⅰ),type Ⅲ collagen(Collagen Ⅲ),ASK1,JNK,p-ASK1,and p-JNK in shoulder joint capsule were measured by Western blotting,the mRNA expressions of matrix metalloproteinase-1(MMP-1),tissue metalloprotein-ase inhibitor 1(TIMP1),type I collagen alpha 1(COL1A1)and type Ⅲ collagen alpha 1(COL3A1)in shoulder joint capsule were measured by Real-time quantitative PCR.Results Compared with the blank group,the levels of serum IL-1 and TNF-α were significantly increased in rats of the model group(both P<0.05);synovial cells were significantly prolif-erated,with localized infiltration of a large number of inflammatory cells and vascular hyperplasia;the average optical den-sity values of positive protein expressions of TGF-β,CCN2 and the relative protein expressions of Collagen Ⅰ,CollagenⅢ,ASK1,JNK,p-ASK1,p-JNK,and relative mRNA expressions of TIMP1,COL1A1,COL3A1 in shoulder joint cap-sule tissue were significantly increased(all P<0.05),while the average optical density value of positive protein expression of MMP-2 and relative mRNA expression of MMP-1 were significantly decreased(both P<0.05).Compared with the mod-el group,the levels of serum IL-1 and TNF-α were significantly decreased in rats of the low and high dose groups of decoc-tion for replenishing Qi and resolving stasis(all P<0.05);the proliferation of synovial cells was significantly decreased,with lighter infiltration of inflammatory cells and vascular hyperplasia;the average optical density values of positive protein expressions of TGF-β,CCN2 and the relative protein expressions of Collagen Ⅰ,Collagen Ⅲ,ASK1,JNK,p-ASK1,p-JNK,and relative mRNA expressions of TIMP1,COL1A1,COL3A1 in shoulder joint capsule tissue were significantly de-creased(all P<0.05),while the average optical density value of positive protein expression of MMP-2 and relative mRNA expression of MMP-1 were significantly increased(all P<0.05),the improvements of these indicators in the high dose group of decoction for replenishing Qi and resolving stasis were more significant than those in the low dose group(all P<0.05).Conclusion Decoction for replenishing Qi and resolving stasis can alleviate the inflammatory response and inhibit the fibrosis of shoulder joint capsule in rats with frozen shoulder rat model,the mechanism possibly is related to inhibiting the ASK1/JNK signaling pathway,thus to regulate expression of extracellular matrix collagen.关键词
益气化瘀方/冻结肩/关节囊/纤维化/凋亡信号调节激酶1/c-Jun氨基末端激酶Key words
decoction for replenishing Qi and resolving stasis/frozen shoulder/capsula articularis/fibrosis/apoptosis signal-regulating kinase1/c-Jun N-terminal kinase分类
医药卫生引用本文复制引用
陈柯村,曹彦俊,薄化君,徐丹丘,张璟婷,肖相如..基于ASK1/JNK信号通路探究益气化瘀方抑制冻结肩关节囊纤维化的机制[J].现代中西医结合杂志,2025,34(8):1035-1042,8.基金项目
上海市卫健委中医药科研项目(2022QN002) （2022QN002）
上海市虹口区第二轮"国医强优"三年行动计划项目(HK-GYQYXM-2022-27) （HK-GYQYXM-2022-27）
