Effect of <italic style="font-style: italic">Xibining Formula</italic> （膝痹宁） on Knee Cartilage Tissue Damage and the cGAS-STING Signaling Pathway in  Knee Osteoarthritis Model Mice

FU Houyu; LI Xiaochen; GONG Zijian; JIE Lishi; LIU Jiangyu; CHEN Yingqi; WANG Peimin

doi:10.13288/j.11-2166/r.2025.12.011

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Effect of Xibining Formula （膝痹宁） on Knee Cartilage Tissue Damage and the cGAS-STING Signaling Pathway in Knee Osteoarthritis Model Mice

更新时间：2025-06-13

- Effect of Xibining Formula （膝痹宁） on Knee Cartilage Tissue Damage and the cGAS-STING Signaling Pathway in Knee Osteoarthritis Model Mice
- Journal of Traditional Chinese Medicine Vol. 66, Issue 12, Pages: 1257-1264(2025)
- 作者机构：
  
  1.南京中医药大学附属医院/江苏省中医院，江苏省南京市汉中路155号，210029
  2.南京中医药大学第一临床医学院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2025.12.011
  CLC：
- Received：27 February 2025，
  
  Revised：2025-03-25，
  
  Published：17 June 2025
- 稿件说明：
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伏厚宇,李晓辰,龚子健等.膝痹宁对膝骨关节炎模型小鼠膝关节软骨组织损伤及cGAS-STING信号通路的影响[J].中医杂志,2025,66(12):1257-1264.

FU Houyu,LI Xiaochen,GONG Zijian,et al.Effect of Xibining Formula （膝痹宁） on Knee Cartilage Tissue Damage and the cGAS-STING Signaling Pathway in Knee Osteoarthritis Model Mice[J].Journal of Traditional Chinese Medicine,2025,66(12):1257-1264.
伏厚宇,李晓辰,龚子健等.膝痹宁对膝骨关节炎模型小鼠膝关节软骨组织损伤及cGAS-STING信号通路的影响[J].中医杂志,2025,66(12):1257-1264. DOI： 10.13288/j.11-2166/r.2025.12.011.

FU Houyu,LI Xiaochen,GONG Zijian,et al.Effect of Xibining Formula （膝痹宁） on Knee Cartilage Tissue Damage and the cGAS-STING Signaling Pathway in Knee Osteoarthritis Model Mice[J].Journal of Traditional Chinese Medicine,2025,66(12):1257-1264. DOI： 10.13288/j.11-2166/r.2025.12.011.

摘要

目的

从环鸟苷酸-腺苷酸合成酶（cGAS）-干扰素基因刺激蛋白（STING）信号通路探讨膝痹宁治疗膝骨关节炎软骨损伤的可能作用机制。

方法

将50只C57BL/6J小鼠随机分为假手术组、模型组、膝痹宁低剂量组、膝痹宁高剂量组、膝痹宁高剂量+激动剂组，每组10只。除假手术组外，其余各组小鼠采用半月板失稳术构建膝骨关节炎小鼠模型。术后2周，膝痹宁低、高剂量组分别给予3.58、14.32 g/（kg·d）膝痹宁汤剂灌胃给药，膝痹宁高剂量+激动剂组使用14.32 g/（kg·d）膝痹宁汤剂灌胃后，按25 mg/kg腹腔注射2

5-己酮可可碱，假手术组与模型组给予5 ml/（kg·d）生理盐水灌胃，每日1次，各组均连续干预4周。采用ELISA法检测各组小鼠血清肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β）、白细胞介素6（IL-6）表达水平；苏木素-伊红、番红O-固绿染色观察软骨组织病理变化，并根据Mankin评分标准对病理变化进行评分；Western Blot法和qPCR法分别检测软骨组织基质调控相关指标［基质金属蛋白酶3（MMP3）、基质金属蛋白酶13（MMP13）、含血小板反应蛋白基序的解聚蛋白样金属蛋白酶5（ADAMTS5）、Ⅱ型胶原（COLⅡ）、聚集蛋白聚糖（Aggrecan）］水平及cGAS-STING通路相关指标（cGAS、STING）蛋白水平及mRNA表达。

结果

与假手术组比较，模型组小鼠软骨边缘破坏严重，Mankin评分升高，COLⅡ、Aggrecan蛋白及mRNA表达水平降低，cGAS、STING、MMP3、MMP13、ADAMTS5蛋白及mRNA表达水平升高（

＜0.01）；与模型组比较，各干预组小鼠血清IL-6、IL-1β、TNF-α水平均降低（

＜0.01）；与膝痹宁高剂量组比较，膝痹宁低剂量组及膝痹宁高剂量+激动剂组IL-6、IL-1β、TNF-α水平均升高（

＜0.01）。与模型组比较，膝痹宁低、高剂量组和膝痹宁高剂量+激动剂组小鼠软骨病理改变减轻，Mankin评分降低，COLⅡ、Aggrecan蛋白及mRNA表达水平升高，cGAS、STING、MMP3、MMP13、ADAMTS5蛋白及mRNA表达水平降低（

＜0.01）；与膝痹宁高剂量组比较，膝痹宁高剂量+激动剂组小鼠软骨边缘破坏，Mankin评分升高，COLⅡ、Aggrecan蛋白及mRNA表达水平降低，cGAS、STING、MMP3、MMP13、ADAMTS5蛋白及mRNA表达水平升高（

＜0.01）。

结论

膝痹宁可能通过抑制cGAS-STING通路，降低基质降解相关蛋白，升高基质组成相关蛋白，从而改善膝骨关节炎软骨损伤。

Abstract

Objective

To investigate the possible mechanism of action of

Xibining Formula

（膝痹宁） for cartilage damage in knee osteoarthritis （KOA） through the cyclic guanosine-adenosine monophosphate synthase （cGAS）- stimulator of interferon genes （STING） signaling pathway.

Methods

Fifty C57BL/6J mice were randomly divided into five groups （10 per group）， sham operation group， KOA model group， low-dose

Xibining Formula

group， high-dose

Xibining Formula

group， and high-dose

Xibining Formula

+ agonist group. The KOA models were constructed using the destabilization of the medial meniscus （DMM） method in all groups but the sham surgery group. Two weeks after surgery， the low- and high-dose

Xibining Formula

groups were administered

Xibining Formula

at doses of 3.58 g/（kg·d） and 14.32 g/（kg·d） respectively via gavage. The high-dose

Xibining Formula

+ agonist group received 14.32 g/（kg·d） of

Xibining Formula

via gavage followed by an intraperitoneal injection of Vadimezan （DMXAA） at 25 mg/kg. The sham surgery group and the KOA model group mice were given an equivalent volume of normal saline at 5 ml/（kg·d） via gavage， once daily for four consecutive weeks. Serum levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were measured by ELISA； pathological changes in cartilage tissue were observed using hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining. Pathological changes were scored according to the Mankin scoring system； the levels of cartilage tissue matrix regulation-related indicators such as matrix metalloproteinase 3 （MMP3）， matrix metalloproteinase 13 （MMP13）， a disintegrin and metalloproteinase with thrombospondin motifs 5 （ADAMTS）， type-Ⅱ collagen （CⅡ） and aggregated proteoglycan （Aggrecan）， and also cGAS-STING pathway-related protein and mRNA expression levels were detected by Western blot and qPCR methods.

Results

Compared with the sham surgery group， the KOA model group showed severe cartilage edge destruction， significantly increased Mankin scores， significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan， and significantly increased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （

＜0.01）. Compared with the control group， serum level of IL-6， IL-1β， TNF-α in all the intervented groups decreased （

＜0.01）， while compared with high-dose

Xibining Formula

group， level of IL-6， IL-1β， and TNF-α in low-dose

Xibining Formula

group and high-dose

Xibining Formula +

agonist

group increased （

＜0.01）. Compared with the KOA model group， all the intervention groups exhibited alleviated cartilage pathological changes， signi-ficantly reduced Mankin scores， s

ignificantly increased protein and mRNA expression levels of COLⅡ and Aggrecan， and significantly decreased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （

＜0.01）. Compared with high-dose

Xibining Formula

group， high-dose

Xibining Formula

+ agonist group showed cartilage edge destruction， significantly increased Mankin scores， significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan， and increased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （

＜0.01）.

Conclusion

Xibining Formula

may improve KOA cartilage damage by inhibiting the cGAS-STING signaling pathway， decreasing matrix degradation-related proteins， and elevating matrix composition-related proteins.

关键词

Keywords

references

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Effect of Xibining Formula （膝痹宁） on Knee Cartilage Tissue Damage and the cGAS-STING Signaling Pathway in Knee Osteoarthritis Model Mice

DOI：10.13288/j.11-2166/r.2025.12.011

摘要

Abstract

关键词

Keywords

references