【目的】 观察杜鹃花总黄酮对骨关节炎大鼠软骨组织损伤的改善作用及其潜在作用机制。【方法】 将Wistar大鼠随机分为 模型组，塞来昔布组，杜鹃花总黄酮低、中、高剂量组和假手术组。除假手术组外，其他各组大鼠以单次膝关节内注射单 碘乙酸酯（MIA）构建骨关节炎模型。分组干预后，测量膝关节宽度和被动活动度，采用苏木精-伊红（HE）染色法观察软骨组 织病理形态，并进行Mankin’s评分，原位末端标记法（TUNEL）检测软骨组织细胞凋亡，蛋白免疫印迹（Western Blot）法检测 软骨组织损伤相关蛋白胶原蛋白Ⅱ（collagen Ⅱ）、聚集蛋白聚糖（aggrecan）、基质金属蛋白酶（MMP）-9和MMP-13及NOD样 受体家族 Pyrin 结构域 3（NLRP3）/半胱氨酸蛋白酶 1（caspase-1）通路蛋白 NLRP3、凋亡相关斑点样蛋白（ASC）和剪切的 caspase-1（cleaved caspase-1）的表达，比色法检测软骨组织caspase-1活性，酶联免疫吸附分析（ELISA）检测血清白细胞介素 （IL）-6、肿瘤坏死因子α（TNF-α）、IL-18、IL-1β水平。【结果】 与假手术组比较，模型组大鼠膝关节软骨组织出现明显损伤， 膝关节宽度、Mankin’s 评分，软骨组织 caspase-1 活性，TUNEL 染色凋亡软骨细胞比例，软骨组织 MMP-9、MMP-13、 NLRP3、ASC和cleaved caspase-1蛋白表达水平，血清IL-6、TNF-α、IL-1β和IL-18水平均显著升高，膝关节被动活动度， 软骨组织collagen Ⅱ和aggrecan蛋白表达水平显著降低，差异均有统计学意义（P＜0.05）。与模型组比较，杜鹃花总黄酮中、 高剂量组和塞来昔布组大鼠膝关节软骨组织损伤减轻，膝关节宽度、Mankin’s评分，软骨组织caspase-1活性，TUNEL染色 凋亡软骨细胞比例，软骨组织 MMP-9、MMP-13、NLRP3、ASC 和 cleaved caspase-1 蛋白表达水平，血清 IL-6、TNF-α、 IL-1β和IL-18水平均显著降低，膝关节被动活动度，软骨组织 collagen Ⅱ和 aggrecan 蛋白表达水平均显著升高，差异均有 统计学意义（P＜0.05）。【结论】 杜鹃花总黄酮可改善骨关节炎大鼠软骨损伤，其机制可能与抑制NLRP3/caspase-1通路介导 的细胞焦亡有关。

Objective To observe the improvement effect of total flavonoids from Rhododendron （TFR） on cartilage tissue injury in osteoarthritis rats and its potential mechanism. Methods Wistar rats were randomly divided into the model group，Celecoxib group，TFR low-，medium- and high-dose group，and sham-operated group. Except for the sham-operated group，osteoarthritis models were established in all other groups by a single intra-articular injection of monosodium iodoacetate （MIA）. After grouped interventions，the knee joint width and passive range of motion were measured；histopathological morphology of cartilage tissue was observed by hematoxylin-eosin （HE） staining with Mankin’s scoring；apoptosis in cartilage tissue was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling（TUNEL） assay；protein expression levels of cartilage damage-related proteins collagen Ⅱ，aggrecan，matrix metalloproteinase（MMP）-9，MMP-13，and NLRP3/caspase-1 pathway proteins NLRP3， apoptosis-associated speck-like protein（ASC），and cleaved caspase-1 were analyzed by Western Blot；caspase- 1 activity in cartilage tissue was measured by colorimetric assay；and serum levels of interleukin （IL）-6，tumor necrosis factor α（TNF-α），IL-18，and IL-1α were detected by enzyme-linked immunosorbent assay（ELISA）. Results Compared with the sham-operated group，the model group exhibited significant cartilage damage，with markedly increased knee joint width， Mankin’s score， caspase-1 activity in cartilage tissue， proportion of TUNEL-positive apoptotic chondrocytes，protein expression levels of MMP-9，MMP-13，NLRP3，ASC，and cleaved caspase-1 in cartilage tissue，and serum levels of IL-6，TNF-α，IL-1β，and IL-18（all P＜0.05）. Meanwhile，the passive range of motion and protein expression levels of collagen Ⅱand aggrecan in cartilage tissue were significantly reduced （all P＜0.05）. Compared with the model group， the TFR medium- and high-dose group， and Celecoxib group showed alleviated cartilage damage， along with significantly decreased knee joint width， Mankin’s score， caspase-1 activity， proportion of TUNEL-positive apoptotic chondrocytes， protein expression levels of MMP-9， MMP-13， NLRP3， ASC， cleaved caspase-1， and serum IL-6， TNF- α， IL-1β，and IL-18 levels （all P＜0.05）. Additionally，the passive range of motion and protein expression levels of collagen Ⅱ and aggrecan were significantly increased （all P＜0.05）. Conclusion TFR can improve cartilage damage in osteoarthritic rats， and its mechanism may be associated with the inhibition of NLRP3/caspase-1 pathway-mediated pyroptosis.

R285.5

河北省重点研发计划项目（编号：22032812376D）