摘要
目的探讨罗汉果皂苷Ⅵ对膝骨关节炎大鼠软骨损伤的影响及其作用机制。方法采用改良Hulth法制备大鼠膝骨关节炎模型,将大鼠随机分为模型组、硫酸氨基葡萄糖组(阳性对照,0.17 g/kg)、罗汉果皂苷Ⅵ低剂量组(27.5 mg/kg)和高剂量组(110 mg/kg),另设置假手术组,每组12只。各组给予相应药物灌胃干预,1次/d,连续8周。观察右侧膝关节肿胀程度;HE染色观察软骨组织病理学变化;ELISA检测软骨组织中IL-1β、IL-6、TNF-α和MMP-13表达水平;Western blot检测软骨组织中Cleaved-caspase-3、Bcl-2、Bax、p38MAPK、p-p38MAPK、MMP-13和NF-κB p65等蛋白表达水平。结果与假手术组比较,模型组右侧膝关节肿胀度显著增加(P<0.05),软骨组织损伤严重,软骨组织中IL-1β、IL-6、TNF-α和MMP-13水平及Cleavedcaspase-3、Bax、p-p38MAPK、MMP-13、NF-κB p65等蛋白表达水平显著升高(P<0.05),Bcl-2蛋白表达水平显著降低(P<0.05);与模型组比较,罗汉果皂苷Ⅵ高剂量组和阳性对照组右侧膝关节肿胀度显著降低(P<0.05),软骨组织损伤明显改善,软骨组织中IL-1β、IL-6、TNF-α和MMP-13水平及Cleaved-caspase-3、Bax、p-p38MAPK、MMP-13、NF-κB p65等蛋白表达水平显著降低(P<0.05),Bcl-2蛋白表达水平显著升高(P<0.05);罗汉果皂苷Ⅵ低剂量组各项检测指标与模型组比较无显著差异(P>0.05)。结论罗汉果皂苷Ⅵ可通过抑制软骨炎症反应和细胞凋亡,从而减轻膝骨关节炎软骨损伤,其机制可能与抑制p38MAPK信号通路活化有关。
To investigate the effects of mogrosideⅥon cartilage injury in rats with knee osteoarthritis and the mechanism.The knee osteoarthritis rats were prepared by an improved Hulth method,and then randomly divided into model group,glucosamine sulfate group(positive control,0.17 g/kg),mogrosideⅥlow-dose group(27.5 mg/kg)and high-dose group(110 mg/kg),with 12 in each group,and another 12 rats were recruited as sham operation group.Rats in each group were given relevant drug intragastric intervention,once a day,for consecutive 8 weeks.The swelling degree of the right knee joint was observed;HE staining was used to detect the histopathological changes of cartilage;ELISA was used to detect the expression levels of IL-1β,IL-6,TNF-αand MMP-13 in cartilage tissues;Western blot was used to detect the protein expression levels of Cleaved caspase-3,Bcl-2,Bax,p38MAPK,p-p38MAPK,MMP-13 and NF-κB p65 in cartilage tissues.Compared with the sham operation group,the swelling degree of right knee joint in model group was significantly increased(P<0.05),the cartilage was severely damaged,the levels of IL-1β,IL-6,TNF-αand MMP-13 and the protein expression levels of Cleaved caspase-3,Bax,p-p38MAPK,MMP-13 and NF-κB p65 in cartilage tissues were significantly increased(P<0.05),the protein expression level of Bcl-2 was significantly decreased(P<0.05).Compared with the model group,the indexes mentioned above were all reversed in the mogrosideⅥhigh-dose group and the positive control group(P<0.05).While there were no significant differences in the detection indexes between the mogrosideⅥlow-dose group and the model group(P>0.05).In conclusion,mogrosideⅥcan alleviate cartilage injury in knee osteoarthritis by inhibiting cartilage inflammation and cell apoptosis,and the mechanism may relate to the inhibiting of p38MAPK signaling pathway activation.
作者
曾智
李浩
王晓旭
杨俊涛
ZENG Zhi;LI Hao;WANG Xiaoxu;YANG Juntao(Department of Joint Surgery,Second Affiliated Hospital,Hengyang Medical School,University of South China,Hengyang 421001,China;Department of Hand and Foot Surgery,Second Affiliated Hospital,Hengyang Medical School,University of South China,Hengyang 421001,China)
出处
《免疫学杂志》
CAS
CSCD
北大核心
2022年第9期804-809,共6页
Immunological Journal
基金
湖南省卫生健康委2019年度科研计划课题项目(C2019103)。