[1]董家赫,田勇,王孝辉,等.独活寄生汤调控软骨细胞氧化应激延缓大鼠膝骨关节炎软骨退变[J].中国中医骨伤科杂志,2024,32(05):9-13+17.[doi:10.20085/j.cnki.issn1005-0205.240502]
　DONG Jiahe,TIAN Yong,WANG Xiaohui,et al.Study of the Duhuo Jisheng Decoction in Delaying Cartilage Degeneration of Knee Osteoarthritis in Rats by Regulating the Chondrocyte Ferroptosis Activation Effect[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2024,32(05):9-13+17.[doi:10.20085/j.cnki.issn1005-0205.240502]
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独活寄生汤调控软骨细胞氧化应激延缓大鼠膝骨关节炎软骨退变()
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《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第32卷
期数:
2024年05期
页码:
9-13+17
栏目:
实验研究
出版日期:
2024-05-05

文章信息/Info

Title:
Study of the Duhuo Jisheng Decoction in Delaying Cartilage Degeneration of Knee Osteoarthritis in Rats by Regulating the Chondrocyte Ferroptosis Activation Effect
文章编号:
1005-0205(2024)05-0009-05
作者:
董家赫1; 田勇1; 王孝辉2; 谢艳2; 张海龙2; 尚万山2
1河南中医药大学(郑州,450046)
2河南省洛阳正骨医院
Author(s):
DONG Jiahe1; TIAN Yong1; WANG Xiaohui2; XIE Yan2; ZHANG Hailong2; SHANG Wanshan2
1Henan University of Chinese Medicine,Zhengzhou 450046,China; 2Luoyang Orthopedic-Traumatological Hospital of Henan Province,Luoyang 471002,Henan China.
关键词:
独活寄生汤;  骨关节炎;  氧化应激;  铁死亡
Keywords:
Duhuo Jisheng decoction;  osteoarthritis;  oxidative stress;  iron death
分类号:
R-33
DOI:
10.20085/j.cnki.issn1005-0205.240502
文献标志码:
A
摘要:
目的:观察独活寄生汤对外科手术诱导的膝骨关节炎(KOA)模型大鼠软骨细胞的保护作用并探讨其与软骨细胞氧化应激的关系。方法:将40只SPF级SD雌性大鼠随机分为空白组、模型组、实验组和对照组,每组各10只,除空白组大鼠外均采用改良的Hulth法制备膝骨关节炎模型,空白组以同样的方法打开关节腔不做任何处理,术后缝合关节腔。术后4周实验组给予中药独活寄生汤9.3 g/(kg·d)灌胃,空白组和模型组给予等量的生理盐水灌胃,对照组给予铁死亡抑制剂(Ferrostatin-1)2 mg/(kg·d)关节腔注射,连续用药12周。苏木精-伊红(HE)染色观察各组大鼠膝关节软骨组织形态并进行Mankin量化评分; 比色法检测各组大鼠血清中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH)含量; 蛋白免疫印迹法(Western Blot)检测各组大鼠膝关节软骨组织中上游信号抑癌基因(P53)、溶质载体家庭7成员11(SLC7A11)、谷胱甘肽过氧化酶4(GPX4)和基质金属蛋白酶13(MMP-13)蛋白表达。结果:与空白组比,模型组大鼠膝关节软骨病理损伤明显,Mankin评分升高,血清中MDA含量升高,差异有统计学意义(P<0.05); SOD和GSH含量降低,差异有统计学意义(P<0.05); 软骨组织中P53和MMP-13蛋白升高,差异有统计学意义(P<0.05); SLC7A11和GPX4蛋白降低,差异有统计学意义(P<0.05)。与模型组比,实验组和对照组大鼠膝关节软骨病理损伤改善,Mankin评分降低,血清中MDA含量降低,差异有统计学意义(P<0.05); SOD和GSH含量升高,差异有统计学意义(P<0.05); 软骨组织中P53和MMP-13蛋白降低,差异有统计学意义(P<0.05); SLC7A11和GPX4蛋白升高,差异有统计学意义(P<0.05)。结论:独活寄生汤可以通过调控软骨细胞氧化应激和细胞铁死亡对膝骨关节炎模型大鼠软骨产生保护作用,其机制可能是通过调控P53/SLC7A11/GPX4通路抑制软骨细胞凋亡,从而延缓膝骨关节炎的软骨退变。
Abstract:
Objective:To observe the protective effect of Duhuo Jisheng decoction on chondrocytes of surgically induced knee osteoarthritis(KOA)model rats and to explore its relationship with ferroptosis of chondrocytes.Methods:40 female SD rats with SPF grade were randomly divided into blank group,model group,experimental group and control group,with 10 rats in each group.Except for the blank group,the modified Hulth method was used to prepare the KOA model; the blank group opened the joint cavity without any treatment in the same way,and sutured the joint cavity after surgery.The experimental group received gavage of the traditional Chinese medicine Duhuo Jisheng decoction at a rate of 9.3 g/(kg·d),commencing from 4 weeks after the operation.The blank group and model group were both administered saline gavage at an equal amount,whereas the control group was given 2 mg/(kg·d)injection of the Ferrostatin-1 iron death inhibitor into the joint cavity for a duration of 12 weeks.Hematoxylin and eosin(HE)staining was utilized to observe the morphology of knee joint cartilage tissues of rats in each group.Mankin scoring system was utilized for quantitative assessment.Additionally,levels of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH)in the serum of rats in each group were determined using colorimetric assay.The levels of upstream signaling inhibitor(P53),solvent inhibitor,and oncogene(P53)in the cartilage tissues of the knee joints were analyzed by Western Blot in each group of rats.The protein expression of P53,solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4)and matrix metalloproteinase 13(MMP-13)in the same cartilage tissues was also detected using Western Blot.Results:Compared with the blank group,rats in the model group presented conspicuous pathological injury to their knee cartilage,and had a higher Mankin score,an elevated serum MDA level(P<0.05),reduced SOD and GSH levels(P<0.05),raised P53 and MMP-13 proteins in their cartilage tissue(P<0.05),and decreased SLC7A11 and GPX4 proteins(P<0.05).Compared with the model group,the pathological damage of knee cartilage in experimental group and control group was improved,the Mankin score was decreased; the contents of MDA in serum were decreased(P<0.05); the contents of SOD and GSH were increased(P<0.05); the proteins of P53 and MMP-13 in cartilage were decreased(P<0.05),and the proteins of SLC7A11 and GPX4 were increased(P<0.05).Conclusion:Duhuo Jisheng decoction can protect the cartilage of KOA model rats by regulating the ferroptosis of chondrocytes.The mechanism may be to inhibit the ferroptosis of chondrocytes by regulating the P53/SLC7A11/GPX4 signaling pathway,thus delaying the cartilage degeneration of KOA.

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更新日期/Last Update: 2024-05-15