[1]郑世雄,林煜,刘合亮,等.基于PI3K/Akt通路探讨氟尿嘧啶对大鼠软骨细胞凋亡的影响[J].福建医药杂志,2024,46(03):99-103.[doi:10.20148/j.fmj.2024.03.031]
　ZHENG Shixiong,LIN Yu,LIU Heliang,et al.Effect of fluorouracil on chondrocyte apoptosis in rat based on PI3K/Akt signaling pathway[J].FUJIAN MEDICAL JOURNAL,2024,46(03):99-103.[doi:10.20148/j.fmj.2024.03.031]
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基于PI3K/Akt通路探讨氟尿嘧啶对大鼠软骨细胞凋亡的影响()
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《福建医药杂志》[ISSN:1002-2600/CN:35-1071/R]

卷:
46
期数:
2024年03期
页码:
99-103
栏目:
基础研究
出版日期:
2024-06-15

文章信息/Info

Title:
Effect of fluorouracil on chondrocyte apoptosis in rat based on PI3K/Akt signaling pathway
文章编号:
1002-2600(2024)03-0099-05
作者:
郑世雄; 林煜; 刘合亮; 魏艳珍
福建省福州市第二总医院创伤骨科,福州 350007
Author(s):
ZHENG Shixiong; LIN Yu; LIU Heliang; WEI Yanzhen
Department of Orthopedics,Fuzhou Second General Hospital,Fuzhou,Fujian 350007,China
关键词:
膝骨关节炎;  氟尿嘧啶;  细胞凋亡;  PI3K/Akt信号通路
Keywords:
knee osteoarthritis;  fluorouracil;  apoptosis;  PI3K/Akt signaling pathway
分类号:
R684.3; R-332
DOI:
10.20148/j.fmj.2024.03.031
文献标志码:
B
摘要:
目的 以PI3K/Akt信号通路为切入点,探讨氟尿嘧啶抑制膝骨关节炎模型大鼠软骨细胞凋亡的作用机制。方法 将36只雄性SD大鼠随机分为空白对照组、模型对照组和氟尿嘧啶治疗组,采用改良Hulth法制备膝骨关节炎模型,术后6周空白对照组和模型对照组于膝关节腔内注射生理盐水,氟尿嘧啶治疗组按2 mg/kg重组氟尿嘧啶注射液关节腔内注射,持续干预15 d后取材; 番红-固绿染色观察软骨组织结构变化,AB-PAS染色观察软骨基质黏蛋白分布变化,Real-time PCR和Western blot分别检测软骨组织PI3K、p-PI3K、Akt、p-Akt、Bcl-2和Bax mRNA和蛋白的表达水平。结果 模型对照组软骨4层结构紊乱,可见软骨缺失和软骨细胞凋亡,基质浅染甚至失染,酸性黏蛋白分布缩小和中性黏蛋白分布扩大,潮线不清; p-PI3K、p-Akt、Bcl-2 mRNA和蛋白表达水平均明显降低(P<0.01),Bax mRNA和蛋白表达明显升高(P<0.01)。与模型对照组相比,氟尿嘧啶治疗组软骨结构较规则,未见明显软骨缺失和细胞凋亡,基质染色较深,酸性黏蛋白分布扩大和中性黏蛋白分布缩小,潮线可见; p-PI3K、p-Akt、Bcl-2 mRNA和蛋白表达水平均明显升高(P<0.01),Bax mRNA和蛋白表达明显降低(P<0.01)。结论 关节腔内注射氟尿嘧啶可调控PI3K/Akt信号通路,抑制软骨细胞凋亡和基质降解,延缓关节软骨退变的病理进程。
Abstract:
Objective To explore the mechanism of fluorouracil inhibiting chondrocyte apoptosis in knee osteoarthritis rats based on PI3K/Akt signaling pathway.Methods Thirty six male SD rats were randomly divided into blank control group,model control group and fluorouracil group.Knee osteoarthritis model was established by modified Hulth's technique.Six weeks after surgery,the blank control group and the model control group were injected with physiological saline into the knee joint cavity,the fluorouracil treatment group were injected with 2 mg/kg fluorouracil into the knee joint cavity,for 15 days.The changes of cartilage tissue structure were observed by safranin-fast green staining.The distribution of cartilage matrix mucin was observed by AB-PAS staining.The expression levels of PI3K,p-PI3K,Akt, p-Akt,Bcl-2 and Bax mRNA and protein in cartilage tissue were detected by real-time PCR and western blot,respectively.Results In the model control group,the four layers of cartilage were disordered,cartilage loss and chondrocyte apoptosis were observed,the matrix was lightly stained or even lost,the distribution of acid mucin was reduced and the distribution of neutral mucin was expanded,and the tide line was unclear.The mRNA and protein expression levels of p-PI3K,p-Akt and Bcl-2 decreased significantly(P<0.01),and the mRNA and protein expression levels of Bax significantly increased(P<0.01).Compared with the model control group, in the fluorouracil treatment group the cartilage structure was more regular, no significant cartilage loss and apoptosis were observed,the matrix staining was deeper, the distribution of acidic mucin was expanded and the distribution of neutral mucin decreased,and the tidal line was visible.The mRNA and protein expression levels of p-PI3K,p-Akt and Bcl-2 significantly increased(P<0.01),while the mRNA and protein expression levels of Bax significantly decreased(P<0.01).Conclusion Intra articular injection of fluorouracil can regulate PI3K/Akt signal pathway,inhibit chondrocyte apoptosis and matrix degradation,and delay the pathological process of articular cartilage degeneration.

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备注/Memo

备注/Memo:
基金项目:福州市科技计划项目(2020-WS-68); 福建省创伤骨科急救与康复临床医学研究中心项目(2020Y2014)
通信作者:魏艳珍,Email:bear019@126.com
更新日期/Last Update: 2024-06-15