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[1]鄭世雄,林煜,劉合亮,等.基于PI3K/Akt通路探討氟尿嘧啶對大鼠軟骨細(xì)胞凋亡的影響[J].福建醫(yī)藥雜志,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通路探討氟尿嘧啶對大鼠軟骨細(xì)胞凋亡的影響()
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《福建醫(yī)藥雜志》[ISSN:1002-2600/CN:35-1071/R]

卷:
46
期數(shù):
2024年03期
頁碼:
99-103
欄目:
基礎(chǔ)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
文章編號:
1002-2600(2024)03-0099-05
作者:
鄭世雄; 林煜; 劉合亮; 魏艷珍
福建省福州市第二總醫(yī)院創(chuàng)傷骨科,福州 350007
Author(s):
ZHENG Shixiong; LIN Yu; LIU Heliang; WEI Yanzhen
Department of Orthopedics,Fuzhou Second General Hospital,Fuzhou,Fujian 350007,China
關(guān)鍵詞:
膝骨關(guān)節(jié)炎;  氟尿嘧啶;  細(xì)胞凋亡;  PI3K/Akt信號通路
Keywords:
knee osteoarthritis;  fluorouracil;  apoptosis;  PI3K/Akt signaling pathway
分類號:
R684.3; R-332
DOI:
10.20148/j.fmj.2024.03.031
文獻(xiàn)標(biāo)志碼:
B
摘要:
目的 以PI3K/Akt信號通路為切入點,探討氟尿嘧啶抑制膝骨關(guān)節(jié)炎模型大鼠軟骨細(xì)胞凋亡的作用機(jī)制。方法 將36只雄性SD大鼠隨機(jī)分為空白對照組、模型對照組和氟尿嘧啶治療組,采用改良Hulth法制備膝骨關(guān)節(jié)炎模型,術(shù)后6周空白對照組和模型對照組于膝關(guān)節(jié)腔內(nèi)注射生理鹽水,氟尿嘧啶治療組按2 mg/kg重組氟尿嘧啶注射液關(guān)節(jié)腔內(nèi)注射,持續(xù)干預(yù)15 d后取材; 番紅-固綠染色觀察軟骨組織結(jié)構(gòu)變化,AB-PAS染色觀察軟骨基質(zhì)黏蛋白分布變化,Real-time PCR和Western blot分別檢測軟骨組織PI3K、p-PI3K、Akt、p-Akt、Bcl-2和Bax mRNA和蛋白的表達(dá)水平。結(jié)果 模型對照組軟骨4層結(jié)構(gòu)紊亂,可見軟骨缺失和軟骨細(xì)胞凋亡,基質(zhì)淺染甚至失染,酸性黏蛋白分布縮小和中性黏蛋白分布擴(kuò)大,潮線不清; p-PI3K、p-Akt、Bcl-2 mRNA和蛋白表達(dá)水平均明顯降低(P<0.01),Bax mRNA和蛋白表達(dá)明顯升高(P<0.01)。與模型對照組相比,氟尿嘧啶治療組軟骨結(jié)構(gòu)較規(guī)則,未見明顯軟骨缺失和細(xì)胞凋亡,基質(zhì)染色較深,酸性黏蛋白分布擴(kuò)大和中性黏蛋白分布縮小,潮線可見; p-PI3K、p-Akt、Bcl-2 mRNA和蛋白表達(dá)水平均明顯升高(P<0.01),Bax mRNA和蛋白表達(dá)明顯降低(P<0.01)。結(jié)論 關(guān)節(jié)腔內(nèi)注射氟尿嘧啶可調(diào)控PI3K/Akt信號通路,抑制軟骨細(xì)胞凋亡和基質(zhì)降解,延緩關(guān)節(jié)軟骨退變的病理進(jìn)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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備注/Memo

備注/Memo:
基金項目:福州市科技計劃項目(2020-WS-68); 福建省創(chuàng)傷骨科急救與康復(fù)臨床醫(yī)學(xué)研究中心項目(2020Y2014)
通信作者:魏艷珍,Email:[email protected]
更新日期/Last Update: 2024-06-15