Effect of fluorouracil on chondrocyte apoptosis in rat based on PI3K/Akt signaling pathway
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 cav-ity,the fluorouracil treatment group were injected with 2 mg/kg fluorouracil into the knee joint cavity,for 15 days.The chan-ges of cartilage tissue structure were observed by safranin-fast green staining.The distribution of cartilage matrix mucin was ob-served by AB-PAS staining.The expression levels of PI3K,p-PI3K,Akt,p-Akt,Bcl-2 and Bax mRNA and protein in carti-lage 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 un-clear.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 in-jection of fluorouracil can regulate PI3K/Akt signal pathway,inhibit chondrocyte apoptosis and matrix degradation,and delay the pathological process of articular cartilage degeneration.
万方数据
维普
