Hyperhomocysteinemia inhibits tibial fracture healing in rats through PI3K/AKT signaling pathway
| Autor: | Wei Zhang, Shoujing Tian, Yunzong Huang, Youjia Xu, Su Liu, Jianfei Ge |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
medicine.medical_specialty TUNEL assay Akt/PKB signaling pathway Chemistry Kinase Articles tibial fracture inflammatory response General Medicine Bone healing PI3K/AKT signaling pathway chemistry.chemical_compound Endocrinology Immunology and Microbiology (miscellaneous) Apoptosis Internal medicine medicine Phosphatidylinositol hyperhomocysteinemia Protein kinase B PI3K/AKT/mTOR pathway |
| Zdroj: | Experimental and Therapeutic Medicine |
| ISSN: | 1792-1015 1792-0981 |
| DOI: | 10.3892/etm.2020.8412 |
| Popis: | To explore the influence of hyperhomocysteinemia (hHcys) on the tibial fracture healing in rats and its effect on the phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (AKT) signaling pathway. A total of 36 Sprague-Dawley rats were randomly divided into sham group (n=12), tibial fracture group (n=12) and hHcys + fracture group (n=12). The rats in tibial fracture group underwent the tibial fracture surgery, while the model of tibial fracture and hHcys was established in hHcys + fracture group. The level of plasma homocysteine (Hcy) in each group was analyzed using the full-automatic biochemical analyzer, the fracture stress biomechanical measurement was performed, and the ultimate bending strength and torque were calculated. Moreover, the protein expressions of PI3K and phosphorylated (p)-AKT in tibial tissues were detected using western blotting, the messenger ribonucleic acid (mRNA) levels of Bcl-2 associated X protein (Bax) and caspase-3 were detected using quantitative polymerase chain reaction (qPCR), the apoptosis was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and the expressions of inflammatory factors were detected via immunohistochemistry. Compared with sham group, tibial fracture group and hHcys + fracture group had a significantly increased level of plasma Hcy, significantly decreased ultimate bending strength and torque, obviously decreased relative protein expressions of PI3K and p-AKT, increased mRNA levels of Bax and caspase-3 and an increased expression of pro-inflammatory factor tumor necrosis factor-α (TNF-α). Compared with tibial fracture group, hHcys + fracture group had a higher level of plasma Hcy, lower ultimate bending strength and torque, lower relative protein expressions of PI3K and p-AKT, higher mRNA levels of Bax and caspase-3, a higher apoptosis rate and a higher expression of TNF-α. hHcys blocks the downstream apoptotic signal transduction, promotes apoptosis and inflammatory response, and affects fracture healing through affecting the PI3K/AKT signaling pathway. |
| Databáze: | OpenAIRE |
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