Effect of Gubitongxiao granules in a mouse model of steroid-induced necrosis of the femoral head
- VernacularTitle:骨痹通消颗粒干预激素性股骨头坏死小鼠模型的作用及机制
- Author:
Xiang FANG
1
,
2
;
Zhengxin ZHOU
;
Lei ZHU
;
Ren RUI
;
Maoyu XU
;
Caiyu ZHU
Author Information
- Keywords: Gubitongxiao granule; Tongluo Shenggu capsule; steroid-induced necrosis of the femoral head; PTH1R; PKA; parathyroid hormone
- From: Chinese Journal of Tissue Engineering Research 2024;28(16):2599-2604
- CountryChina
- Language:Chinese
- Abstract: BACKGROUND:Glucocorticoids can inhibit the expression of hub genes in the parathyroid hormone type Ⅰ receptor(PTH1R)/protein kinase A(PKA)signaling axis and interfere with the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells,leading to the disruption of blood supply in bone and bone tissue structures.Previous studies of the research team showed that Gubitongxiao granules can induce blood vessel formation and inhibit osteoblast apoptosis,which has a certain effect on the prevention and treatment of steroid-induced femoral head necrosis. OBJECTIVE:To observe the therapeutic effect of Gubitongxiao granules in a mouse model of steroid-induced femoral head necrosis,and to explore its mechanism from the PTH1R/PKA signaling axis. METHODS:An animal model of steroid-induced necrosis of the femoral head was established by intraperitoneal injection of lipopolysaccharide and gluteal muscle injection of prednisolone acetate.After identification by nuclear magnetic resonance method,60 mice that were successfully modeled were divided into model group,Gubitongxiao granule group and Tongluo Shenggu capsule group,with 20 mice in each group.Another 12 normal mice were used as control group.The corresponding groups were intragastrically given the corresponding drugs for 12 weeks,and then the samples were taken under anesthesia.Histomorphology of femoral head samples was observed by hematoxylin-eosin staining.Enzyme-linked immunosorbent assay was used to detect the serum levels of bone alkaline phosphatase,type Ⅰ amino-terminal extension peptide,parathyroid hormone,osteocalcin and alkaline phosphatase.Western blot and RT-qPCR were used to detect PTH1R,PKA,myocyte enhancer factor 2,sclerostin and guanylate-binding protein activity-stimulating peptide at protein and gene expression levels,respectively. RESULTS AND CONCLUSION:Gubitongxiao granules may reduce the serum PTH level in mice,inhibit the activation of the PTH1R/PKA signal axis,further up-regulate the protein expressions of sclerostin and myocyte enhancer factor 2,and increase the levels of bone alkaline phosphatase,type Ⅰ amino-terminal extension peptide,osteocalcin and alkaline phosphatase in mice,thus improving femoral head necrosis,which is comparable to the intervention effect of Tongluo Shenggu capsules.It is speculated that Gubitongxiao granules may prevent and treating hormonal femoral head necrosis by regulating the PTH1R/PKA signaling axis.
