关键词: 骨坚散, 激素性股骨头坏死, 脂代谢, 成骨障碍, PPARγ, 信号通路

Abstract:

Objective To explore the effects of Gujiansan on bone and lipid metabolism in rat models of steroid-induced necrosis of the femoral head. Methods The rats were divided into the control group， the model group， and the low-dose， medium-dose， and high-dose groups of Gujiansan， with 10 rats in each group. Except for the control group， lipopolysaccharide and glucocorticoid were administered to the other groups to establish the steroid-induced necrosis of the femoral head model. The low-dose， medium-dose， and high-dose Gujiansan groups were respectively given 1.05， 2.10， and 4.20 g/kg of Gujiansan via gavage daily. Eight weeks later， the contents of low-density lipoprotein cholesterol （LDL-C）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and triglycerides （TG） were measured. RT-qPCR and Western blot were employed to detect the relative mRNA and protein expression levels of peroxisome proliferator-activated receptor γ （PPARγ）， CCAAT enhancer binding protein α （C/EBPα）， CCAAT enhancer binding protein β （C/EBPβ）， Runt-related transcription factor 2 （Runx2）， osteopontin （OPN）， and alkaline phosphatase （ALP） in femoral head tissues. Micro-CT was utilized to observe the alterations in the bone mass of the rat femoral head； Hematoxylin-eosin （HE） staining was used to observe the pathological morphological changes of the femoral head tissue. Immunohistochemistry （IHC） was applied to observe the protein expressions of osteocalcin （OCN） and Runx2 in the femoral head. Results Compared with the model group， after treatment with Gujiansan， the contents of serum TC， TG， and LDL-C decreased （P < 0.05）， whereas the content of HDL-C increased （P < 0.05）. Additionally， the mRNA and protein expression levels of peroxisome PPARγ， C/EBPα， and C/EBPβ decreased （P < 0.05）， while those of Runx2， ALP， and OPN increased （P < 0.05）. Moreover， the bone volume fraction， trabecular thickness， trabecular number， trabecular connection density， and bone mineral content increased （P < 0.05）， the trabecular separation degree decreased （P < 0.05）， the rate of empty bone pits in the femoral head tissue decreased （P < 0.05）， and the expression levels of OCN and Runx2 proteins increased （P < 0.05）. Conclusion This study shows that the low-dose， medium and high-dose groups of Gujiansan all have the effect of regulating the homeostasis of bone lipid metabolism， and the high-dose group of Gujiansan has the most significant effect； Gujiansan may improve lipid metabolism disorders in rats with steroid-induced necrosis of the femoral head via the PPARγ signaling pathway， promote osteogenic differentiation， restore the balance of bone-lipid metabolism， and consequently promote the repair of osteonecrosis.

Key words: Gujiansan, steroid-induced necrosis of the femoral head, lipid metabolism, osteogenic disorder, PPARγ, signal path