To explore the molecular mechanism of kidney-tonifying and blood-activating method in the prevention and treatment of postmenopausal osteoporosis based on cAMP-PKA-CREB signaling pathway

Abstract

Purpose: Based on the cAMP-PKA-CREB signaling pathway, the possible intervention mechanism of kidney-nourishing and blood-activating decoction in the prevention and treatment of postmenopausal osteoporosis was discussed, providing new experimental evidence for elucidating the mechanism of kidney-nourishing and blood-activating decoction in the treatment of osteoporosis Methods: 60 healthy SD rats, female, 12 weeks old, body weight (240 + 20)g, were randomly divided and numbered after weighing. A total of 5 groups: blank control group (n=10), model group (n=10), western medicine group (n=10), high-dose Chinese medicine group (n=10) (16g/Kg. D), low-dose Chinese medicine group (n=10) (8g/Kg).For the blank control group and the model group, the western drug alendronate sodium group was given daily dose of alendrine sodium suspension for 8 weeks while the standard feed was routinely fed, and the dosage of intragastric drug was 10 mL/kg. For the group with high and low dose of traditional Chinese medicine, the standard feed was continued to be fed while the anti-sparing bone prescription concentrate was given daily for 8 weeks.In addition to the normal group and the model group, the animals in each group were collected at week 9 according to the corresponding dose of perfusion, and the bone mass was measured by double energy X-ray, and sacrificed the next day. The femoral head was taken for basic studies such as histomorphology and RT-PCR. Results: After 8 weeks in the model group, western medicine group, high-dose Chinese medicine group and low-dose Chinese medicine group, bilateral femoral head appeared obvious necrosis, while there was no obvious change in the normal group. Compared with the normal group, the expressions of cAMP and PKA in the model group, the western medicine group, the high-dose group and the low-dose group were all increased to different degrees, while the expression of CREB was significantly down-regulated. The expression of the above genes in the three groups was significantly different from that in the normal group (P<0.05). After 8 weeks of intragastric administration, the femoral head of the model group was dark and rough, resulting in osteoporosis. The femoral head of the high dose group and the low dose group showed no obvious change in appearance. In the western medicine group, the color of the femoral head was more bright, and some of the color was darker, but the morphology did not change significantly. In the morphology of femoral head of rats, the femoral head of rats in the western medicine group was lighter in color, but the morphology did not change significantly. Compared with the normal group, there was no significant difference in the expression of cAMP, PKA and CREB in the four groups of bone tissue (P>0.05). However, the expression of PKA and CREB was down-regulated in both the Chinese medicine group and the western medicine group, and the expression of cAMP was up-regulated, which was significantly different from the model group (P<0.05). Conclusions: By regulating the cAMP-PKA-CREB signaling pathway, kidney-invigorating and blood-activating formula can intervene in postmenopausal osteoporosis, inhibit the activity of osteoclasts, and activate osteoblasts, so as to cause normal metabolism of bone regeneration and bone remodeling, and delay the occurrence of osteoporosis.View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)