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ObjectiveTo investigate the effect of Jingui Shenqiwan on diabetic osteoporosis （DOP） in mice by regulating the advanced glycation end products （AGEs）/receptor activator of nuclear factor-κB ligand （RANKL）/nuclear factor-κB （NF-κB） signaling pathway based on the theory of "kidneys governing bones". MethodForty 6-week-old male and female skeletal-muscle-specific， dominant negative insulin-like growth factor-1 receptor （MKR） mice were selected and fed on a high-fat diet for eight weeks to establish the DOP model. The model mice were randomly divided into a model group， low- and high-dose Jingui Shenqiwan group （1.3， 2.6 g·kg-1）， and an alendronate sodium group （0.01 g·kg-1）， with 10 mice in each group. Additionally， 10 FVB/N mice of the same age were assigned to the normal group. The corresponding drugs were administered orally to each group once a day for four weeks. After the administration period， fasting blood glucose （FBG） measurement and oral glucose tolerance test （OGTT） were conducted. Kidney function and kidney index were measured. Renal tissue pathological changes were observed through hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry was performed to assess the protein expression levels of AGEs， phosphorylated NF-κB （p-NF-κB）， and RANKL in renal tissues. Western blot analysis was conducted to measure the expression of proteins related to the AGEs/RANKL/NF-κB signaling pathway， osteoprotegerin （OPG）， and Runt-related transcription factor 2 （RUNX2） proteins in femoral bone tissues. ResultCompared with the normal group， mice in the model group exhibited significantly increased FBG （P<0.01）， trabecular bone degeneration， abnormal bone morphological parameters， significantly increased area under the curve （AUC） of OGTT （P<0.01）， enlarged kidney volume， significantly increased kidney function indicators and kidney index （P<0.01）， disrupted renal glomeruli and renal tubule structures， significantly increased expression of AGEs， RANKL， and p-NF-κB/NF-κB in renal tissues （P<0.05）， and significantly decreased expression of OPG and RUNX2 in femoral bone tissues （P<0.01）. Compared with the model group， mice in the Jingui Shenqiwan groups showed a significant decrease in OGTT AUC （P<0.01）. Histopathological analysis revealed alleviated structural lesions in renal glomeruli and renal tubules. Furthermore， the expression of AGEs， RANKL， and p-NF-κB/NF-κB in renal tissues was significantly reduced （P<0.05， P<0.01）， and the expression of RUNX2 and OPG in femoral bone tissues was significantly increased （P<0.05， P<0.01）. ConclusionJingui Shenqiwan can improve kidney function and downregulate the AGEs/RANKL/NF-κB signaling pathway to inhibit inflammatory reactions， thereby alleviating the symptoms of DOP in mice， demonstrating a therapeutic effect on DOP from the perspective of the kidney.
RESUMEN
Objective:To evaluate the short-term and long-term efficacy of Jingui Shenqiwan combined with three-stage syndrome differentiation on osteoporotic vertebral compression fractures (OVCFs) after operation, and its regulatory effect on biomarkers of bone metabolism. Method:One hundred and thirty-five patients were randomly divided into control group (67 cases) and observation group (68 cases) by random number table. A total of 58 patients in control group completed the treatment (4 patients were exfoliated, 2 patients were lost to follow-up, 3 patients were eliminated); and 60 patients in observation group completed the treatment (3 patients were exfoliated, 2 patients were lost to follow-up, 3 patients were eliminated). Both groups patients were given calcitonin injection through intramuscular injection, 20 u/time, 1 time/week, for 12 weeks, calcium carbonate D3 chewable tablets (Ⅱ), 1 tablet/time, 2 times/day, and alendronate sodium tablets, 70 mg/time, 1 time/week. Patients in control group got Bushen Jiangu capsule, 4 grains/time, 3 times/day. And patients in observation group got modified Jingui Shenqiwan combined with fracture three-stage symptom differentiation, 1 dose/day. The courses of treatment in the two groups were 24 weeks, and a 24 week follow-up was provided. Before the operation and at the 12th and 24th week after operation, the short-term efficacy indexes, such as back pain, lumbar function, traditional Chinese medicine （TCM） syndromes and complications, were recorded. And the long-term efficacy indexes, such as recovery of responsible vertebral body, lumbar function, bone density and quality of life and incidence of 48 week re-fracture, were also recorded. Before and after operation, levels of bone alkaline phosphatase (BALP), osteocalcin (BGP), tartrate resistant acid phosphatase-5b (TRAP-5b), type I collagen carboxy terminal prepeptide (PICP), type I collagen cross-linked C-terminal peptide (β-CTX) and N-MID-OT were detected, and the safety was evaluated. Result:The comprehensive efficacy in observation group was superior to that in control group (Z=2.026, P<0.05). At the 12th and 24th week after operation, scores of back pain, lumbar function and TCM syndromes were all lower than those in control group (P<0.01), and score of lumbar function at the 48th week after operation was also lower than that in control group (P<0.01). Bone density was higher than that in control group at the 24th and 48th week after operation, and score of quality of life was lower than that in control group (P<0.01). At the 24th and 48th week after operation, Cobb angles were less than those in control group, and heights of responsible centrums (anterior, central, posterior) were higher than those in control group. Cumulative incidence of complications in control group was 51.72% (30/58), which was higher than 26.67% (16/60) in control group (χ2=7.784, P<0.01). The levels of BGP were higher than those in observation group at the 24th and 48th week after operation, and the levels of BALP, TRAP-5b, PICP, β-CTX and N-MID-OT were all lower than those in control group (P<0.01). And there was no side effect relating to Jingui Shenqiwan. Conclusion:Modified Jingui Shenqiwan combined with fracture three-stage symptom differentiation can reduce the symptoms of back pain and promote the recovery of lumbar function, with a significant short-term comprehensive efficacy. In the long term, it can improve the strength of responsible centrums, restore the anatomical structure of injured centrums, increase the bone density of centrums, further improve the lumbar function, reduce the occurrence of complications, regulate the markers of bone metabolism, and improve osteoporosis.