| Diabetic osteoporosis refers to a systemic metabolic bone disease in which diabetes is accompanied by bone mass decrease,the microstructure of bone tissue damage,bone fragility increasing,and easy to fractures.It is a serious chronic complication caused by diabetes in the skeletal system,with high incidence and disability,which seriously affects the quality of life of patients.The pathogenesis of diabetic osteoporosis is complex.Current studies have shown that under the stimulation of chronic inflammation,the activity of 11 ?-hydroxysteroid dehydrogenase type 1(1 1?-HSD1)in local target organs and tissues such as liver and adipose tissue increases.The process of converting inactive 11 dehydrocorticosterone into active corticosterone has increased,which is an important pathophysiological process of diabetic osteoporosis.At present,there is still a lack of specific medicine with long-lasting effects,small side effects.Traditional Chinese medicine has unique advantages in the prevention and treatment of diabetic osteoporosis,with rich targets,few adverse reactions,and definite curative effects,and it is widely used in clinical practice.This paper analyzes the TCM syndromes and clinical characteristics of type 2 diabetes with osteoporosis through clinical research;through animal experiment research,explores the effect of puerarin on the prevention and treatment of osteoporosis in diabetic rats;taking anti-inflammatory and inhibiting 11?-HSD1 activity as the starting point to explore the mechanism of puerarin's intervention in diabetic osteoporosis;provide new ideas and methods for the clinical prevention and treatment of diabetic osteoporosis.1.Clinical researchObjective:To collect case data of type 2 diabetes inpatients,analyze the TCM syndromes and clinical characteristics of type 2 diabetes with osteoporosis,and provide a certain basis for the clinical prevention and treatment of type 2 diabetes with osteoporosis.Methods:The data of 96 patients with type 2 diabetes who were hospitalized from October 2018 to October 2020 in the Department of Endocrinology,Dongfang Hospital Beijing University of Chinese Medicine were collected.According to bone mineral density,the patients were divided into T2DM group(45 cases)with normal bone mass and Combined Osteoporosis Group(51 cases)with osteoporosis.Explore the characteristics of TCM syndromes of the two groups of patients,and analyze gender,age,diabetes course,HbA1C,Ca,P,ALP,25(OH)VD.PTH.osteocalcin,T-P1NP,?-CTX,bone mineral density and other related indicators to provide a theoretical basis for the effective prevention and treatment of type 2 diabetes with osteoporosis.Results:?The ratio of the main syndrome types of the two groups of patients,T2DM group Qi and Yin deficiency syndrome>Lung and stomach heat syndrome>Yin deficiency and fire strong syndrome,Combined Osteoporosis Group Qi and Yin deficiency syndrome>Yin deficiency and fire prosperity syndrome>Lung and stomach heat syndrome.The distribution of the main syndrome types of the two groups is different,with significant differences(P<0.05);the two groups of concurrent syndromes are blood stasis blocking collateral syndrome>phlegm-dampness internal accumulation syndrome,there is a significant difference(P<0.05);There was no significant difference in bone mineral density(P>0.05)of the three the main syndrome of Combined Osteoporosis Group.? The gender distribution of the two groups of patients is different.There are more male patients in the T2DM group and more female patients in the Combined Osteoporosis Group,with significant differences(P<0.05).?The age distribution of the two groups of patients is different.The age of the patients in the Combined Osteoporosis Group is higher than that in the T2DM group,which is significantly different(P<0.05).?The course of diabetes was different between the two groups.The course of diabetes in the DOP group was longer than that in the T2DM group,which was significantly different(P<0.05).?There was no significant difference in the levels of glycosylated hemoglobin between the two groups(P>0.05).? There was no significant difference in blood Ca,blood P,25(OH)VD,PTH,and ?-CTX levels between the two groups of patients(P>0.05);the levels of ALP and T-P1NP were different,and the levels of ALP and T-P1NP in the Combined Osteoporosis Group were higher than those in T2DM There was a significant difference between the two groups(P<0.05);the level of osteocalcin was different,and the level of osteocalcin in the Combined Osteoporosis Group was lower than that in the T2DM group,with a significant difference(P<0.05).Conclusion:?The syndrome of deficiency of both Qi and Yin is the most main syndrome,and the syndrome of blood stasis obstructing the collaterals is the most concurrent syndrome of type 2 diabetes combined with osteoporosis;the main syndrome of Yin deficiency and fire vigor is significantly higher than the T2DM group.It provides certain ideas for the prevention and treatment of type 2 diabetes with osteoporosis in clinical Chinese medicine.?Type 2 diabetes with osteoporosis is closely related to gender,age,and course of diabetes.?Patients with type 2 diabetes and osteoporosis have higher blood ALP and T-P1NP levels,and lower osteocalcin levels.It provides a certain basis for early detection,effective prevention and treatment of osteoporosis in clinic.2.Animal experimentObjective:To use puerarin to intervene in type 2 diabetic rats,with anti-inflammation and inhibition of 11?-HSD1 activity as targets,to explore the effect and mechanism of puerarin on improving osteoporosis in diabetic rats.Methods:?Establish type 2 diabetes rat model,and intervene with different doses of puerarin.Biochemical methods,enzyme-linked immunoassay(ELISA)and related instruments are used to detect blood glucose,insulin,and bone metabolism related indicators(blood calcium,25 hydroxyl).Vitamin D,TRACP5b,CTX-1,ALP-B,OC,bone density),to explore the prevention and treatment effect of puerarin on osteoporosis in diabetic rats.(2)Enzyme-linked immunosorbent assay(ELISA)was used to measure inflammation-related cytokines and corticosterone metabolism-related indicators:MCP-1,TNNF-?,IL-1,IL-6,hs-CRP and the active form of serum glucocorticoid corticosterone,which is closely related to inflammatory reactions;by RT-PCR and Western blot methods,the gene,protein expression and enzyme activity of 11?-HSD1 in rat liver,fat,and bone tissues were detected to clarify the inflammatory response and 11? of puerarin-The influence of HSD1 activity to clarify the target and mechanism of puerarin.Results:?In terms of glucose metabolism,the blood glucose of rats in the three groups of puerarin(low,medium,and high dose)was significantly lower than that of the model group(P<0.05),and the blood glucose level of the high dose group was the lowest(P<0.05);The insulin level of rats in the three treatment groups was significantly higher than that in the model group(P<0.05),and the level of insulin in the middle dose group was the highest(P<0.05).?In terms of bone metabolism,the blood calcium and 25(OH)VD of rats in the three treatment groups of puerarin were significantly increased compared with the model group(P<0.05),and the blood calcium and 25(OH)VD levels of the high dose group were the highest(P<0.05);Serum TRACP5b,CTX-1,and ALP-B in the three groups of Puerarin were significantly lower than those in the model group P<0.05),and the serum TRACP5b,CTX-1,and ALP-B levels in the middle agent group were the lowest(P<0.05);The serum OC of rats in the three groups of puerarin was significantly higher than that of the model group(P<0.05).Among them,the serum OC level of the middle agent group was the highest(P<0.05);The bone mineral density of the three groups of puerarin increased compared with the model group(P<0.05);there was no statistical difference between the three groups(P>0.05).?Inflammation indicators:MCP-1,TNF-?,IL-1,and hs-CRP in the three groups of puerarin were significantly decreased compared with the model group(P<0.05).Among them,MCP-1,TNF-?,IL-1,hs-CRP level in the medium group was the lowest(P<0.05).?In terms of corticosterone metabolism,the serum corticosterone concentration of rats in the three groups of puerarin decreased significantly compared with the model group(P<0.05),among which the concentration of corticosterone in the middle dose group was the lowest(P<0.05);The expression of 11?-HSD1 protein and mRNA in liver,fat,bone and bone tissues of rats in the three groups of puerarin decreased compared with the model group(P<0.05).Among them,the expression of 11?-HSD1 protein and mRNA in the middle agent group was the lowest(P<0.05).Conclusion:?In terms of glucose metabolism and bone metabolism,puerarin can reduce blood sugar and increase insulin levels;puerarin can increase blood calcium,25(OH)VD,OC and bone density,and reduce TRACP5b,CTX-1,ALP-B's role.It shows that puerarin can regulate blood glucose,insulin,calcium,25(OH)VD metabolism,inhibit bone resorption,promote bone formation,regulate bone transformation,and improve osteoporosis in diabetic rats.?In terms of inflammation and corticosterone metabolism,puerarin can reduce the levels of MCP-1,TNF-?,IL-1,hs-CRP,and corticosterone,and reduce the activity of 11 ?-HSD1 in liver,fat,and bone tissues;It shows that puerarin may reduce the activation of corticosterone by anti-inflammatory and inhibit the activity of 11?-HSD1,and achieve the effect of improving osteoporosis in diabetic rats.?Comparing different doses of puerarin,the middle dose group has the best effect in increasing insulin levels,regulating bone metabolism,anti-inflammatory and inhibiting 11?-HSD1 activity. |
PDF Full Text Request