| Obstructive sleep apnea hypopnea syndrome is a sleep respiratory disease characte-rized by chronic intermittent hypoxia.Clinically,it is often manifested as a series of symptoms such as irregular snoring,repeated suffocation,increased nocturia,daytime sleepiness,general fatigue,memory decline,etc.Osteoporosis is a systemic metabolic bone disease characterized by less bone mass and destruction of bone microstructure,resulting in increased bone brittleness and prone to fracture.The study found that OSAH patients caused a series of pathophysiological changes,such as hypoxia,CO2 retention,systemic inflammatory reaction,oxidative stress and so on,resulting in systemic and multi-system damage such as cardiovascular,nerve and endocrine,even closely related to the occurrence of lung cancer and other malignant tumors,which seriously affected the quality of life of patients.Some scholars have pointed out that OSAHS patients have the risk of osteoporosis,but specific mechanism of action is not clear.This study intends to explore the effects and possible mechanisms of OSAHS on bone metabolism furtherly from two aspects: sex hormone and OPG/RANKL system.Part 1.Study of the relationship between sex hormone and bone mineral density in male patients with OSAHSObjective To study the relationship of bone mineral density and sex hormone in male patients with OSAHS,and investigate the possible effects of sex hormones on OSAHS and osteoporosis.Methods According to the AHI,88 patients with OSAHS were collected and divided into three groups: mild(5?AHI<15times/h,n=30),moderate(15?AHI<30times/h,n=30)and severe(AHI?30times/h,n=28),30 non OSHAS persons as control.Recorded the general information,Measured the bone metabolic markers and bone mineral density of L1-4 and Neck,Determinated the expressions of serum sexhormone((E2,P,T,FSH,LH and PRL).At the same time,Comparated the difference in each group and analyzed the correlation with AHI,It had a significant difference by P<0.05.Results 1.Serum ALP?TPINP in severe OSAHS group were significantly lower than that in control group(P < 0.05);?-CTX in moderate and severe OSAHS group was significantly higher than that in control group and severe OSAHS group(P <0.05).2.The bone density of lumbar vertebrae and femoral neck in the moderate OSAHS group was significantly lower than that in the control group(P<0.05),and the lumbar vertebrae and femoral neck bone density in the severe OSAHS group were significantly lower than those in the control group and the mild OSAHS group(P<0.05).3.Serum testosterone levels in moderate and severe OSAHS group were significantly lower than those in the control group(P<0.05).4.The result of Pearson correlation analysis showed that testosterone was negatively correlated with AHI,bone mineral density of L1-4 and Neck was negatively correlated with AHI,testosterone was positively correlated with bone mineral density.Conclusion The risk of suffering from osteoporosis is higher in OSAHS patients and testosterone reduce in those people may be one of the reasons.Part 2.To study the effect of OSHAS on bone metabolism based on OPG/RANKL signaling pathway1.Changes of serum OPG,RANKL in OSAHS patientsObjective To study the changes of serum OPG,RANKL in OSAHS patientsMethods According to the AHI,88 patients with OSAHS were collected and divided into three groups: mild(5?AHI<15times/h,n=30),moderate(15?AHI<30times/h,n=30)and severe(AHI?30times/h,n=28),30 non OSHAS persons as control.Measured the expressions of serum OPG and RANKL by ELISA kits.At the same time,Comparated the difference in each group and analyzed the correlation with AHI,It had a significant difference by P<0.05.Results 1.Compared with the control group and the mild OSAHS group,the serum OPG in the severe OSAHS group was significantly lower(P < 0.05);the serum RANKL level in the moderate and severe OSAHS group was significantly higher(P <0.05),the serum RANKL level in the severe OSAHS group was also significantly higher than that in the mild OSAHS group(P < 0.05);the OPG / RANKL ratio in each group was significantly lower than that in the control group(P < 0.05).2.Pearson correlation analysis showed that serum OPG was negatively correlated with AHI(r =-0.296,P = 0.048),serum RANKL was positively correlated with AHI(r = 0.327,P = 0.012),and OPG/RANKL was negatively correlated with AHI(r =-0.531,P < 0.01).Conclusion The level of serum OPG and RANKL in OSAHS patients were decreased and increased,which were closely related to the degree of hypoxia.The imbalance of OPG and RANKL levels may be one of the main causes of the occurrence and development of OSAHS with osteoporosis.2.The effect of chronic intermittent hypoxia on bone metabolism and m RNA expression of OPG and RANKL in ratsObjective To investigate the effect of chronic intermittent hypoxia(CIH)on bone metabolism and OPG/RANKL pathway of bone tissue by Wistar rat.Methods Twenty adult healthy male Wistar rats were randomly divided into normal control group and CIH group with 10 rats in each group.The control group was placed in the air circulation cabin,and the CIH group was placed in the intermittent hypoxia cabin for 8 hours a day for 8 weeks.Bone mineral density(BMD)of the whole body,femur and lumbar vertebrae were measured by dual energy X-ray absorptiometry.The unilateral femur was stained with HE.Serum levels of BALP,BGP,PINP,CTX,TNF-?,IL-6,SOD and MDA were measured by ELISA.The relative expression of OPG and RANKL m RNA in femur tissue was measured by real time PCR,and the relative expression of OPG and RANKL protein was measured by Western blot.The difference between the two groups was statistically significant(P <0.05).Results 1.Compared with the control group,HE staining of the femur in the CIH group showed that the bone trabeculae were sparse,the space between the bone trabeculae increased significantly,some of the bone trabeculae were broken,a small amount of fibrous tissue proliferation was seen around,and inflammatory cell proliferation was found in the bone marrow.2.Compared with the control group,the serum BGP of CIH group decreased significantly(P < 0.05),while the serum ?-CTX and TRAP increased significantly(P< 0.05).3.Compared with the control group,the BMD of the whole body and femur in the CIH group decreased significantly(P < 0.05).4.Compared with the control group,the levels of TNF-?,IL-6,and MDA in CIH group were significantly higher(P < 0.05),and SOD is significantly lower(P < 0.05).5.Compared with the control group,the relative expression of OPG m RNA decreased,the relative expression of RANKL m RNA increased,and the ratio of OPG/ RANKL decreased in CIH group,they were significantly(P < 0.05).6.Compared with the control group,the expression level of OPG protein decreased and RANKL protein increased in the femur of the CIH group,they were significantly(P < 0.05).Conclusion Chronic intermittent hypoxia environment has inflammatory reaction and oxidative stress,which may affect bone metabolism,reduce bone density and increase the risk of osteoporosis through OPG/RANKL pathway.Part 3: The expression of LINC-PINT in bone tissue of rats under CIH environmentObjective To investigate the effect of CIH on the expression of LINC-PINT in bone tissue by establishing chronic intermittent hypoxia(CIH)model in Wistar rats.Methods 20 adult healthy male Wistar rats were randomly divided into normal control group and CIH group,10 rats in each group.The control group was placed in the air circulation cabin,and the CIH group was placed in the intermittent hypoxia cabin for 8 hours a day for 8 weeks.Real time PCR was used to detect the relative expression of LINC-PINT m RNA in femur,and the difference between the two groups was compared,and the correlation between LINC-PINT m RNA and bone mineral density was analyzed.P < 0.05 was statistically significant.Results 1.Compared with the control group,the relative expression of LINC-PINT m RNA in the femur of the CIH group were increased,the difference was statistically significant(P < 0.05).2.Pearson correlation analysis showed that LINC-PINT was negatively correlated with BMD in CIH group(r =-0.287,P = 0.043)Conclusion the up-regulation of linc-pint expression in bone tissue of rats under chronic intermittent hypoxia may be closely related to bone metabolism. |
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