Objective To investigate the effect of Fosinopril on ovariectomized tats and the effects of angiotensin system (RAS) and nitric oxide (NO) signaling pathway. Methods The rats were randomly divided into sham operation group,model group,fosinopril (high-dose group 10 mg/kg,medium-dose group 5 mg/kg,low-dose group 2.5 mg/kg) group,positive control group (captopril 40 mg/kg).Osteoporotic rat models were established by bilateral ovariectomy.Body weights were measured.Starting from the 8th week,rats in each group were given the corresponding drugs once a day for 6 consecutive weeks.The weigh of uterus and organ index was analyzed.The activity of TRACP,BALP and the content of calcium and phosphorus was detected by using standard colorimetry in rat serum.Micro-CT wasused to analyze the bone microstructure of the proximal femur of OVX rats and quantitative analysis of BMD,BV/TV,Tb.Th,Tb.Sp,Tb.N and BS/TV.The content of NO and NOS in rat serum was detected by using standard colorimetric method.The expression levels of AngⅡ,AT1R,ACE-1 and AT2R proteins in femoral tissue was analyzed by Western blot.Results Compared with the model group,Fosinopril significantly relieved the weight gain of OVX rats and increased the uterine organ index.Fosinopril treatment significantly reduced the TRACP and BALP activities in the serum of OVX rats,and increased the calcium and phosphorus levels in the serum.Fosinopril treatment also significantly improved bone microstructure damage in OVX rats,and alleviated the decrease in bone cortical thickness and bone mass,and significantly increased BV/TV,BS/TV,Tb.N,Tb.Th and BMD.Fosinopril treatment significantly increased the levels of NO and NOS in the serum of OVX rats,and down-regulated the expression of AngⅡ,AT1R,ACE1 protein and up-regulated the level of AT2R protein.Conclusion Fosinopril has potential therapeutic effect on osteoporosis,and it can improve bone metabolism and bone mineralization process and bone microstructure damage by regulating RAS/NO system signal.
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