摘要
目的探讨补肾活血方通过调控过氧化物酶体增殖物激活受体γ辅助激活因子1α(PGC-1α)信号通路对大鼠糖尿病性骨质疏松(DOP)的改善作用。方法将雄性SD大鼠分为对照组、模型组、二甲双胍组(100 mg/kg二甲双胍)、补肾活血方组(55 mg/kg补肾活血方)、补肾活血方+SR-18292组(55 mg/kg补肾活血方和45 mg/kg SR-18292)。除对照组外,其余各组采用高脂高糖饲料喂养联合链脲佐菌素腹腔注射进行DOP建模,造模成骨后各组给予相应药物干预。干预12周后,检测各组大鼠的股骨骨密度(BMD),空腹血葡萄糖(FBG)、空腹胰岛素(FIns)及骨钙素(OPG)、骨特异性碱性磷酸酶(BALP)、抗酒石酸酸性磷酸酶(TRAP),股骨生物力学指标最大载荷、刚度,股骨微结构指标骨小梁数(Tb.N)、骨小梁间隔(Tb.Sp)和骨小梁厚度(Tb.Th),股骨中p-AMPK、PGC-1α的蛋白表达水平。结果与对照组比较,模型组的股骨BMD、最大载荷、刚度、Tb.N、Tb.Th,血清OPG、BALP水平及股骨中p-AMPK、PGC-1α蛋白表达水平降低,血清FBG、FIns、TRAP水平及股骨Tb.Sp增加(P<0.05);与模型组比较,二甲双胍组及补肾活血方组的股骨BMD、最大载荷、刚度、Tb.N、Tb.Th,血清OPG、BALP水平及股骨中p-AMPK、PGC-1α蛋白表达水平增加,血清FBG、FIns、TRAP水平及股骨Tb.Sp降低(P<0.05);与补肾活血方组比较,补肾活血方+SR-18292组的股骨BMD、最大载荷、刚度、Tb.N、Tb.Th,血清OPG、BALP水平及股骨中p-AMPK、PGC-1α蛋白表达水平降低,血清FBG、FIns、TRAP水平及股骨Tb.Sp增加(P<0.05),p-AMPK蛋白表达水平无显著变化(P>0.05)。结论补肾活血方通过激活AMPK/PGC-1α通路改善大鼠DOP。
Objective To investigate the improving effect of Bushenhuoxue recipe on diabetic osteoporosis(DOP)rats by regulating the peroxi-some proliferator-activated receptor gamma co-activator 1α(PGC-1α)signaling pathway.Methods Male SD rats were divided into the control group,model group,metformin group(100 mg/kg metformin),Bushen Huoxue recipe group(55 mg/kg Bushen Huoxue recipe),and Bushen Huoxue recipe+SR-18292 group(55 mg/kg Bushen Huoxue recipe and 45 mg/kg SR-18292).In addition to the control group,the DOP model was established by high-fat and high-sugar diet feeding combined with intraperitoneal injection of streptozotocin,and the corresponding drug intervention was given to each group after osteogenic modeling.After 12 weeks of intervention,the femoral bone mineral density(BMD),fasting blood glucose(FBG),fasting insulin(FIns),osteocalcin(OPG),bone alkaline phosphatase(BALP),tartrate-resistant acid phosphatase(TRAP),femur biomechanical indexes maximum load and stiffness,bone microstructure index trabecular number(Tb.N),trabecular space(Tb.Sp)and trabecular thickness(Tb.Th),protein expression levels of p-AMPK and PGC-1αin femur were measured.Results Compared with the control group,the levels of BMD,OPG,BALP,maximum load,stiffness,Tb.N,Tb.Th,and the protein expression of p-AMPK and PGC-1αdecreased,while the levels of FBG,FIns,TRAP and Tb.Sp increased in model group(P<0.05).Compared with model group,the levels of BMD,OPG,BALP,maximum load,stiffness,Tb.N,Tb.Th,and the protein expression of p-AMPK and PGC-1αincreased,while the levels of FBG,FIns,TRAP and Tb.Sp decreased in metformin group and Bushen Huoxue recipe group(P<0.05).Compared with Bushen Huoxue recipe group,the levels of BMD,OPG,BALP,maximum load,stiffness,Tb.N,Tb.Th,and the protein expression of PGC-1αdecreased,while the levels of FBG,FIns,TRAP and Tb.Sp increased(P<0.05),while the protein expression of p-AMPK did not change significantly(P>0.05)in Bushen Huoxue recipe+SR-18292 group.Conclusion Bushen Huoxue recipe improves DOP of rats by activating AMPK/PGC-1αpathway.
作者
陈俊敏
兰佳明
黄珊
刘钰瑜
CHEN Junmin;LAN Jiaming;HUANG Shan;LIU Yuyu(Department of Pharmacy,Affiliated Hospital of Guangdong Medical University,Zhanjiang 524000,China;College of Marine and Tropical Medicine,Guangdong Medical University,Zhanjiang 524023,China;School of Pharmacy,Guangdong Medical University,Zhanjiang 524023,China)
出处
《安徽医学》
2025年第4期403-408,共6页
Anhui Medical Journal
基金
国家自然科学基金资助项目(编号:82274614)。
