机构地区:[1]新疆医科大学药学院,乌鲁木齐830017 [2]新疆维吾尔自治区药物研究所,乌鲁木齐830004 [3]和田维吾尔药业股份有限公司,新疆和田848200 [4]中国医学科学院药物研究所,北京100050
出 处:《新疆医科大学学报》2024年第6期877-882,共6页Journal of Xinjiang Medical University
基 金:新疆维吾尔自治区自然科学基金青年基金项目(2022D01F115);新疆维吾尔自治区“十四五”重大专项项目(2022A03017)。
摘 要:目的研究罗补甫克比日丸对更年期大鼠激素分泌和骨代谢的影响。方法取6只2月龄正常大鼠为正常对照组(0.5%CMC-Na),通过观察阴道涂片筛选出30只发情周期紊乱的12月龄自然衰老大鼠为更年期模型,将更年期模型大鼠随机分为5组:模型组(0.5%CMC-Na),低剂量组(罗补甫克比日丸,236 mg/kg体重),中剂量组(罗补甫克比日丸,472 mg/kg体重),高剂量组(罗补甫克比日丸,945 mg/kg体重),更年安组(更年安片,585 mg/kg体重),每组6只,每天灌胃1次,连续30 d。观察并记录给药期间各组大鼠的体重变化,采用试剂盒检测各组大鼠血清中雌二醇(Estradiol,E2)、促卵泡生成素(Follicle-stimulating hormone,FSH)、促黄体生成素(Lute-inizing hormone,LH)、Ⅰ型前胶原氨基末端肽(Procollagen type I N-terminal propeptide,PINP)、骨保护素(Osteoprotegerin,OPG)、β胶原降解产物(Beta carboxyl terminal peptide of col-lagen,β-CTX)的含量。采用苏木精伊红(Hematoxylin-eosin,HE)染色观察各组大鼠股骨病理变化。通过Western blot检测股骨中PI3K和Akt蛋白的表达情况。结果与正常对照组比较,模型组大鼠股骨骨小梁数量减少,出现断裂,骨间隙增大,体重增加和血清FSH,LH,β-CTX水平升高,E2,PINP,OPG,p-PI3K/PI3K,p-Akt/Akt水平降低,差异有统计学意义(P<0.05);与模型组比较,更年安组和罗补甫克比日丸高剂量组大鼠股骨骨小梁数量增多,断裂现象减少,骨间隙减小,体重变化和FSH,LH水平降低,E2,PINP,OPG水平升高,此外,罗补甫克比日丸中、高剂量组大鼠股骨中p-PI3K/PI3K,p-Akt/Akt水平升高,血清β-CTX水平降低,差异有统计学意义(P<0.05)。结论罗补甫克比日丸能够改善更年期大鼠性激素紊乱,通过调控PI3K/Akt信号通路缓解骨代谢异常。Objective To study the effects of Luobufukebiri Pill on hormone secretion and bone metabolism in menopausal rats.Methods Six 2-month-old normal rats were selected as the normal control group(0.5%CMC Na).Thirty 12-month-old naturally aging rats with menstrual cycle disorders were selected as menopausal models by observing vaginal smears.The menopausal model rats were randomly divided into 5 groups:model group(0.5%CMC Na),low-dose group(Luobufukebiri Pill,236 mg/kg body weight),medium dose group(Luobufukebiri Pill,472 mg/kg body weight),high-dose group(Luobu-fukebiri Pill,945 mg/kg body weight),and Gengnian An group(Gengnian An Tablet,585 mg/kg body weight),with 6 rats in each group.They were orally administered once a day for 30 consecutive days.Ob-served and recorded the weight changes of each group of rats were observed and recorded during adminis-tration.used reagent kits to detect serum levels of Estradiol(E2),Follicle-stimulating hormone(FSH),Luteinizing hormone(LH),Procollagen type I N-terminal propeptide(PINP),Osteoprotegerin(OPG),andβ-carboxyl terminal peptide of collagen(β-CTX).Hematoxylin-eosin(HE)staining was used to ob-serve the pathological changes in the femur of each group of the rats.Western blot was used to detect the expression of PI3K and Akt proteins in the femur.Results Compared with normal control group,the model group rats reduced femoral trabecular number with increased fragmentation,increased bone space,increased body weight,and enhanced serum levels of FSH,LH andβ-CTX,along with decreased levels of E2,PINP,OPG,p-PI3K/PI3K and p-Akt/Akt,with statistically significant differences(P<0.05);Compared with the model group,the Gengnian An group and the high-dose Luobufukebiri Pill group showed increased femoral trabecular number,reduced fragmentation,decreased bone space,reduced body weight changes,and decreased serum FSH and LH levels,with increased E2,PINP and OPG levels,addi-tionally,the medium and high-dose Luobufukebiri Pill groups demonstrated increased p-PI3K/PI3K and p-Akt/Akt levels i
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