机构地区:[1]江西中医药大学,江西南昌330004 [2]江西省赣州市人民医院,江西赣州341000
出 处:《中药新药与临床药理》2021年第7期932-938,共7页Traditional Chinese Drug Research and Clinical Pharmacology
基 金:国家自然科学基金项目(81560723);江西中医药大学研究生创新基金项目(JZYC19S11)。
摘 要:目的探讨加味补阳还五汤对去卵巢大鼠骨质疏松症的影响。方法将60只雌性SD大鼠随机分为假手术组、模型组、福善美组(0.9 mg·kg^(-1))以及加味补阳还五汤高、中、低剂量组(18.18、9.09、4.545 g·kg^(-1)),每组10只。采用双侧卵巢摘除法建立绝经后骨质疏松症大鼠模型。造模1周后开始灌胃给药,每日1次,连续给药90 d。采用DPX-L双能X射线骨密度仪检测大鼠股骨的骨密度值;扫描电镜观察大鼠松质骨微结构变化;ELISA法检测大鼠骨髓内超氧化物歧化酶(SOD)、丙二醛(MDA)及髓过氧化酶(MPO)的含量;采用Western Blot法检测大鼠胫骨组织中骨形成蛋白2(BMP-2)、骨保护素(OPG)及Ⅰ型胶原蛋白(CollagenⅠ)表达情况。提取各组大鼠原代骨髓间充质干细胞(BMSCs),采用MTT法检测各组大鼠BMSCs生长速率,描绘生长速率曲线。结果与假手术组比较,去卵巢后大鼠的骨密度明显降低(P<0.01);大鼠股骨的骨小梁塌陷,无完整结构,有明显吸收陷窝;模型组大鼠骨髓内的MPO水平明显升高(P<0.05),而SOD活力明显降低(P<0.05),MDA含量升高但差异无统计学意义(P>0.05);大鼠胫骨组织中BMP-2及CollagenⅠ的蛋白表达明显下调(P<0.05),OPG蛋白表达有下调但差异无统计学意义(P>0.05);模型组第3~8天的BMSCs增殖速率均明显降低(P<0.01)。与模型组比较,各给药组大鼠的骨密度显著提高(P<0.01);松质骨微结构得到明显改善,骨小梁结构比较完整,壁厚且连接性较好;各给药组的骨髓内SOD活力均有所升高但差异无统计学意义(P>0.05),加味补阳还五汤高剂量组的MDA、MPO水平明显降低(P<0.05,P<0.01);加味补阳还五汤中、高剂量组去卵巢大鼠胫骨组织中BMP-2、OPG及CollagenⅠ的蛋白表达明显上调(P<0.05,P<0.01);各给药组第3~8天的BMSCs增殖速率均明显升高(P<0.01)。结论加味补阳还五汤可能通过上调骨组织中BMP-2、OPG及CollagenⅠ蛋白表达,促进BMSCs的增殖及骨向分化Objective To investigate the effect of modified Buyang Huanwu decoction on osteoporosis in ovariectomized rats.Methods Sixty female SD rats were randomly divided into Sham operation group,model group,Fushanmei group(0.9 mg·kg^(-1)),and modified Buyang Huanwu decoction high,medium and low dose groups(18.18,9.09,4.545 g·kg^(-1)),10 rats per group.Rat model of postmenopausal osteoporosis was established by bilateral ovarian extraction.One week after the model was established,the intragastric administration was started,once a day,for 90 consecutive days.DPX-L dual-energy X-ray bone densitometer was used to detect the bone mineral density of rat femur;scanning electron microscope was used to observe the microstructure changes of rat cancellous bone;the ELISA method was used to detect superoxide dismutase(SOD),malondialdehyde(MDA)and marrow peroxidase(MPO)in bone marrow of rats.Western Blot method was used to detect expression of bone morphogenetic protein(BMP-2),osteoprotegerin(OPG),and typeⅠcollagen(CollagenⅠ)in rat tibia tissue.The primary bone marrow mesenchymal stem cells(BMSCs)of each group of rats were extracted,and the growth rate of BMSCs of each group was detected by MTT method,and the growth rate curve was drawn.Results Compared with the Sham operation group,the bone mineral density of the rats after ovariectomy was significantly reduced(P<0.01);the trabecular bone of the rat femur was collapsed without a complete structure,and there were obvious resorption lacuna.The level of MPO in the bone marrow of the model group was significantly increased(P<0.05),while the SOD activity was significantly reduced(P<0.05),and the MDA content was increased but the difference was not statistically significant(P>0.05).The protein expression of BMP-2 and CollagenⅠin rat tibia tissue was significantly down-regulated(P<0.05),OPG protein expression was down-regulated but the difference was not statistically significant(P>0.05).The proliferation rate of BMSCs in the model group was significantly reduced on day 3-8(P<0.01
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