文献类型：期刊文献

中文题名：金匮肾气丸对糖尿病肾病性骨质疏松大鼠的影响及机制

英文题名：Effects and its mechanism of Jingui shenqi pill on diabetic nephropathy-related osteoporosis in rats

作者：丁文君[1];沈明霞[2];高永蕊[3]

第一作者：丁文君

机构：[1]甘肃省中医药研究院暨甘肃省中医院肾病科,兰州730050;[2]甘肃中医药大学附属医院全科医学科,兰州730020;[3]甘肃中医药大学中西医结合学院,兰州730020

第一机构：甘肃省中医药研究院暨甘肃省中医院肾病科,兰州730050

年份：2025

卷号：36

期号：16

起止页码：2000

中文期刊名：中国药房

外文期刊名：China Pharmacy

收录：;北大核心:【北大核心2023】；

基金：甘肃省自然科学基金项目(No.22JR5RA642)。

语种：中文

中文关键词：金匮肾气丸;糖尿病肾病性骨质疏松;骨代谢;RANKL/RANK/OPG信号通路

外文关键词：Jingui shenqi pill;diabetic nephropathyrelated osteoporosis;bone metabolism;RANKL/RANK/OPG signaling pathway

摘要：目的探讨金匮肾气丸对糖尿病肾病性骨质疏松(DNOP)大鼠的影响及潜在机制。方法将大鼠随机分为空白对照组,对照组,模型组,金匮肾气丸低、中、高剂量组(0.62、1.24、2.48 g/kg)和阳性对照组(地舒单抗3 mg/kg),每组12只。除空白对照组和对照组外,其余各组均以高糖高脂饲料、3%果糖溶液喂养+链脲佐菌素溶液腹腔注射的方式构建DNOP大鼠模型。造模成功后第2天,金匮肾气丸低、中、高剂量组和阳性对照组大鼠分别灌胃或皮下注射相应药液,每天1次,连续8周。末次给药后,检测各组大鼠的骨密度(BMD)、血清骨代谢相关指标[骨钙素(OC)、钙、磷、碱性磷酸酶(ALP)、抗酒石酸酸性磷酸酶(TRAP)],观察其右股骨组织病理学改变,检测其左股骨组织中核因子κB受体激活蛋白配体(RANKL)/核因子κB受体激活蛋白(RANK)/护骨因子(OPG)信号通路相关mRNA及蛋白的表达情况。结果与空白对照组、对照组比较,模型组大鼠骨小梁断裂及结构受损严重,骨组织间隙明显;BMD、ALP活性、OPG mRNA及蛋白的表达均显著降低或下调(P<0.05);OC、钙、磷水平,TRAP活性,RANKL、RANK mRNA及蛋白的表达均显著升高或上调(P<0.05)。与模型组比较,金匮肾气丸各剂量组大鼠骨小梁数有所增加,骨小梁排列趋于整齐、致密;上述指标普遍回调,且有一定的剂量依赖性(P<0.05)。结论金匮肾气丸可促进DNOP大鼠骨生成,调节骨代谢平衡;上述作用可能与下调RANKL、RANK表达,上调OPG表达有关。
OBJECTIVE To explore the effect of Jinkui shenqi pill and its potential mechanism on diabetic nephropathy-related osteoporosis(DNOP)in rats.METHODS The rats were randomly divided into blank control group,control group,model group,Jingui shenqi pill low-,medium-and high-dose groups(0.62,1.24,2.48 g/kg),and positive control group(denosumab 3 mg/kg),with 12 cases in each group.Except for the blank control group and the control group,models of DNOP were constructed in the remaining groups by high-glucose and high-fat forage,3%fructose solution for feeding+intraperitoneal injection of streptozotocin solution.At 2 d after successful molding,Jingui shenqi pill low-,medium-and high-dose groups,and positive control group were given intragastric administration or subcutaneous injection of the corresponding drugs,once a day,for consecutive 8 weeks.After the last administration,bone mineral density(BMD)and serum bone metabolism-related indexes[osteocalcin(OC),calcium,phosphorus,alkaline phosphatase(ALP),tartrate-resistant acid phosphatase(TRAP)]were detected.The pathological changes of right femoral tissues were observed,and the expressions of receptor activator of NF-κB ligand(RANKL)/receptor activator of NF-κB(RANK)/osteoprotegerin(OPG)pathway-related mRNAs and proteins in left femoral tissues were detected.RESULTS Compared with the blank control group and the control group,there was rupture of bone trabecula and severe structural damage in the model group,and tissue space was obvious.BMD and ALP activities,mRNA and protein expressions of OPG were significantly decreased or down-regulated,while the levels of OC,calcium and phosphorus,TRAP activity,mRNA and protein expressions of RANKL and RANK were significantly increased or up-regulated(P<0.05).Compared with the model group,the number of bone trabeculae was increased in all Jingui shenqi pill groups,and the arrangement of bone trabeculae was more regular and dense.The above indexes generally were improved in a certain dose-dependent manner(P<0.05).CONCLUSIONS Jingui shenqi pill can promote osteogenesis and regulate the balance of bone metabolism in DNOP rats,which may be related to down-regulating the expressions of RANKL and RANK,and up-regulating the expression of OPG.