
浏览全部资源
扫码关注微信
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
副主任医师,硕士。研究方向:中西医结合糖尿病肾脏疾病的临床与基础。E-mail:dwj0821@163.com
收稿日期:2025-04-08,
修回日期:2025-07-24,
录用日期:2025-07-25,
纸质出版日期:2025-08-30
移动端阅览
丁文君,沈明霞,高永蕊.金匮肾气丸对糖尿病肾病性骨质疏松大鼠的影响及机制[J].中国药房,2025,36(16):2000-2004.
DING Wenjun,SHEN Mingxia,GAO Yongrui.Effects and its mechanism of Jingui shenqi pill on diabetic nephropathy-related osteoporosis in rats[J].ZHONGGUO YAOFANG,2025,36(16):2000-2004.
丁文君,沈明霞,高永蕊.金匮肾气丸对糖尿病肾病性骨质疏松大鼠的影响及机制[J].中国药房,2025,36(16):2000-2004. DOI: 10.6039/j.issn.1001-0408.2025.16.08.
DING Wenjun,SHEN Mingxia,GAO Yongrui.Effects and its mechanism of Jingui shenqi pill on diabetic nephropathy-related osteoporosis in rats[J].ZHONGGUO YAOFANG,2025,36(16):2000-2004. DOI: 10.6039/j.issn.1001-0408.2025.16.08.
目的
2
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
2
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
2
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
2
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
2
To explore the effect of Jinkui shenqi pill and its potential mechanism on diabetic nephropathy-related osteoporosis (DNOP) in rats.
METHODS
2
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
2
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
2
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.
CLYNES M A , HARVEY N C , CURTIS E M , et al . The epidemiology of osteoporosis [J ] . Br Med Bull , 2020 , 133 ( 1 ): 105 - 117 .
COMPSTON J . Reducing the treatment gap in osteopo-rosis [J ] . Lancet Diabetes Endocrinol , 2020 , 8 ( 1 ): 7 - 9 .
JOHNSTON C B , DAGAR M . Osteoporosis in older adults [J ] . Med Clin N Am , 2020 , 104 ( 5 ): 873 - 884 .
QI S S , HE J , HAN H , et al . Anthocyanin-rich extract from black rice( Oryza sativa L. Japonica )ameliorates diabetic osteoporosis in rats [J ] . Food Funct , 2019 , 10 ( 9 ): 5350 - 5360 .
JIN C , TAN K , YAO Z , et al . A novel anti-osteoporosis mechanism of VK2:interfering with ferroptosis via AMPK/SIRT1 pathway in type 2 diabetic osteoporosis [J ] . J Agric Food Chem , 2023 , 71 ( 6 ): 2745 - 2761 .
刘维 , 郭婉容 , 黄莉吉 , 等 . 糖尿病肾病合并骨质疏松症的中医药研究进展 [J ] . 中国中西医结合肾病杂志 , 2022 , 23 ( 9 ): 842 - 843 .
李伟 , 李春根 , 穆晓红 , 等 . 基于网络药理学预测金匮肾气丸治疗骨质疏松症的作用机制 [J ] . 世界中医药 , 2021 , 16 ( 22 ): 3285 - 3291,3297 .
申继强 , 代冬芳 , 吴佩锋 , 等 . 藏药二十五味鬼臼丸通过OPG/RANKL/RANK通路对去卵巢骨质疏松大鼠骨代谢的干预作用 [J ] . 中华中医药杂志 , 2023 , 38 ( 11 ): 5495 - 5499 .
FATHY M A , ANBAIG A , ALJAFIL R , et al . Effect of liraglutide on osteoporosis in a rat model of type 2 diabetes mellitus:a histological,immunohistochemical,and biochemical study [J ] . Microsc Microanal , 2023 , 29 ( 6 ): 2053 - 2067 .
张倩 , 田升 , 张立娟 , 等 . 金匮肾气丸对去势大鼠骨质疏松症模型的干预研究 [J ] . 解剖学杂志 , 2021 , 44 ( 增刊1 ): 229 .
张倩 . 金匮肾气丸通过调控BMP/Smad信号通路防治绝经后骨质疏松症的机制研究 [D ] . 济南 : 山东中医药大学 , 2021 .
SHANG Q , ZHAO W H , SHEN G Y , et al . Jingui shenqi pills regulate bone-fat balance in murine ovariectomy-induced osteoporosis with kidney yang deficiency [J ] . Evid Based Complement Alternat Med , 2020 , 2020 : 1517596 .
杨晓净 , 邓向群 , 肖婷 , 等 . 基于RANKL/RANK/OPG信号通路探讨土贝母苷甲对糖尿病性骨质疏松大鼠骨质流失的影响 [J ] . 河北医药 , 2023 , 45 ( 2 ): 174 - 179 .
马素起 , 殷项远 , 王庆华 , 等 . 二甲双胍与振动干预对糖尿病伴发骨质疏松大鼠骨密度和糖代谢的作用 [J ] . 中华内分泌外科杂志 , 2021 , 15 ( 4 ): 403 - 406 .
王龙飞 , 高玉海 , 谢高倩 , 等 . 槲皮素改善骨质疏松的作用机制研究进展 [J ] . 现代药物与临床 , 2023 , 38 ( 3 ): 714 - 718 .
王雪峰 , 杨松 , 曹立新 , 等 . 山柰酚对卵巢去势大鼠的促骨胶原生成和减少骨小梁丢失的保护作用研究 [J ] . 中国临床药理学杂志 , 2020 , 36 ( 10 ): 1302 - 1305 .
耿秋东 , 葛海雅 , 王和鸣 , 等 . 基于网络药理学探讨龟鹿二仙胶治疗骨关节炎的作用及机制 [J ] . 中国组织工程研究 , 2021 , 25 ( 8 ): 1229 - 1236 .
李伟杰 , 梁润英 . 金匮肾气丸防治骨质疏松症的机制研究 [J ] . 中国骨质疏松杂志 , 2022 , 28 ( 1 ): 89 - 97 .
ZHU S A , ZHU J X , ZHEN G H , et al . Subchondral bone osteoclasts induce sensory innervation and osteoarthritis pain [J ] . J Clin Invest , 2019 , 129 ( 3 ): 1076 - 1093 .
KIM J H , KIM M , JUNG H S , et al . Leonurus sibiricus L. ethanol extract promotes osteoblast differentiation and inhibits osteoclast formation [J ] . Int J Mol Med , 2019 , 44 ( 3 ): 913 - 926 .
SEO I B , LEE K P , PARK S Y , et al . Therapeutic effect of Shinkiwhan,herbal medicine,regulates OPG/RANKL/RANK system on ovariectomy-induced bone loss rat [J ] . Phys Act Nutr , 2020 , 24 ( 3 ): 19 - 24 .
0
浏览量
19
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
公网安备50010302001817