Page 54 - 《中国药房》2025年16期

金匮肾气丸对糖尿病肾病性骨质疏松大鼠的影响及机制
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丁文君 ，沈明霞 ，高永蕊（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
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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）
中图分类号 R965 文献标志码 A 文章编号 1001-0408（2025）16-2000-05
DOI 10.6039/j.issn.1001-0408.2025.16.08

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。
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

Effects and its mechanism of Jingui shenqi pill on diabetic nephropathy-related osteoporosis in rats
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DING Wenjun ，SHEN Mingxia ，GAO Yongrui（1. Dept. of Nephrology， Gansu Academy of Traditional Chinese
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Medicine&Gansu Provincial Hospital of Traditional Chinese Medicine， Lanzhou 730050， China；2. Dept. of
General Medicine， the Affiliated Hospital of Gansu University of Chinese Medicine， Lanzhou 730020， China；
3. College of Integrated Traditional Chinese and Western Medicine， Gansu University of Chinese Medicine，
Lanzhou 730020， China）

ABSTRACT 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.
KEYWORDS Jingui shenqi pill； diabetic nephropathy-
Δ 基金项目 甘肃省自然科学基金项目（No.22JR5RA642）
＊第一作者 副主任医师，硕士。研究方向：中西医结合糖尿病肾 related osteoporosis； bone metabolism； RANKL/RANK/OPG
脏疾病的临床与基础。E-mail：dwj0821@163.com signaling pathway

· 2000 · China Pharmacy 2025 Vol. 36 No. 16 中国药房 2025年第36卷第16期