肾纤康通过下调COMP防治CKD-MBD大鼠的肾骨异常OA
Shenxiankang prevents and treats renal bone abnormalities in CKD-MBD rats by downregulating COMP
目的 探讨肾纤康对慢性肾病-矿物质和骨代谢异常(chronic kidney disease-mineral and bone disorder,CKD-MBD)的防治作用和潜在机制.方法 构建大鼠CKD-MBD动物模型,检测大鼠血清肌酐(Scr)、尿素氮(BUN)水平;ELISA检测大鼠血清中骨碱性磷酸酶(BALP)、全段甲状旁腺激素(iPTH)、维生素D3(VD3)、软骨寡聚基质蛋白(COMP)、成纤维细胞生长因子23(FGF23)、klotho、成纤维细胞生长因子受体1(FGFR1)含量;苏木素-伊红(HE)、Masson和PSR染色观察肾组织病理学改变;HE、Masson和TRAP染色观察股骨组织形态;显微CT(Micro-CT)分析股骨结构特性;实时荧光定量逆转录PCR(RT-qPCR)和Western Blot检测肾组织中COMP、FGF23、klotho、FGFR1 mRNA及蛋白水平;免疫组化观察肾和骨组织中上述分子的表达.结果 与模型组CKD-MBD大鼠相比,肾纤康可显著降低血清Scr、BUN、BALP、iPTH、COMP及FGF23水平(P＜0.01,P＜0.05),升高VD3、klotho及FGFR1水平(P＜0.01),减轻大鼠肾损伤、胶原纤维沉积及炎性浸润,改善骨质疏松与骨代谢,下调肾组织中COMP、FGF23的mRNA及蛋白表达(P＜0.01),上调klotho和FGFR1的mRNA及蛋白表达(P＜0.01,P＜0.05),免疫组化结果与分子检测趋势一致.结论 肾纤康能有效防治CKD-MBD大鼠的肾骨异常,其机制可能与下调COMP和调控FGF23-klotho信号轴有关,且肾纤康高剂量组效果最佳.
Objective To investigate the preventive effects and potential mechanisms of Shenxiankang in chronic kidney disease-mineral and bone disorder(CKD-MBD).Methods A rat model of CKD-MBD was established.Serum creatinine(Scr)and blood urea nitrogen(BUN)were measured.Serum levels of bone alkaline phosphatase(BALP),intact parathyroid hormone(iPTH),vitamin D3(VD3),cartilage oligomeric matrix protein(COMP),fibroblast growth factor 23(FGF23),klotho,and fibroblast growth factor receptor 1(FGFR1)were determined by ELISA.Histopathological changes in renal tissues were examined using hematoxylin-eosin(HE),Masson,and picrosirius red staining.Femoral tissue morphology was assessed by HE,Masson,and tartrate-resistant acid phosphatase staining,while femoral structural parameters were evaluated using micro-computed tomography.The mRNA and protein expression levels of COMP,FGF23,klotho,and FGFR1 in renal tissues were analyzed by quantitative real-time reverse transcription PCR(RT-qPCR)and Western Blot.In addition,the expression of these molecules in renal and bone tissues was examined by immunohistochemistry.Results Compared with CKD-MBD group rats,Shenxiankang treatment significantly reduced serum creatinine,blood urea nitrogen,bone alkaline phosphatase,intact parathyroid hormone,COMP,and FGF23(P＜0.01,P＜0.05),while significantly increasing serum VD3,klotho,and FGFR1(P＜0.01).Shenxiankang also alleviated renal injury,collagen fiber deposition,and inflammatory infiltration and improved osteoporosis and bone metabolic abnormalities.Furthermore,Shenxiankang downregulated mRNA and protein expression of COMP and FGF23 in renal tissues(P＜0.01),while upregulating mRNA and protein expression of klotho and FGFR1(P＜0.01,P＜0.05).Immunohistochemical findings were consistent with these molecular result.Conclusions Shenxiankang effectively prevents and treats renal and skeletal abnormalities in CKD-MBD rats.Its therapeutic effects may be associated with downregulation of COMP and modulation of the FGF23-klotho signaling axis.
谭碧玉;李树玲;唐伟力;杜小梅;刘建;张琼;胡琼丹
西南医科大学附属中医医院肾内科,四川 泸州 646000西南医科大学附属中医医院肾内科,四川 泸州 646000泸州市中医院骨一科,四川泸州 646000西南医科大学附属中医医院肾内科,四川 泸州 646000西南医科大学附属中医医院肾内科,四川 泸州 646000西南医科大学附属中医医院肾内科,四川 泸州 646000成都中医药大学附属医院肾病科,成都 610072||西南医科大学附属中医医院肾内科,四川 泸州 646000
生物科学
肾纤康慢性肾病-矿物质和骨代谢异常软骨寡聚基质蛋白FGF23-klotho轴肾骨异常
Shenxiankangchronic kidney disease-mineral and bone disordercartilage oligomeric matrix proteinFGF23-klotho axisrenal bone abnormality
《中国实验动物学报》 2026 (4)
483-495,13
国家自然科学基金项目(82205002),四川省中医药管理局科技研究专项项目(2024MS524),西南医科大学科技计划项目(2023ZD008),西南医科大学中西医结合专项(2024ZXYZX02,2023ZYQJ04).Funded by National Natural Science Foundation of China(82205002),Sichuan Provincial Administration of Traditional Chinese Medicine Science Research Special Project(2024MS524),Southwest Medical University Science and Technology Planning Project(2023ZD008),Southwest Medical University Special Project on Integrated Traditional Chinese and Western Medicine(2024ZXYZX02,2023ZYQJ04).
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