人参皂苷 Rg3对骨质疏松大鼠骨代谢及肠钙吸收功能的影响

周红, 张亚维, 张堃, 白登彦

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重庆医科大学学报 ›› 2024, Vol. 49 ›› Issue (02) : 141-146. DOI: 10.13406/j.cnki.cyxb.003425
基础研究 DOI:10.13406/j.cnki.cyxb.003425

人参皂苷 Rg3对骨质疏松大鼠骨代谢及肠钙吸收功能的影响

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Effects of Ginsenoside Rg3 on bone metabolism and intestinal calcium absorption in osteoporosis rats

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摘要

目的 探究人参皂苷Rg3对骨质疏松(osteoporosis,OP)大鼠骨代谢及肠钙吸收功能的影响。 方法 60只SPF级雌性Wistar大鼠,按照随机数字法分为空白组、模型组、阳性组、实验组,每组大鼠各15只。除空白组外,其他大鼠均采用去势(OVX法)法制备OP大鼠模型。造模成功后,空白组及模型组生理盐水灌胃[10 mL/(kg·d)],阳性组给予阿仑膦酸钠维D3灌服(每周6.25 mg/kg),实验组给予人参皂苷Rg3[80 mg/(kg·d)]灌胃治疗,连续干预治疗12周。检测各组股骨、胫骨骨密度变化,酶联免疫法检测大鼠血清中骨保护素(osteoclastogenesis inhibitory factor,OPG)、Ⅰ型前胶原氨基末端肽(procollagen type Ⅰ N-terminal propeptide,PINP)、抗酒石酸酸性磷酸酶(tartrate resistant acid phosphatase,TRACP)、I型胶原交联C-末端肽(Type Ⅰcollagen carboxy-terminal peptide,CTX-I)含量变化;原位末端标记法(TdT-mediated dUTP nick end labeling,TUNEL)法分析各组肠黏膜组织细胞凋亡情况;Masson法分析各组肠黏膜组织纤维病理改变;免疫组化法检测各组肠黏膜组织中维生素D膜相关快速反应结合蛋白(membrane-associated rapid response steroid-binding,1,25-D3-MARRS)蛋白表达;蛋白免疫印迹法及RT-PCR法检测各组Jagged1、Notch1、Hes1蛋白及mRNA表达水平。 结果 大鼠造模后股骨、胫骨骨密度明显下降,血清中OPG、PINP、TRACP及CTX-I含量明显变化(P<0.05);肠黏膜组织病理发生明显改变,组织纤维化增强,细胞凋亡程度增加;肠黏膜组织1,25-D3-MARRS蛋白表达降低(P<0.05)。治疗后与模型组对比,阳性组及实验组大鼠股骨、胫骨骨密度明显升高,血清中OPG、PINP、TRACP及CTX-I含量明显改善(P<0.05);肠黏膜组织病理发生明显改善,纤维化降低,细胞凋亡程度降低;肠黏膜组织中Jagged1、Notch1、Hes1蛋白及mRNA表达明显改善(P<0.05)。 结论 人参皂苷 Rg3能够提高OP大鼠骨密度,减轻肠黏膜组织细胞凋亡及组织纤维化,增加肠黏膜1,25D3-MARRS蛋白表达,改善肠道钙吸收。

Abstract

Objective To explore the effect of Ginsenoside Rg3 on bone metabolism and intestinal calcium absorption in osteoporosis(OP) rats. Methods 60 SPF grade female Wistar rats were randomly divided into blank group,model group,positive group,and experimental group,with 15 rats in each group. Except for the blank group,all other rats were used to prepare OP rat models using the OVX method. After successful modeling,the blank group and the model group were given normal saline by gavage[10 mL/(kg·d)],the positive group was given alendronic acid sodium and vitamin D3 by gavage[6.25 mg/(kg·w)],and the experimental group was given ginsenoside Rg3[80 mg/(kg·d)] by gavage for 12 consecutive weeks. Bone mineral density changes of femur and tibia in each group were detected. Serum osteoprotegerin(OPG),procollagen type I N-terminal peptide(PINP),tartrate resistant acid phosphatase(TRACP) Changes in the content of Type I collagen cross-linked C-terminal peptide(CTX-I);TUNEL method was used to analyze the apoptosis of intestinal mucosal tissue cells in each group;Masson's method was used to analyze the pathological changes of intestinal mucosal tissue fibers in each group;Immunohistochemical method was used to detect the protein expression of vitamin D membrane associated rapid response steroid binding(1,25-D3-MARRS) in intestinal mucosa tissues of each group;Protein immunoblotting and RT-PCR were used to detect the expression levels of Jagged1,Notch1,Hes1 protein and mRNA in each group. Results After modeling,the bone density of the femur and tibia in rats decreased significantly,and the levels of OPG,PINP,TRACP,and CTX-I in serum showed significant changes(P<0.05);Significant pathological changes occur in the intestinal mucosa tissue,with increased fibrosis and increased degree of cell apoptosis;The expression of 1,25-D3-MARRS protein in intestinal mucosal tissue decreased(P<0.05). After treatment,compared with the model group,the bone density of the femur and tibia of the positive and experimental groups were significantly increased,and the serum levels of OPG,PINP,TRACP,and CTX-I were significantly improved(P<0.05);The pathological changes of intestinal mucosa tissue have significantly improved,with reduced fibrosis and reduced degree of cell apoptosis;The expression of Jagged1,Notch1,Hes1 proteins and mRNA in intestinal mucosal tissue was significantly improved(P<0.05). Conclusion Ginsenoside Rg3 can increase bone density of OP rats,reduce apoptosis and fibrosis of intestinal mucosa,increase the expression of 1,25D3-MARRS protein in intestinal mucosa,and improve intestinal calcium absorption.

关键词

骨质疏松 / 人参皂苷Rg3 / 肠钙吸收 / 骨密度 / 维生素D膜相关快速反应结合蛋白

Key words

osteoporosis / ginsenoside Rg3 / intestinal calcium absorption / bone density / vitamin D membrane associated rapid response steroid binding

中图分类号

R285

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周红 , 张亚维 , 张堃 , . 人参皂苷 Rg3对骨质疏松大鼠骨代谢及肠钙吸收功能的影响. 重庆医科大学学报. 2024, 49(02): 141-146 https://doi.org/10.13406/j.cnki.cyxb.003425
Zhou Hong, Zhang Yawei, Zhang Kun, et al. Effects of Ginsenoside Rg3 on bone metabolism and intestinal calcium absorption in osteoporosis rats[J]. Journal of Chongqing Medical University. 2024, 49(02): 141-146 https://doi.org/10.13406/j.cnki.cyxb.003425

参考文献

1
林贤灿,陈桐莹,林燕平,等. 原发性骨质疏松症的中医认识与探索[J]. 中国骨质疏松杂志202329(6):870-874,885.
Lin XC Chen TY Lin YP,et al. TCM cognition and exploration of primary osteoporosis[J]. Chin J Osteoporos202329(6):870-874,885.
2
王 林,李春霖. 钙剂和维生素D在老年骨质疏松症中的应用[J]. 中国临床保健杂志202225(1):30-33.
Wang L Li CL. Application of calcium and vitamin D in elderly patients with osteoporosis[J]. Chin J Clin Healthc202225(1):30-33.
3
Kang S Park SJ Lee AY,et al. Ginsenoside Rg3 promotes inflammation resolution through M2 macrophage polarization[J]. J Ginseng Res201842(1):68-74.
4
马伟凤,王 亮,马彦巧,等. 人参皂苷Rg3通过调节AMPK/mTOR信号通路提高骨质疏松老年大鼠骨密度及骨代谢[J].广州中医药大学学报202340(1):163-169.
Ma WF Wang L Ma YQ,et al. Ginsenoside Rg3 enhances bone mineral density and bone metabolism in osteoporotic aged rats through regulation of AMPK/mTOR signaling pathway[J].J Guangzhou Univ Tradit Chin Med202340(1):163-169.
5
Al-Dhubiab BE Patel SS Morsy MA,et al.The beneficial effect of boswellic acid on bone metabolism and possible mechanisms of action in experimental osteoporosis[J].Nutrients202012(10):3186.
6
McClung MR Clark AL.Osteoanabolic therapy for osteoporosis in women[J].Climacteric202225(1):60-66.
7
毛筱涵,靳雅倩,丰天宇,等. 人参皂苷Rg3抑制人骨肉瘤143B细胞的增殖、迁移和侵袭并促进其凋亡[J]. 肿瘤202040(4):233-244.
Mao XH Jin YQ Feng TY,et al.Ginsenoside Rg3 inhibits the proliferation,migration,invasion of human osteosarcoma 143B cells and promotes apoptosis[J].Tumor202040(4):233-244.
8
岳宗进,刘汝银,于 露,等.人参皂苷Rg1通过miR-138-5p/SIRT1轴诱导骨髓间充质干细胞向髓核样细胞增殖分化[J].中国现代应用药学202239(1):27-35.
Yue ZJ Liu RY Yu L,et al.Ginsenoside Rg1 induces the proliferation and differentiation of bone marrow mesenchymal stem cells into nucleus pulposusk-like cells through the miR-138-5p/SIRT1 axis[J].Chin J Mod Appl Pharm202239(1):27-35.
9
Sun DD Zou YF Song L,et al.A cyclodextrin-based nanoformulation achieves co-delivery of ginsenoside Rg3 and quercetin for chemo-immunotherapy in colorectal cancer[J].Acta Pharm Sin B202212(1):378-393.
10
陈德云,沈志强,何 波. 人参皂苷活性单体-20(R)-人参皂苷Rg3药理作用及其机制的研究进展[J]. 天然产物研究与开发201931(7):1285-1290.
Chen DY Shen ZQ He B. Advances in the research of pharmacological effects and its mechanisms of 20(R)-ginsenoside Rg3 [J]. Nat Prod Res Dev201931(7):1285-1290.
11
任国臣,刘 刚,赵丹,等. 钙对人系膜细胞增殖及1,25-D3-MARRS蛋白表达的影响[J]. 安徽医科大学学报201954(9):1396-1399.
Ren GC Liu G Zhao D,et al. Effects of calcium on proliferation of human mesangial cells and the expression of 1,25-D3-MARRS[J].Acta Univ Med Anhui201954(9):1396-1399.
12
李希宁,翁 伟,沈哲源,等. 雌二醇联合1,25-二羟维生素D3对绝经后骨质疏松症大鼠的治疗作用[J]. 吉林大学学报(医学版)202147(4):857-864.
Li XN Weng W Shen ZY,et al.Therapeutic effect of estradiol combined with 1,25-dihydroxyvitamin D3 on postmenopausal osteoporosis in rats[J].J Jilin Univ Med Ed202147(4):857-864.
13
石 娜,朱崇田,欧阳钢. 电针对绝经后骨质疏松症模型大鼠肠黏膜维生素D膜相关性快速反应类固醇结合蛋白表达的影响[J].上海针灸杂志202241(6):610-616.
Shi N Zhu CT Ouyang G.Effect of electroacupuncture on the expression of vitamin D membrane-associated rapid response steroid-binding protein in intestinal mucosa of postmenopausal osteoporosis rats[J].Shanghai J Acupunct Moxibustion202241(6):610-616.
14
Xing Wanhong, Ye Yujiao, Tang Jie,et al. Down-Regulation of Notch Effects on Vascular Endothelial Growth Factor Pathway and Cell Proliferation of Bone Marrow Mesenchymal Stem Cells Co-Cultured with Endothelial Progenitor Cells[J].JOURNAL OF BIOMATERIALS AND TISSUE ENGINEERING202010(9):PP1306-1311.
15
卫 莹,刘师伟,段瑞雪,等. 人脐带间充质干细胞通过调控OPG/RANKL比值对骨质疏松大鼠的影响及机制研究[J]. 重庆医科大学学报202247(5):503-510.
Wei Y Liu SW Duan RX,et al. Effects and mechanism of human umbilical cord mesenchymal stem cells on osteoporosis rats by regulating the ratio of osteoprotegerin/receptor activator of nuclear factor-κB ligand[J]. J Chongqing Med Univ202247(5):503-510.
16
Hansen D Bressendorff I Nordholm A,et al. Circadian rhythm of markers of bone turnover in patients with chronic kidney disease[J].Bone Rep202216:101593.
17
Canalis E Schilling L Yee SP,et al. Hajdu Cheney mouse mutants exhibit osteopenia,increased osteoclastogenesis,and bone resorption[J]. J Biol Chem2016291(4):1538-1551.
18
Guo L Zhen QL Zhen XY,et al. A network pharmacology approach to explore and validate the potential targets of ginsenoside on osteoporosis[J]. Int J Immunopathol Pharmacol202236:3946320221107239.

基金

甘肃省自然科学基金资助项目(21CX1RA176)

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