Effect of Sanhuang Tangshenkang on Wnt/<italic style="font-style: italic">β</italic>-catenin Signaling Pathway in Bone Tissue of Diabetic Rats

SUN Liya; GU Liyan; LIU Bei; WANG Jiaxi; FENG Yinan; XI Yue

doi:10.13422/j.cnki.syfjx.20230842

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Effect of Sanhuang Tangshenkang on Wnt/β-catenin Signaling Pathway in Bone Tissue of Diabetic Rats

更新时间：2023-08-22

- Effect of Sanhuang Tangshenkang on Wnt/β-catenin Signaling Pathway in Bone Tissue of Diabetic Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 18, Pages: 69-77(2023)
- 作者机构：
  
  1.辽宁中医药大学，沈阳 110847
  2.辽宁中医药大学中医脏象理论及应用教育部重点实验室，沈阳 110847
  3.沈北新区卫生健康监督中心，沈阳 110127
  4.锦州医科大学附属第三医院，辽宁锦州 121001
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230842
  CLC： R2-0;R33;R587.1;R289;R692
- Published：20 September 2023，
  
  Published Online：06 July 2023，
  
  Received：28 March 2023，
- 稿件说明：
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孙立亚,谷丽艳,刘北等.三黄糖肾康对糖尿病大鼠骨组织Wnt/β-catenin信号通路的影响[J].中国实验方剂学杂志,2023,29(18):69-77.

SUN Liya,GU Liyan,LIU Bei,et al.Effect of Sanhuang Tangshenkang on Wnt/β-catenin Signaling Pathway in Bone Tissue of Diabetic Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(18):69-77.
孙立亚,谷丽艳,刘北等.三黄糖肾康对糖尿病大鼠骨组织Wnt/β-catenin信号通路的影响[J].中国实验方剂学杂志,2023,29(18):69-77. DOI： 10.13422/j.cnki.syfjx.20230842.

SUN Liya,GU Liyan,LIU Bei,et al.Effect of Sanhuang Tangshenkang on Wnt/β-catenin Signaling Pathway in Bone Tissue of Diabetic Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(18):69-77. DOI： 10.13422/j.cnki.syfjx.20230842.

摘要

目的

观察三黄糖肾康对糖尿病大鼠骨组织Wnt/

-连环蛋白（

-catenin）信号通路的影响。

方法

采用高糖高脂饮食4周联合左下腹腔内注射新鲜配制的2%链脲佐菌素（pH 4.5）30 mg·kg

-1

体质量制备糖尿病模型，成模大鼠按血糖水平随机分为模型组、三黄糖肾康低、高剂量组（12.8、38.4 g·kg

-1

）、骨疏康组（1.8 g·kg

-1

），另设同周龄喂食普通饲料大鼠为空白组。各组予相应药物或生理盐水灌胃12周后，全自动生化仪检测各组大鼠空腹血糖（FBG）；酶联免疫吸附测定法（ELISA）检测血清空腹胰岛素（FINS）、骨特异性碱性磷酸酶（BALP）、抗酒石酸酸性磷酸酶（TRAP）；计算机微断层扫描（Micro-CT）扫描大鼠股骨，观察骨组织微结构，检测骨密度（BMD）；苏木素-伊红（HE）染色、番红O-固绿染色观察大鼠股骨组织病理变化；免疫组化（IHC）和蛋白免疫印迹法（Western blot）检测Wnt3a、低密度脂蛋白受体相关蛋白5（LRP-5）及

-catenin蛋白的表达。

结果

与空白组比较，模型组大鼠FBG、FINS、TRAP显著升高（

0.01），BALP显著降低（

0.01），BMD显著降低（

0.01），骨小梁结构松散不规则，细长疏稀，出现断裂，脂滴增多，Wnt3a、LRP-5和

-catenin蛋白表达下降（

0.05，

0.01）；与模型组比较，三黄糖肾康低、高剂量组FBG降低、BALP升高（

0.05），三黄糖肾康低剂量组FINS降低（

0.05），各给药组TRAP均显著降低（

0.01）；各给药组BMD均有不同程度提高（

0.05，

0.01）；各给药组大鼠股骨骨小梁增多、增粗，排列较紧密、整齐，脂滴数量减少，骨微结构形态得到一定的改善；各给药组Wnt3a、LRP-5和

-catenin蛋白平均光密度值均有不同程度提高（

0.05，

0.01）；Wnt3a、LRP-5和

-catenin蛋白表达升高（

0.05，

0.01）。

结论

三黄糖肾康可能通过提高骨组织Wnt3a、LRP-5及

-catenin蛋白的表达，调节Wnt/

-catenin信号传导通路的失调状态，促进骨形成，减少骨吸收，降低血糖，从而达到防治糖尿病骨质疏松症的效果。

Abstract

Objective

To observe the effect of Sanhuang Tangshenkang on the Wnt/

-catenin signaling pathway in the bone tissue of diabetic rats.

Method

A high-sugar and high-fat diet was administered for 4 weeks， along with intraperitoneal injection of freshly prepared 2% streptozotocin （pH 4.5） at 30 mg·kg

-1

body weight to induce a diabetes model in rats. The rats with diabetes were randomly divided into model group， low- and high-dose Sanhuang Tangshenkang groups （12.8， 38.4 g·kg

-1

）， and Gushukang group （1.8 g·kg

-1

） according to the blood glucose level. Rats of the same age were fed on a regular diet and assigned to the control group. After 12 weeks of respective treatments with drugs or physiological saline， the fasting blood glucose （FBG） levels of the rats were measured using an automated biochemical analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to detect fasting serum insulin （FINS）， bone-specific alkaline phosphatase （BALP）， and tartrate-resistant acid phosphatase （TRAP） levels. Micro-computed tomography （Micro-CT） was used to scan the femurs of rats to observe bone tissue microstructure and measure bone mineral density （BMD）. Hematoxylin-eosin （HE） staining and safranin O/fast green staining were performed to observe pathological changes in the femoral bone tissue. Immunohistochemistry （IHC） and Western blot were used to detect the expression of Wnt3a， low-density lipoprotein receptor-related protein 5 （LRP-5）， and

-catenin proteins.

Result

Compared with the control group， the model group showed a significant increase in FBG， FINS， and TRAP levels （

0.01）， a significant decrease in BALP level （

0.01）， a significant decrease in BMD （

0.01）， and disorganized， elongated， and sparse bone trabecular structures with fractures and increased lipid droplets. Additionally， the expression of Wnt3a， LRP-5， and

-catenin proteins decreased （

0.05，

0.01）. Compared with the model group， the low- and high-dose Sanhuang Tangshenkang groups showed a reduction in FBG and an increase in BALP （

0.05）. The low-dose Sanhuang Tangshenkang group also exhibited a decrease in FINS （

0.05）. All treatment groups showed a significant decrease in TRAP （

0.01）， varying degrees of improvement in BMD （

0.05，

0.01））， increased and denser bone trabeculae with more regular arrangements and reduced lipid droplets， and improved bone microstructure morphology. The average optical density values of Wnt3a， LRP-5， and

-catenin proteins were significantly increased in all drug-treated groups （

0.05，

0.01）， and the expression of Wnt3a， LRP-5， and

-catenin proteins was elevated （

0.05，

0.01）.

Conclusion

Sanhuang Tangshenkang may regulate the imbalance of the Wnt/

-catenin signaling pathway by increasing the expression of Wnt3a， LRP-5， and

-catenin proteins in bone tissue， which may promote bone formation， reduce bone resorption， and lower blood glucose levels， thereby achieving the effect of preventing and treating diabetic osteoporosis.

关键词

糖尿病骨质疏松症三黄糖肾康Wnt/β-连环蛋白信号通路

Keywords

diabetesosteoporosisSanhuang TangshenkangWnt/β-cateninsignaling pathway

references

CHO N H，SHAW J E，KARURANGA S，et al.IDF diabetes atlas： Global estimates of diabetes prevalence for 2017 and projections for 2045［J］.Diabetes Res Clin Pract，2018，138：271-281.

MONTAGNANI A，GONNELLI S，ALESSANDRI M，et al.Osteoporosis and risk of fracture in patients with diabetes：An update［J］.Aging Clin Exp Res，2011，23（2）：84-90.

QI S，HE J，ZHENG H，et al.Icariin prevents diabetes-induced bone loss in rats by reducing blood glucose and suppressing bone turnover［J］.Molecules，2019，24（10）：1871

QI 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.

FERRARI S L，ABRAHAMSEN B，NAPOLI N，et al.Diagnosis and management of bone fragility in diabetes：An emerging challenge［J］.Osteoporos Int，2018，29（12）：2585-2596.

FARSANI Z H，BANITALEBI E，FARAMARZI M，et al.Effects of different intensities of strength and endurance training on some osteometabolic miRNAs， Runx2 and PPARγ in bone marrow of old male wistar rats［J］.Mol Biol Rep，2019，46（2）：2513-2521.

DENG Q，LI P，CHE M，et al.Activation of hedgehog signaling in mesenchymal stem cells induces cartilage and bone tumor formation via Wnt/β-catenin［J］.Elife，2019，8

MOLAGODA I，KARUNARATHNE W，CHOI Y H，et al.Fermented oyster extract promotes osteoblast differentiation by activating the Wnt/β-catenin signaling pathway， leading to bone formation［J］.Biomolecules，2019，9（11）：711

PORTAL-NUNEZ S，LOZANO D，DE CASTRO L F，et al.Alterations of the Wnt/beta-catenin pathway and its target genes for the N- and C-terminal domains of parathyroid hormone-related protein in bone from diabetic mice［J］.FEBS Lett，2010，584（14）：3095-3100.

李娜，奚悦.三黄糖肾康颗粒对2型糖尿病大鼠骨质血清淀粉样蛋白A影响［J］.中医药临床杂志，2017，29（5）：647-649.

王静怡，奚悦.三黄糖肾康对2型糖尿病并发骨质疏松症大鼠瘦素表达的影响研究［J］.中国全科医学，2015（24）：2966-2970，2975.

王冠，王静怡，奚悦.三黄糖肾康对2型糖尿病大鼠骨组织肿瘤坏死因子-α、白细胞介素-6表达的影响［J］.天津医药，2015，43（11）：1292-1295.

李娜.三黄糖肾康对2型糖尿病大鼠骨质A-SAA和IL-6表达的影响［D］.沈阳：辽宁中医药大学， 2017.

王颖，戚瑞，张磊，等.鱼油对高脂喂养加小剂量STZ诱导的2型糖尿病大鼠血脂及肝脏的影响［J］.现代生物医学进展，2017，17（33）：6406-6411.

唐辉，姚志浩，罗道文，等.高脂高糖饮食结合链脲佐菌素建立2型糖尿病性骨质疏松症大鼠模型［J］.中国组织工程研究，2021，25（8）：1207-1211.

张燕，杨秋萍，赵燕，等.2型糖尿病大鼠骨质疏松模型的建立［J］.中国组织工程研究，2016，20（40）：6041-6047.

YANG M，XIE J，LEI X，et al.Tubeimoside I suppresses diabetes-induced bone loss in rats， osteoclast formation， and RANKL-induced nuclear factor-κB pathway［J］.Int Immunopharmacol，2020，80：106202.

TAYLOR G S，MOSER O，SMITH K，et al.Bone turnover and metabolite responses to exercise in people with and without long-duration type 1 diabetes：A case-control study［J］.BMJ Open Diabetes Res Care，2020，8（2）：e001779

MEDERLE O A，BALAS M，IOANOVICIU S D，et al.Correlations between bone turnover markers， serum magnesium and bone mass density in postmenopausal osteoporosis［J］.Clin Interv Aging，2018，13：1383-1389.

LORENTZON M，BRANCO J，BRANDI M L，et al.Algorithm for the use of biochemical markers of bone turnover in the diagnosis， assessment and follow-up of treatment for osteoporosis［J］.Adv Ther，2019，36（10）：2811-2824.

GUO C J，XIE J J，HONG R H，et al.Puerarin alleviates streptozotocin （STZ）-induced osteoporosis in rats through suppressing inflammation and apoptosis via HDAC1/HDAC3 signaling［J］.Biomed Pharmacother，2019，115：108570.

SAMSULRIZAL N，GOH Y M，AHMAD H，et al.Ficus deltoidea promotes bone formation in streptozotocin-induced diabetic rats［J］.Pharm Biol，2021，59（1）：66-73.

XIE H，WANG Q，ZHANG X，et al.Possible therapeutic potential of berberine in the treatment of STZ plus HFD-induced diabetic osteoporosis［J］.Biomed Pharmacother，2018，108：280-287.

LU R，ZHENG Z，YIN Y，et al.Genistein prevents bone loss in type 2 diabetic rats induced by streptozotocin［J］.Food Nutr Res，2020，doi：10.29219/fnr.v64.3666http://dx.doi.org/10.29219/fnr.v64.3666.

LI H，CHU S，ZHAO H，et al.Effect of Zishen Jiangtang Pill， a Chinese herbal product， on rats with diabetic osteoporosis［J］.Evid Based Complement Alternat Med，2018，2018：7201914.

LIU M M，DONG R，HUA Z，et al.Therapeutic potential of Liuwei Dihuang pill against KDM7A and Wnt/β-catenin signaling pathway in diabetic nephropathy-related osteoporosis［J］.Biosci Rep，2020，doi：10.1042/BSR20201778http://dx.doi.org/10.1042/BSR20201778.

QU P，LI Y，HU X，et al.The effect of adiponectin via regulating the bone microenvironment oxidative stress on osteogenesis in type 2 diabetic rats［J］.Acta Endocrinol （Buchar），2021，17（2）：168-176.

ZHENG H X，CHEN J，ZU Y X，et al.Chondroitin sulfate prevents STZ induced diabetic osteoporosis through decreasing blood glucose， antioxidative stress，anti-inflammation and OPG/RANKL expression regulation［J］.Int J Mol Sci，2020，21（15）：5303.

孙立亚，奚悦.中药通过调控骨代谢相关信号通路治疗糖尿病骨质疏松的研究进展［J］.中成药，2022，44（8）：2580-2586.

CHEN Z，XUE J，SHEN T，et al.Curcumin alleviates glucocorticoid-induced osteoporosis through the regulation of the Wnt signaling pathway［J］.Int J Mol Med，2016，37（2）：329-338.

CHUNG H J，KIM W K，OH J，et al.Anti-osteoporotic activity of harpagoside by upregulation of the BMP2 and Wnt signaling pathways in osteoblasts and suppression of differentiation in osteoclasts［J］.J Nat Prod，2017，80（2）：434-442.

WILLIAMS B O.LRP5：From bedside to bench to bone［J］.Bone，2017，102：26-30.

CHANG M K，KRAMER I，KELLER H，et al.Reversing LRP5-dependent osteoporosis and SOST deficiency-induced sclerosing bone disorders by altering Wnt signaling activity［J］.J Bone Miner Res，2014，29（1）：29-42.

李沁园，代冬芳，吴佩锋，等，二十五味鬼臼丸通过Wnt/β-catenin信号通路改善去卵巢大鼠骨质疏松症［J］.中国实验方剂学杂志，2023，29（2）：59-65.

李翠娟，王琳，巩振东.固本活血壮骨颗粒对糖尿病大鼠成骨细胞Wnt/β-catenin信号传导通路的影响［J］.陕西中医药大学学报，2016，39（1）：102-105，108.

孙勤国，徐鸿婕，罗蒙，等.滋阴补肾方对糖尿病合并去卵巢骨质疏松大鼠的作用及对Wnt/β-catenin信号的影响［J］.中国骨质疏松杂志，2020，26（3）：419-424.

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⁰

Effect of Sanhuang Tangshenkang on Wnt/β-catenin Signaling Pathway in Bone Tissue of Diabetic Rats

DOI：10.13422/j.cnki.syfjx.20230842

摘要

Abstract

关键词

Keywords

references