Effects of SGLT2i on Bone Metabolism in Nephrotic Syndrome Model Rats

Abstract

Abstract:

〔Abstract〕 Objective： To study the effect of sodium glucose cotransporter 2 inhibitor（SGLT2i） canagliflozin on bone metabolism in rats with nephrotic syndrome（NS）. Methods： There were 42 male SD rats in total， among which 6 rats were randomly selected as NG group， and the other 36 rats were injected with adriamycin through tail vein for modeling and were randomly divided into 6 groups， i.e.， MG group（model group）， PG group（prednisone group）， LCG group（low-dose canagliflozin group）， HCG group（high-dose canagliflozin group）， LPCG group（low-dose canagliflozin+prednisone group） and HPCG group（high-dose canagliflozin+prednisone group）， with 6 rats in each group. The rats were treated by regular gavage every morning for 6 weeks. At the end of treatment， 24 h-UTP， urinary calcium， urinary phosphorus， serum albumin（ALB）， blood calcium， blood phosphorus， alkaline phosphatase（ALP） and bone mineral density were measured. Results： Compared with NG group， ALP level increased in MG， PG， HCG and HPCG groups， and pelvic bone mineral density decreased in all drug treatment groups， PG and HPCG group caused the decrease of systemic bone mineral content， trunk and rib bone mineral density. Compared with MG group， 24h-UTP level decreased and ALB level increased in all drug treatment groups.Urinary calcium level increased in LPCG and HPCG groups. Serum phosphorus level increased in PG group. Conclusion：canagliflozin can effectively reduce urinary protein and increase ALB. So it can be used in the treatment of NS， but it can cause the decrease of pelvic bone mineral density. High-dose canagliflozin or its combination with prednisone can also cause abnormal calcium and phosphorus metabolism， increase ALP， expand the range of bone mineral density decline， and increase the risk of osteoporosis.

Key words:

"> ">〔Key words">〕 sodium glucose cotransporter 2 inhibitor">； bone mineral density">； calcium and phosphorus metabolism">； nephrotic syndrome

CLC Number:

Hong Wenjuan, Zou Jiulin, Yu Zhuorui, Cheng Jiamao, He Minhua.

Effects of SGLT2i on Bone Metabolism in Nephrotic Syndrome Model Rats [J]. Journal of Dali University, 2022, 7(4): 21-25.

References

〔1〕 CASTAEDA A M， DUTRA-RUFATO A， JUAREZ M J， et al. Sodium-Glucose Cotransporter 2 Inhibitors （SGLT2i）： Renal Implications〔J〕. Int Urol Nephrol，2021，53（2）： 291-299.

〔2〕 NINEVI V， OMANOVI KOLARI T， ROGULJI H， et al. Renal Benefits of SGLT 2 Inhibitors and GLP-1 Receptor Agonists： Evidence Supporting a Paradigm Shift in the Medical Management of Type 2 Diabetes〔J〕. Int J Mol Sci，2019，20（23）：5831.

〔3〕 CHILTON R J. Effects of Sodium-Glucose Cotransporter-2 Inhibitors on the Cardiovascular and Renal Complications of Type 2 Diabetes〔J〕. Diabetes Obes Metab，2020，22（1）：16-29.

〔4〕 NEAL B， PERKOVIC V， MAHAFFEY K W， et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes〔J〕. N Engl J Med，2017，377（7）：644-657.

〔5〕贺升升，李爱平，张王宁，等. 阿霉素肾病模型及其病理机制研究进展〔J〕. 中草药，2018，49（22）：5426-5434.

〔6〕王嘉文，宋璐，赵良斌，等.补肾活血祛风方对阿霉素肾病大鼠的干预研究〔J〕. 中药与临床，2021，12（2）：26-29.

〔7〕 RAJASEKERAN H， CHERNEY D Z， LOVSHIN J A. Do Effects of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Diabetes Give Insight into Potential Use in Non-Diabetic Kidney Disease?〔J〕. Curr Opin Nephrol Hypertens，2017，26（5）：358-367.

〔8〕 BRADY J A， HALLOW K M. Model-Based Evaluation of Proximal Sodium Reabsorption Through SGLT2 in Health and Diabetes and the Effect of Inhibition With Canaglif-lozin 〔J〕. J Clin Pharmacol，2018，58（3）：377-385.

〔9〕 APALSET E M， LUNDE A， HOFF M， et al. Initiation of Anti-Osteoporotic Drugs in High-Risk Female Patients Starting Glucocorticoid Treatment： a Population Study in Norway〔J〕. Arch Osteoporos，2020，15（1）：1-13.

〔10〕 NI L， YUAN C， CHEN G， et al. SGLT2i： Beyond the Glucose-Lowering Effect〔J〕.Cardiovasc Diabetol，2020， 19（1）：98.

〔11〕 WIVIOTT S D， RAZ I， BONACA M P， et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes〔J〕. N Engl J Med，2019，380（4）：347-357.

〔12〕 PERKOVIC V， JARDINE M J， NEAL B， et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy〔J〕. N Engl J Med，2019，380（24）： 2295-2306.

[1]	Yang Limin. Independent Number and Independent Polynomial of Complete Product of Graph [J]. Journal of Dali University, 2023, 8(6): 1-8.
[2]	Zhou Bin. Research on the Solution of Pure Integer Programming Problem Based on Number Theory [J]. Journal of Dali University, 2023, 8(6): 14-19.
[3]	Chen Li, Zhu Xingwen, Zhang Chaoyuan. The High-Precision Runge-Kutta Method for Solving Two-Dimensional Acoustic Wave Equation [J]. Journal of Dali University, 2023, 8(6): 20-23.
[4]	Wu Guifeng, Hu Fa, Zeng Xin, Yang Dengqi, Li Xiaowei. MV-Raft： A New Consensus Algorithm forAllianceChain Based on Multidimensional Vectors [J]. Journal of Dali University, 2023, 8(6): 24-32.
[5]	Cui Maohuan, Rao Dingqi. Diversity and Faunal Characteristics of Amphibians and Reptiles in Lanping Yunling Provincial Nature Reserve [J]. Journal of Dali University, 2023, 8(6): 61-68.
[6]	Li Jia, Yang Yingfei. A Dynamic Study on Students' Physical Fitness inDaliUniversity [J]. Journal of Dali University, 2023, 8(6): 69-74.
[7]	Tang Liang, Lu Jingnan, Jiang Haifeng, Xue Jiuyang. Executive Political Connections， Changes in Environmental Regulatory Modes， and Corporate Environmental Investment [J]. Journal of Dali University, 2023, 8(6): 79-87.
[8]	Ma Chenyu, Liu Chaorui, Lü Jianguo, Zhou Dongyan, Ye Zhilan. Analysis of Yield and Agronomic Traits of Maize Hybrids Bred from Inbred Line 2408 [J]. Journal of Dali University, 2023, 8(6): 88-94.
[9]	Xiong Kai, Xiao Tianbao, Zeng Lian, Luo Zicheng, Yang Tao, Yang Shengbang. Therapeutic Effect of Miao Medicine Rubus pluribracteatus on Mice with Ulcerative Colitis [J]. Journal of Dali University, 2023, 8(4): 1-6.
[10]	Meng Dong, Li Ya, Wang Chongjuan, Tian Yong, Tian Yuncai, Wu Mingyi. Content Determination and Methodological Validation of Snail Glycosaminoglycan [J]. Journal of Dali University, 2023, 8(4): 7-12.
[11]	Wang Jinyu, Zhou Longlong, Wang Xuechang, Li Xiaodong, Geng Shuqiong, Xia Conglong. Investigation on the Mechanism of Lemai Granules in the Treatment of Vascular Dementia Based on Network Pharmacology and Molecular Docking [J]. Journal of Dali University, 2023, 8(4): 13-21.
[12]	Huang Shan, Jin Liquan, Yu Yu, Huang Ji, Zhang Junhua, Chen Yiming. Expression of SOX9 in the Directed Differentiation of Mouse Hepatic Oval Cell into Biliary Epithelial Cells [J]. Journal of Dali University, 2023, 8(4): 22-27.
[13]	Zhao Chunjing, Chen Weiguo, Bai li, Wu Youcong. Effects of Periplaneta americana Extract CⅡ-3 on the Biofilm Formation of Candida albicans [J]. Journal of Dali University, 2023, 8(4): 28-33.
[14]	Bai Zongkai, Lü Neng, Liu Runhua, Luo Yuanxi, Wu Qiuyue, Xu Jing, Wu Youcong. Investigation on the Carrier Rate and Antifungal Susceptibility of Yeast Species Isolated from External Urethral Meatus of Healthy College Students [J]. Journal of Dali University, 2023, 8(4): 34-38.
[15]	Gao Wenyu, Zeng Rong, Xu Mengna, Zhang Yuanyuan. Study on the Correlation between Polymorphism of EPAS1 Gene rs1868092 and High Altitude Polycythemia in Tibetan Population [J]. Journal of Dali University, 2023, 8(4): 39-42.