Mechanism of Astragaloside IV on diabetic nephropathy induced by Streptozotocin in rats

HUANG Li-xia; LI xin; ZHANG Shu; FAN Yu-yan

doi:10.16025/j.1674-1307.2023.04.014

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Mechanism of Astragaloside IV on diabetic nephropathy induced by Streptozotocin in rats

更新时间：2023-06-16

- Mechanism of Astragaloside IV on diabetic nephropathy induced by Streptozotocin in rats
- Beijing Journal of Traditional Chinese Medicine Vol. 42, Issue 4, Pages: 403-407(2023)
- 作者机构：
  
  1.首都医科大学附属北京天坛医院中医针灸科，北京 100070
  2.中日友好医院临床医学研究所，北京 100029
- 作者简介：
- 基金信息：
- DOI：10.16025/j.1674-1307.2023.04.014
  CLC：
- Published：25 April 2023，
  
  Received：18 March 2022，
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黄利霞，李忻，张舒，等.黄芪甲苷对链脲佐菌素诱导糖尿病肾病大鼠的作用机制［J］.北京中医药，2023，42（4）：403-407.

HUANG Li-xia,LI xin,ZHANG Shu,et al.Mechanism of Astragaloside IV on diabetic nephropathy induced by Streptozotocin in rats[J]. Beijing Journal of Traditional Chinese Medicine,2023,42(04):403-407.
黄利霞，李忻，张舒，等.黄芪甲苷对链脲佐菌素诱导糖尿病肾病大鼠的作用机制［J］.北京中医药，2023，42（4）：403-407. DOI： 10.16025/j.1674-1307.2023.04.014.

HUANG Li-xia,LI xin,ZHANG Shu,et al.Mechanism of Astragaloside IV on diabetic nephropathy induced by Streptozotocin in rats[J]. Beijing Journal of Traditional Chinese Medicine,2023,42(04):403-407. DOI： 10.16025/j.1674-1307.2023.04.014.

摘要

目的

探讨黄芪甲苷（AS-IV）对链脲佐菌素（STZ）诱导糖尿病肾病（DN）大鼠的作用机制。

方法

选择SPF级雄性6周龄SD大鼠30只，随机取6只大鼠作为对照组，剩余24只大鼠按65 mg/kg腹腔注射STZ（溶于0.1 mol／L柠檬酸缓冲液，pH 4.4）制备DN模型，对照组腹腔注射等体积0.1 mol/L柠檬酸缓冲液，将模型大鼠随机分为模型组、AS-IV组、胰岛素（INS）组、AS-IV+INS组各6只，分别给予AS-IV 10 mg/kg、INS 5 U、AS-IV 10 mg/kg+INS 5 U灌胃，对照组和模型组灌胃等体积1%羧甲基纤维素钠溶液，1次/d，干预8周。对比各组血糖、体质量、尿蛋白、BUN、Scr、HbA

c，血清和肾组织一氧化氮（NO）水平，肾组织中内皮型一氧化氮合酶（eNOS）、磷酸化一氧化氮合成酶丝氨酸1177位点［p-eNOS（Ser1177）］和苏氨酸495位点［p-eNOS（Thr495）］蛋白表达。

结果

与对照组比较，模型组血糖均升高（

0.05）；AS-IV组、INS组、AS-IV+INS组从第8周开始血糖值均低于模型组（

0.05）；但AS-IV组、INS组、AS-IV+INS组间血糖比较差异无统计学意义（

0.05）。与对照组比较，所有造模大鼠体质量低（

0.05），尿蛋白、BUN、Scr、HbA

c高（

0.05）；与模型组比较，AS-IV组、INS组、AS-IV+INS组体质量高（

0.05），尿蛋白、BUN、Scr、HbA

c低（

0.05）；与INS组比较，AS-IV+INS组尿蛋白、Scr低（

0.05）。与对照组比较，模型组血清和肾组织NO水平低（

0.05）；与模型组比较，AS-IV组、INS组、AS-IV+INS组血清和肾组织NO水平高（

0.05）；与INS组比较，AS-IV+INS组肾组织NO水平高（

0.05）。与对照组比较，模型组肾组织中p-eNOS（Ser1177）蛋白表达低（

0.01）；与模型组比较，AS-IV组、AS-IV+INS组肾组织中p-eNOS（Ser1177）蛋白表达高（

0.01）。

结论

黄芪甲苷可能通过eNOS/NO通路对STZ诱导DN大鼠发挥治疗，且作用位点可能在Ser1177。

Abstract

Objective

To explore the protective mechanism of astragaloside Ⅳ （AS-IV） through endothelial nitric oxide synthase （eNOS）/nitric oxide（NO） pathway in kidney of diabetic rats.

Methods

Thirty SPF male SD rats aged 6 weeks were selected. Except of the control group（n=6）， the remaining 24 rats were intraperitoneally injected with 65 mg/kg STZ （dissolved in 0.1 mol/L citric acid buffer， pH 4.4） to make DN model， while the control group was intraperitoneally injected with the same volume of 0.1 mol/L citric acid buffer. The model rats were randomly divided into model group， AS-IV group， insulin （INS） group and AS-IV+INS group with 6 rats in each group. AS-IV 10 mg/kg， INS 5 U and AS-IV 10 mg/kg+INS 5 U were given by gavage respectively， and the control group and the model group were given the same volume of 1% sodium carboxymethyl cellulose solution once a day for 8 weeks. The blood sugar， body weight， urine protein， BUN， Scr， HbA

c， nitric oxide （NO） levels in serum and kidney， and the sites of endothelial nitric oxide synthase （eNOS）， phosphorylated nitric oxide synthase serine 1 177 ［P-Enos （SER 1 177）］ and threonine 495 ［P-Enos （THR 495）］ in kidney were compared.

Results

Compared with the control group， the blood sugar in the model group was increased （

0.05）. The blood sugar levels in As-ⅳ group， INS group and As-ⅳ+INS group were lower than those in the model group from the 8th week （

0.05）. However， there was no significant difference in blood glucose among As-ⅳ group， INS group and As-ⅳ+INS group （

0.05）. Compared with the control group， the body weight of the model group was lower （

0.05）， and the urine protein， BUN， Scr and HbA

c were higher （

0.05）. Compared with the model group， AS-IV group， INS group and AS-IV+INS group had higher body mass （

0.05）， but lower urine protein， BUN， Scr and HbA

c （

0.05）. Compared with INS group， urinary protein and Scr in AS-ⅳ+INS group were lower （

0.05）. Compared with the control group， the level of NO in serum and kidney tissue in the model group was lower （

0.05）. Compared with the model group， AS-IV group， INS group and AS-IV+INS group had higher levels of NO in serum and kidney tissue （

0.05）. Compared with INS group， the level of NO in renal tissue in AS-ⅳ+INS group was higher （

0.05）. Compared with the control group， the expression of p-eNOS（Ser1177） protein in renal tissue of model group was lower （

0.01）. Compared with the model group， the expression of p-eNOS（Ser1177） protein in renal tissue of As-ⅳ group and As-ⅳ+INS group was higher （

0.01）.

Conclusion

Astragaloside IV may play a role in treating STZ-induced DN rats through eNOS/NO pathway， and the site of action may be Ser1177.

关键词

糖尿病肾病黄芪甲苷eNOS/NO通路大鼠

Keywords

Diabetic nephropathyAS-IVeNOS/NO passwayrat

references

SAMSU N. Diabetic nephropathy: challenges in pathogenesis, diagnosis, and treatment[J]. Biomed Res Int,2021:1497449.

WATANABE T, KANOME T, MIYAZAKI A, et al. Human urotensin II as a link between hypertension and coronary artery disease[J]. Hypertens Res,2006,29(6):375-387.

MAGUIRE JJ, DAVENPORT AP. Is urotensin-II the new endothelin[J]. Br J Pharmacol,2002,137(5):579-588.

KHAZIM K, GORIN Y, CAVAGLIERI RC, et al. The antioxidant silybin prevents high glucose-induced oxidative stress and podocyte injury in vitro and in vivo[J]. Am J Physiol Renal Physiol,2013,305(5):F691-700.

DUNI A, LIAKOPOULOS V, ROUMELIOTIS S, et al. Oxidative stress in the pathogenesis and evolution of chronic kidney disease: Untangling Ariadne's thread[J]. Int J Mol Sci,2019,20(15):3711.

LI L, HOU X, XU R, et al. Research review on the pharmacological effects of astragaloside IV[J]. Fundam Clin Pharmacol,2017,31(1):17-36.

LEI X, ZHANG L, LI Z, et al. Astragaloside IV/lncRNA-TUG1/TRAF5 signaling pathway participates in podocyte apoptosis of diabetic nephropathy rats[J]. Drug Des Devel Ther,2018,12:2785-2793.

NAIR AB, JACOB S. A simple practice guide for dose conversion between animals and human[J]. J Basic Clin Pharm,2016,7(2):27-31.

WANG X, LI C, HUAN Y, et al. Diphenyl diselenide ameliorates diabetic nephropathy in streptozotocin-induced diabetic rats via suppressing oxidative stress and inflammation[J]. Chem Biol Interact,2021,338:109427.

GAO Z, ZHONG X, TAN YX, et al. Apelin‑13 alleviates diabetic nephropathy by enhancing nitric oxide production and suppressing kidney tissue fibrosis[J]. Int J Mol Med,2021,48(3):175.

国家药典委员会. 中华人民共和国药典-三部（2010年版）[M].北京:中国医药科技出版社,2010:283.

李娜,于萍,周菲菲,等.黄芪甲苷对家兔子宫内膜炎模型治疗效果的评估[J].北京中医药,2019,38(10):1004-1006.

YANG B, XIAO B, SUN T. Antitumor and immunomodulatory activity of Astragalus membranaceus polysaccharides in H22 tumor-bearing mice[J]. Int J Biol Macromol,2013,62:287-290.

PAPADOPOULOU-MARKETOU N, CHROUSOS GP, KANAKA-GANTENBEIN C. Diabetic nephropathy in type 1 diabetes: a review of early natural history, pathogenesis, and diagnosis[J]. Diabetes Metab Res Rev,2017,33(2).doi: 10.1002/dmrr.2841http://dx.doi.org/10.1002/dmrr.2841.

AHMAD A， DEMPSEY SK， DANEVA Z， et al. Role of nitric oxide in the cardiovascular and renal systems［J］. Int J Mol Sci，2018，19（9）：2605.

KAN QM, HU YH, HE ZG. Normalization of the ratio of nitric oxide and peroxynitrite by promoting eNOS dimer activity is a new direction for diabetic nephropathy treatment[J]. Sheng Li Xue Bao,2022,74(1):93-109.

BRAAM B, VERHAAR MC. Understanding eNOS for pharmacological modulation of endothelial function: a translational view[J]. Curr Pharm Des,2007,13(17):1727-1740.

MOUNT PF, KEMP BE, POWER DA. Regulation of endothelial and myocardial NO synthesis by multi-site eNOS phosphorylation[J]. J Mol Cell Cardiol,2007,42(2):271-279.

GODO S, SHIMOKAWA H. Divergent roles of endothelial nitric oxide synthases system in maintaining cardiovascular homeostasis[J]. Free Radic Biol Med,2017,109:4-10.

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