Effect of tripterygium wilfordii polyglycoside on renal cell autophagy in rats with diabetic nephropathy and its related mechanism

ZHANG Jun DING Ting TANG Dong-xing WANG Jian-ping

Acta Anatomica Sinica ›› 2020, Vol. 51 ›› Issue (3) : 373-377.

PDF(982 KB)
Welcome to visit Acta Anatomica Sinica! Today is Chinese
PDF(982 KB)
Acta Anatomica Sinica ›› 2020, Vol. 51 ›› Issue (3) : 373-377. DOI: 10.16098/j.issn.0529-1356.2020.03.010
Cell and Molecules Biology

Effect of tripterygium wilfordii polyglycoside on renal cell autophagy in rats with diabetic nephropathy and its related mechanism

  •  ZHANG Jun1 DING Ting1 TANG Dong-xing1 WANG Jian-ping2*
Author information +
History +

Abstract

Objective  To investigate the effects of tripterygium glycosides on autophagy of renal cells in rats with diabetic nephropathy and to analyze its molecular mechanism.   Methods  A rat model of diabetic nephropathy was made by intraperitoneal injection of streptavidin. Thirty SD rats were randomly divided into 5 groups, control group, model group, 0.1 mg/kg drug group, 0.5 mg/kg drug group and 1.0 mg/kg drug group, and each group has 6 rat. After the successful establishment of the diabetic nephropathy model, the 0.1 mg/kg drug group, the 0.5 mg/kg drug group, and the 1.0 mg/kg drug group were intragastric administration with 0.1, 0.5, and 1.0 mg/kg tripterygium glycosides, respectively, and the control group and the model group were intraperitoneally injected with the same amount of normal saline. The levels of renal function and oxidative stress were compared among groups. The expression levels of p-mammalian target of rapamycin (p-mTOR),mammalian target of rapamycin(mTOR), microtubules associated protein 1 light chain 3β-Ⅱ/microtubules associated protein 1 light chain 3β-Ⅰ(LC3-Ⅱ/LC3-Ⅰ) and Beclin1 protein were detected by Western blotting. The expression levels of  LC3, LC3-Ⅱ and Beclin1 mRNA in each group were detected by Real-time PCR.   Results  Compared with the control group, the serum creatinine(Scr), blood urea nitrogen(BUN), protein(Pro) and malondialdehyde(MDA) levels in the model group increased,and the the glutathione peroxidase(GSH-Px) and catalase(CAT) levels decreased significantly (P<0.05). Compared with the model group, the Scr, BUN, Pro and MDA levels of the drug group were significantly decreased, and GSH-Px and CAT levels were significantly increased in a dose-dependent manner (P<0.05). Compared with the control group, the expression level of p-mTOR protein in the renal tissue of the model group was increased, and the expression levels of LC3-Ⅱ/LC3-Ⅰ and Beclin1 protein were decreased (P<0.05). Compared with the model group, the expression level of p-mTOR protein was decreased in the dose group, and the expression levels of LC3-Ⅱ/LC3-Ⅰ protein in the dose group were significantly increased in a dose-dependent manner (P<0.05). The expression levels of Beclin1 protein in the 0.5 mg/kg drug group and 1.0 mg/kg drug group, were  significantly higher than the model group (P<0.05). Compared with the control group, the expression levels of LC3-Ⅱ/LC3-Ⅰ and Beclin1 mRNA in the renal tissue of the model group were significantly lower (P<0.05). Compared with the model group, the expression levels of LC3 and Beclin1 mRNA in the drug groups of each dose group were significantly increased (P<0.05).   Conclusion  Tripterygium wilfordii glycosides can protect kidney function in rats with diabetic nephropathy, and its mechanism might be related to inhibition of oxidative stress and activation of autophagy.

Key words

Tripterygium glycoside / Diabetic nephropathy / Autophagy / Western blotting / Rat

Cite this article

Download Citations
ZHANG Jun DING Ting TANG Dong-xing WANG Jian-ping. Effect of tripterygium wilfordii polyglycoside on renal cell autophagy in rats with diabetic nephropathy and its related mechanism[J]. Acta Anatomica Sinica. 2020, 51(3): 373-377 https://doi.org/10.16098/j.issn.0529-1356.2020.03.010

References

[1] Chen WD, Zhang JQ, Zhang Y, et al.Efficacy of glucosidorum tripterygll totorum combined with ambrette capsules in treatment of diabetic nephropathy and its effect on inflammatory factors[J]. Chinese Journal of Clinical Pharmacology, 2015, 31 (12): 1157-1161. (in Chinese)
陈卫东, 张继强, 张燕, 等. 雷公藤多苷对糖尿病肾病大鼠肾基质金属蛋白酶-9和基质金属蛋白酶抑制剂-1表达的影响[J]. 中国临床药理学杂志, 2015,31(12):1157-1161.
[2] Tsai SF, Su CW, Wu MJ, et al. Urinary cyclophilin a as a new marker for diabetic nephropathy[J]. Medicine, 2015, 94(42):e1802.
[3] Zhang LM, Li HY, Gao Y, et al. Protective effects and possible mechanisms of tripterygium wilfordii polyglycosides on renal injury in diabetic nephropathy rats [J].Chinese Journal of Gerontology, 2016, 36 (14): 3389-3391.  (in Chinese)
张丽敏, 李鸿燕, 高燕, 等. 雷公藤多苷对糖尿病肾病大鼠肾损伤的保护作用及可能机制[J]. 中国老年学杂志, 2016, 36(14):3389-3391.
[4] Zhang YX, Liu GL, Wang JQ, et al. Antioxidative stress effects of tripterygium wilfordii polyglycosides on diabetic nephropathy rats [J]. Chinese Journal of Pharmacology and Toxicology, 2014, 28 (3): 358-361. (in Chinese)
张玉霞,刘国玲,王家勤,等.雷公藤多苷对糖尿病肾病大鼠的抗氧化应激作用[J].中国药理学与毒理学杂志,2014,28(3):358-361.
[5] Li ChH, Zhang Y, Li KX, et al. Resveratrol protects renal function in diabetic nephropathy rats by inducing autophagy [J].Chinese Journal of Laboratory Diagnosis, 2014, 18 (12): 1920-1922. (in Chinese)
李春花,张英,李可心,等.白藜芦醇通过诱导自噬保护糖尿病肾病大鼠肾功能的研究[J].中国实验诊断学,2014,18(12):1920-1922.
[6] Shi G, Shi Y, Sun XB, et al. Establishing methods and standard of diabetic nephropathy rat model[J]. Journal of Liaoning University of Traditional Chinese Medicine, 2014, 16(7):171-173. (in Chinese)
石光, 石岩, 孙晓波, 等. 糖尿病肾病大鼠模型制备方法与模型建立标准研究[J]. 辽宁中医药大学学报, 2014,16(7):171-173.
[7] Wu WF, Cheng ZhQ, Shi XD. Effect of combination of tripterygium glycosides and valsartan on chronic glomerulonephritis complication with hypertension and effect on inflammatory cytokines[J].Chinese Journal of Biochemical Pharmaceutics, 2016, 36(8):101-104. (in Chinese)
吴炜飞, 程志群, 施向东. 雷公藤多苷联合缬沙坦治疗慢性肾小球肾炎合并高血压患者的临床疗效及对炎症因子的影响[J]. 中国生化药物杂志, 2016, 36(8):101-104.
[8] Zhu TF, Chu ZhF, Li JH, Effect of tripterygium glycosides and Danshen injection on blood coagulationmechanism in children with allergic purpura nephritis[J].China Journal of Chinese Materia Medica, 2016, 41 (11): 2162-2167. (in Chinese)
朱廷富, 褚祝飞, 李精华. 雷公藤多苷联合丹参注射液对过敏性紫癜性肾炎患儿凝血机制的影响[J]. 中国中药杂志, 2016, 41(11):2162-2167.
[9] Jiao AJ, Li ZhB, Li G, et al. Effect of PNS combined with TG on TNF-α, IL-6, MCP-1 levels in serum of CIA rats and thoracic aorta MCP-1 expression[J]. Modern Journal of Integrated Traditional Chinese and Western Medicine, 2016, 25(7):712-715. (in Chinese)
焦爱军, 李振彬, 李广,等. 三七总皂苷联合雷公藤多苷对关节炎大鼠外周血 TNF-α、IL-6、MCP-1以及胸主动脉MCP-1表达的影响[J]. 现代中西医结合杂志, 2016, 25(7):712-715.
[10] Chen H. Dihydromyricetin prevents against diabetic nephropathy through the activation of AMPK pathway [D]. Third Military Medical University, 2017. (in Chinese)
陈红. 二氢杨梅素激活AMPK通路预防糖尿病肾病的作用研究[D].第三军医大学,2017.
[11] Hao X, Lin B, Wang ZhZh, et al.Spectrum-effect relationship of immunosuppressive effects and toxicity of tripterygium wilfordii HooK F[J]. Chinese Journal of Hospital Pharmacy, 2016, 36(7):547-552. (in Chinese)
昊霞, 林兵, 王忠震,等. 雷公藤的免疫抑制活性及毒性的谱效关系研究[J]. 中国医院药学杂志, 2016, 36(7):547-552.
[12] Cao A, Wang L, Chen X, et al. Ursodeoxycholic acid ameliorated diabetic nephropathy by attenuating hyperglycemia-Mediated oxidative stress[J].Biol Pharm Bull, 2016, 39(8):1300-1308.
[13] Zhang JQ, Chen WD, Zhang HF, et al. Effects of different doses of Tripterygium wilfordii polyglycosides on the expression of MDA, SOD and MCP-1 in kidneys of rats with early diabetic nephropathy [J].Chinese Journal of Nephrology, 2013, 29 (7): 534-535. (in Chinese)
张继强, 陈卫东, 张海峰,等. 不同剂量雷公藤多苷对早期糖尿病肾病大鼠肾脏MDA、SOD及MCP-1表达的影响[J]. 中华肾脏病杂志, 2013, 29(7):534-535.
[14] Tagawa A, Yasuda M, Kume S, et al. Impaired podocyte autophagy exacerbates proteinuria in diabetic nephropathy[J]. Diabetes, 2016, 65(3):755-767.
[15] Wu ST, Sun GH, Cha TL, et al. CSC-3436 switched tamoxifen-induced autophagy to apoptosis through the inhibition of AMPK/mTOR pathway[J]. J Biomed Sci, 2016, 23(1):60.
[16] Nazio F, Strappazzon F, Antonioli M, et al. mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6[J]. Nature Cell Biol, 2013, 15(4):406-416.
[17] Li L, Zhao R, Li ChJ, et al. Protective effects of tripterygium wilfordii polyglycosides on kidneys of diabetic rats [J]. Chinese Journal of Diabetes, 2016, 24 (5): 459-464. (in Chinese)
厉莉, 赵然, 李春君,等. 雷公藤多苷对糖尿病大鼠肾脏的保护作用[J]. 中国糖尿病杂志, 2016, 24(5):459-464.
[18] Li L, Li R, Liu J, et al. Expression and significance of three autophagy regulator protein in parotid pleomorphic adenoma and carcinoma in pleomorphic adenoma [J].Chinese Journal of Anatomy, 2016, 39(5):549-552. (in Chinese)
李磊, 李冉, 刘江, 等 三种自噬调控蛋白在腮腺良、恶性多形性腺瘤中的表达及意义[J]. 解剖学杂志, 2016, 39(5):549-552.
[19] Kitada M, Ogura Y, Suzuki T, et al. A very-low-protein diet ameliorates advanced diabetic nephropathy through autophagy induction by suppression of the mTORC1 pathway in Wistar fatty rats, an animal model of type 2 diabetes and obesity[J]. Diabet, 2016, 59(6):1307-1317.
PDF(982 KB)

Accesses

Citation

Detail

Sections
Recommended

/