Research Paper Volume 14, Issue 20 pp 8302—8320

Renoprotective effect of Tanshinone IIA against kidney injury induced by ischemia-reperfusion in obese rats

He Tai1,2, *, , Xiao-Zheng Cui3, *, , Jia He4, *, , Zhi-Ming Lan4, *, , Shun-Min Li5, , Ling-Bing Li6, , Si-Cheng Yao7, , Xiao-Lin Jiang5,7, &, , Xian-Sheng Meng1, , Jin-Song Kuang8, ,

  • 1 School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China
  • 2 Department of Internal Medicine, Liaoning Provincial Corps Hospital of Chinese People’s Armed Police Forces, Shenyang, China
  • 3 Cardiovascular Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
  • 4 Post-Doc Mobile Station, Liaoning University of Traditional Chinese Medicine, Shenyang, China
  • 5 Nephrology Laboratory, The Fourth of Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine (Shenzhen Traditional Chinese Medicine Hospital), Guangzhou University of Traditional Chinese Medicine, Shenzhen, China
  • 6 Department of Graduate School, China PLA General Hospital, Beijing, China
  • 7 Key Laboratory of Ministry of Education for Traditional Chinese Medicine Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, China
  • 8 Department of Endocrinology and Metabolism, The Fourth People’s Hospital of Shenyang, Shenyang, China
* Equal contribution

Received: May 6, 2022       Accepted: September 12, 2022       Published: October 20, 2022
How to Cite

Copyright: © 2022 Tai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Objective: Obesity enhances the frequency and severity of acute kidney injury (AKI) induced by renal ischemia-reperfusion (IR). Tanshinone IIA (TIIA) pre-treatment was used to alleviate renal injury induced by renal IR, and whether TIIA can attenuate renal cell apoptosis via modulating mitochondrial function through PI3K/Akt/Bad pathway in obese rats was examined.

Methods: Male rates were fed a high-fat diet for 8 weeks to generate obesity, followed by 30 min of kidney ischemia and 24 h reperfusion induced AKI. The male obese rates were given TIIA (5 mg/kg.d, 10 mg/kg.d, and 20 mg/kg.d) for 2 weeks before renal IR.

Results: TIIA alleviated the pathohistological injury and apoptosis induced by IR. In addition, TIIA improved renal function, inflammatory factor, and balance of oxidation and antioxidation in obese rats after renal IR. At the same time, TIIA can inhibit cell apoptosis by improving mitochondrial function through the PI3K/Akt/Bad pathway. Mitochondrial dysfunction was supported by decreasing intracellular ATP, respiration controlling rate (RCR), mitochondrial membrane potential (MMP), and mitochondrial respiratory chain complex enzymes, and by increasing ROS, the opening of mitochondrial permeability transition pore (mPTP), and the mtDNA damage. The injury to mitochondrial dynamic function was assessed by decreasing Drp1, and increasing Mfn1/2; and the injury of mitochondrial biogenesis was assessed by decreasing PGC-1, Nrf1, and TFam.

Conclusions: Renal mitochondrial dysfunction occurs along with renal IR and can induce renal cell apoptosis. Obesity can aggravate apoptosis. TIIA can attenuate renal cell apoptosis via modulating mitochondrial function through PI3K/Akt/Bad pathway in obese rats.


IR: ischemia-reperfusion; AKI: acute kidney injury; TIIA: Tanshinone IIA; HE: hematoxylin-eosin; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling; MMP: mitochondrial membrane potential; ATP: adenosine triphosphate; ROS: reactive oxygen species; RCR: respiration controlling rate; mPTP: mitochondrial permeability transition pore; CyP-D: cyclophilin D; DMSO: dimethylsulfoxide; HFD: high-fat diet; SD: Sprague-Dawley; PBS: phosphate buffer saline; DAPI: 4':6-diamidino-2-phenylindole; RT-qPCR: Real-time Quantitative PCR; HE: hematoxylin-eosin; BCA: bicinchoninic acid; DCFH-DA: 2’:7’-Dichlorodihydrofluorescein diacetate; qPCR: quantitative Polymerase Chain Reaction; mtDNA: mitochondrial DNA; MPO: myeloperoxidase; IRI: ischemia-reperfusion injury; Tfam: mitochondrial transcription factor A; Mfn1: Mitofusin1; Mfn2: Mitofusin2; Drp1: Dynamin-related protein 1; PGC-1α: Peroxisome proliferator-activated receptor γ coactiva-tor-1; Nrf1: Nucleo-respiratory factor 1; ANOVA: analysis of variance; PI3K: Phosphoinositide-3 kinase; Cyt-c: cytochrome C; PARP: poly ADP-ribose polymerase.