Atorvastatin attenuates experimental contrast-induced acute kidney injury: a role for TLR4/MyD88 signaling pathway

Rongzheng Yue; Chuan Zuo; Jing Zeng; Baihai Su; Ye Tao; Songmin Huang; Rui Zeng

doi:10.1080/0886022X.2017.1361838

Atorvastatin attenuates experimental contrast-induced acute kidney injury: a role for TLR4/MyD88 signaling pathway

Ren Fail. 2017 Nov;39(1):643-651. doi: 10.1080/0886022X.2017.1361838.

Authors

Rongzheng Yue¹, Chuan Zuo², Jing Zeng³, Baihai Su¹, Ye Tao¹, Songmin Huang¹, Rui Zeng⁴

Affiliations

¹ a Department of Nephrology , West China Hospital, School of Clinic Medicine, Sichuan University , Chengdu , PR China.
² b Department of Rheumatology and Immunology , West China Hospital, School of Clinic Medicine, Sichuan University , Chengdu , PR China.
³ c Department of Internal Medicine , West China Hospital, School of Clinic Medicine, Sichuan University , Chengdu , PR China.
⁴ d Department of Cardiovascular Diseases , West China Hospital, School of Clinic Medicine, Sichuan University , Chengdu , PR China.

Abstract

Objectives: To investigate the protective effect of different atorvastatin doses on contrast-induced acute kidney injury and the related mechanism.

Methods: Healthy male Sprague-Dawley (SD) rats were randomly divided into the blank control group, experimental control group and different-dose atorvastatin groups. A rat model of contrast-induced acute kidney injury was established. We detected changes in serum creatinine (Scr) and blood urea nitrogen (BUN) before and after model establishment, observed and scored renal tubular injury, analyzed rat renal cell apoptosis, and measure the expression of signal pathway proteins and downstream inflammatory factors.

Results: After contrast agent injection, the Scr and BUN levels of the experimental control group were significantly increased, the different doses applied in the atorvastatin group significantly reduced the Scr and BUN levels (p < .05) and ameliorated the contrast-induced acute kidney injury (p < .05) and significantly reduced Toll-like receptor 4 (TLR4), Myeloid differentiation factor 88 (Myd88), and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) protein expression and relative mRNA expression levels (p < .05) and significantly decreased expression levels of downstream inflammatory factors (p < .05).

Conclusion: Different atorvastatin doses have protective effects on contrast-induced acute renal tubular injury in rats, possibly by targeting TLR4, suppressing TLR4 expression, regulating the TLR4/Myd88 signaling pathway, and inhibiting the expression of downstream inflammatory factors.

Keywords: Contrast-induced acute kidney injury; TLR4/MyD88; atorvastatin; renal failure; signaling pathway.

MeSH terms

Acute Kidney Injury / blood
Acute Kidney Injury / chemically induced
Acute Kidney Injury / prevention & control*
Animals
Atorvastatin / pharmacology
Atorvastatin / therapeutic use
Blood Urea Nitrogen
Contrast Media / adverse effects*
Creatinine / blood
Disease Models, Animal
Dose-Response Relationship, Drug
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
Kidney Function Tests
Kidney Tubules / drug effects
Kidney Tubules / pathology
Male
Myeloid Differentiation Factor 88 / metabolism*
NF-kappa B / metabolism
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Signal Transduction / drug effects*
Toll-Like Receptor 4 / metabolism*

Substances

Contrast Media
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Myd88 protein, rat
Myeloid Differentiation Factor 88
NF-kappa B
RNA, Messenger
Tlr4 protein, rat
Toll-Like Receptor 4
Atorvastatin
Creatinine

Grants and funding

This work was supported financially by grants from National Natural Science Foundation of China [No. 81200153], Science Foundation of Science and Technology Department, Sichuan Province [No.2015SZ0180, 2015SZ0192, 2015SZ0148 and 2014JY0204].