Sodium Tanshinone IIA Sulfonate Ameliorates Injury-Induced Oxidative Stress and Intervertebral Disc Degeneration in Rats by Inhibiting p38 MAPK Signaling Pathway.

Shouqian Dai,Huilin Yang,Feng Xu,Rongqing Qin,Xiu Shi,Xing Zhang,Wenyuan Ding

doi:10.1155/2021/5556122

Abstract

Objective Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, a representative traditional Chinese medicine. The aim of the study was to investigate the capability of STS to reverse injury-induced intervertebral disc degeneration (IDD) and explore the potential mechanisms. Methods Forty adult rats were randomly allocated into groups (control, IDD, STS10, and STS20). An IDD model was established by puncturing the Co8-9 disc using a needle. Rats in the STS groups were administered STS by daily intraperitoneal injection (10 or 20 mg/kg body weight) while rats in the control and IDD groups received the same quantity of normal saline. After four weeks, the entire spine from each rat was scanned for X-ray and MRI analysis. Each Co8-9 IVD underwent histological analysis (H&E, Safranin-O Fast green, and alcian blue staining). A tissue was analyzed by immunohistochemical (IHC) staining to determine the expression levels of collagen II (COL2), aggrecan, matrix metalloproteinase-3/13 (MMP-3/13), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Levels of oxidative stress were measured using an ELISA while activity of the p38 MAPK pathway was assessed using Western blot analysis. Results Compared with the control group, needle puncture significantly decreased IVD volume and T-2 weighted MR signal intensity, confirming disc degeneration. These alterations were significantly attenuated by treatment with 10 or 20 mg/kg STS. Lower COL2 and aggrecan and higher MMP-3/13, IL-1β, IL-6, and TNF-α levels in the IDD group were substantially reversed by STS. In addition, treatment with STS increased antioxidative enzyme activity and decreased levels of oxidative stress induced by needle puncture. Furthermore, STS inhibited the p38 MAPK pathway in the rat model of IDD. Conclusions STS ameliorated injury-induced intervertebral disc degeneration and displayed anti-inflammatory and antioxidative properties in a rat model of IDD, possibly via inhibition of the p38 MAPK signaling pathway.

Highlights

Intervertebral disc degeneration (IDD) is recognized as among the most common causes of lower back pain [1]
A previous research study demonstrated that oxidative stress at least partly leading to the structural failure of degenerated intervertebral discs (IVDs) results from the excessive production of reactive oxygen species (ROS) [13]
Five μm serial sections were obtained from the midsagittal region and stained with hematoxylin and eosin (H&E), Safranin-O Fast green, and alcian blue in order that histological changes in the IVDs could be identified and assessed using a previously described scale, providing scores from 5 to 15 points, representing IVDs that were normal to severely degenerated [26]

Summary

Objective

Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, a representative traditional Chinese medicine. Compared with the control group, needle puncture significantly decreased IVD volume and T-2 weighted MR signal intensity, confirming disc degeneration. These alterations were significantly attenuated by treatment with 10 or 20 mg/kg STS. Lower COL2 and aggrecan and higher MMP-3/13, IL-1β, IL-6, and TNF-α levels in the IDD group were substantially reversed by STS. Treatment with STS increased antioxidative enzyme activity and decreased levels of oxidative stress induced by needle puncture. STS inhibited the p38 MAPK pathway in the rat model of IDD. STS ameliorated injury-induced intervertebral disc degeneration and displayed anti-inflammatory and antioxidative properties in a rat model of IDD, possibly via inhibition of the p38 MAPK signaling pathway

Introduction

Materials and Methods

Results

Discussion