Abstract

Background Tanshinone IIA sodium sulfonate (TSS) is known to possess anti-inflammatory effects and has exhibited protective effects in various inflammatory conditions; however, its role in lipopolysaccharide- (LPS-) induced intestinal injury is still unknown. Objective The present study is designed to explore the role and possible mechanism of TSS in LPS-induced intestinal injury. Methods Male C57BL/6J mice, challenged with intraperitoneal LPS injection, were treated with or without TSS 0.5 h prior to LPS exposure. At 1, 6, and 12 h after LPS injection, mice were sacrificed, and the small intestine was excised. The intestinal tissue injury was analyzed by HE staining. Inflammatory factors (TNF-α, IL-1β, and IL-6) in the intestinal tissue were examined by ELISA and RT-PCR. In addition, expressions of autophagy markers (microtubule-associated light chain 3 (LC3) and Beclin-1) were detected by western blot and RT-PCR. A number of autophagosomes were also observed under electron microscopy. Results TSS treatment significantly attenuated small intestinal epithelium injury induced by LPS. LPS-induced release of inflammatory mediators, including TNF-α, IL-1β, and IL-6, were markedly inhibited by TSS. Furthermore, TSS treatment could effectively upregulate LPS-induced decrease of autophagy levels, as evidenced by the increased expression of LC3 and Beclin-1, and more autophagosomes. Conclusion The protective effect of TSS on LPS-induced small intestinal injury may be attributed to the inhibition of inflammatory factors and promotion of autophagy levels. The present study may provide novel insight into the molecular mechanisms of TSS on the treatment of intestinal injury.

Highlights

  • Sepsis is a complicated clinical syndrome mainly due to a harmful host inflammatory response to infection

  • Enzyme-linked immunosorbent assay (ELISA) kits for tumor necrosis factor-α (TNF-α), IL-6, and IL-1β were obtained from R&D Systems (Minneapolis, MN, USA)

  • Histological analysis showed the jejunum and ileum from control mice had the normal architecture of the intestinal epithelium and wall (Figures 2(a) and 2(h)), while LPS induced severe edema and sloughing of the villus tips, as well as infiltration of inflammatory cells into the mucosa at all observed time points (Figures 2(b)–2(d), 2(i)–2(k))

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Summary

Introduction

Sepsis is a complicated clinical syndrome mainly due to a harmful host inflammatory response to infection. It is still necessary to discover novel therapy for the clinical patients in response to increased bacterial infection and sepsis. The present study is designed to explore the role and possible mechanism of TSS in LPS-induced intestinal injury. TSS treatment significantly attenuated small intestinal epithelium injury induced by LPS. LPS-induced release of inflammatory mediators, including TNF-α, IL-1β, and IL-6, were markedly inhibited by TSS. TSS treatment could effectively upregulate LPS-induced decrease of autophagy levels, as evidenced by the increased expression of LC3 and Beclin-1, and more autophagosomes. The protective effect of TSS on LPS-induced small intestinal injury may be attributed to the inhibition of inflammatory factors and promotion of autophagy levels. The present study may provide novel insight into the molecular mechanisms of TSS on the treatment of intestinal injury

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