Tanshinone IIA alleviates lipopolysaccharide-induced acute lung injury by downregulating TRPM7 and pro-inflammatory factors

J Cell Mol Med. 2018 Jan;22(1):646-654. doi: 10.1111/jcmm.13350. Epub 2017 Oct 18.

Abstract

The study aimed to investigate the role of Tanshinone IIA (Tan IIA) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in its regulation of TRPM7. Wistar male rats were randomly divided into the normal saline (NS), LPS, knockout (KO) + LPS, low-dose Tan IIA (Tan-L), middle-dose Tan IIA (Tan-M), high-dose Tan IIA (Tan-H) and KO + high-dose Tan IIA (KO + Tan-H) groups. The level of tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, TRPM7 protein expression, current density-voltage curve and Ca2+ concentration were detected through ELISA, Western blotting, electrophysiological experiment and a calcium-imaging technique, respectively. The rats in the KO + LPS, Tan-L, Tan-M, Tan-H and KO + Tan-H groups all displayed lower levels of TNF-α, IL-1β and IL-6 than the LPS group. Rats in the KO + Tan-H group exhibited lower levels of NF-α, IL-1β and IL-6 than rats in the Tan-H group. Elevated levels of TRPM7 protein expression in the LPS and Tan groups were detected in comparison with the NS group. However, TRPM7 protein expression in Tan-M and Tan-H groups was notably lower than in that of the LPS group. In comparison with the NS group, the LPS and Tan groups had a greater PIMs cell density and a higher concentration of Ca2+ . Contrary results were observed in the KO + LPS, Tan-H and KO + Tan-H groups. Tan IIA decreases calcium influx in PIMs and inhibits pro-inflammatory factors which provide an alleviatory effect in regards to LPS-induced ALI by suppressing TRPM7 expression.

Keywords: Tanshinone IIA; acute lung injury; interleukin 6; lipopolysaccharide; transient receptor potential melastatin 7; tumour necrosis factor alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes / pharmacology
  • Abietanes / therapeutic use*
  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / metabolism*
  • Acute Lung Injury / pathology
  • Animals
  • Calcium / metabolism
  • Down-Regulation*
  • Inflammation Mediators / metabolism*
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Lipopolysaccharides
  • Lung / drug effects
  • Lung / pathology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Organ Size
  • Oxygen / metabolism
  • Partial Pressure
  • Rats, Wistar
  • Serous Membrane / pathology
  • TRPM Cation Channels / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Abietanes
  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • TRPM Cation Channels
  • Tumor Necrosis Factor-alpha
  • tanshinone
  • Trpm7 protein, rat
  • Oxygen
  • Calcium