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

• Published in: Journal of cellular and molecular medicine Vol. 22; no. 1; pp. 646 - 654
• Main Authors: Li, Jie, Zheng, Yan, Li, Ming‐Xian, Yang, Chu‐Wei, Liu, Yu‐Fei
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.01.2018; John Wiley and Sons Inc
• Subjects: Abietanes - pharmacology; Abietanes - therapeutic use; acute lung injury; Acute Lung Injury - chemically induced; Acute Lung Injury - drug therapy; Acute Lung Injury - metabolism; Acute Lung Injury - pathology; Animals; Calcium; Calcium - metabolism; Calcium channels (voltage-gated); Calcium imaging; Calcium influx; Cell density; Down-Regulation; Enzyme-linked immunosorbent assay; Inflammation; Inflammation Mediators - metabolism; Interleukin 1; Interleukin 6; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; lipopolysaccharide; Lipopolysaccharides; Lung - drug effects; Lung - pathology; Lungs; Macrophages - drug effects; Macrophages - metabolism; Male; Organ Size; Original; Oxygen - metabolism; Partial Pressure; Protein expression; Proteins; Rats; Rats, Wistar; Rodents; Serous Membrane - pathology; Tanshinone IIA; transient receptor potential melastatin 7; Transient receptor potential proteins; TRPM Cation Channels - metabolism; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumors; tumour necrosis factor alpha; Western blotting; Tanshinone IIA; interleukin 6; transient receptor potential melastatin 7; lipopolysaccharide; acute lung injury; tumour necrosis factor alpha
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.13350

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.