Acute lung injury (ALI) is a respiratory disorder characterized by severe
inflammation of the alveoli and lung parenchyma.
Tetramethylpyrazine (
TMP), the main active compound in Ligusticum chuanxiong Hort (LC), can protect against
lipopolysaccharide (LPS)-induced ALI. Our study aimed to investigate how
TMP protects the endothelial cell barrier in pulmonary capillaries. We administered
TMP intraperitoneally at different doses and found that
acute lung injury in mice was improved, but not in a dose-dependent manner.
TMP toxicity was tested in vitro. We observed that LPS-induced cytoskeletal remodeling was inhibited by
TMP. Murine ALI was induced as follows: For the 1st hit, LPS (2 mg/kg) was injected intraperitoneally; after 16 h, for the 2nd hit, LPS (4 mg/kg) was instilled intratracheally. The mice in treatment groups had
TMP or
dexamethasone administered intraperitoneally 30 min prior to the 1st hit and 30 min past the 2nd hit. Mice were euthanized 24 h after the last injecting. We measured
protein and
mRNA levels using
enzyme-linked
immunosorbent assay (ELISA) and
reverse transcriptase real-time PCR (RT-qPCR), respectively. The ultrastructural analysis was performed with transmission electron microscopy (TEM) and the cytoskeleton was observed by immunofluorescence. Immunohistochemistry and Western blotting were used to detect
protein expression in the Rac1/LIMK1/ZO-1/
occludin signal pathway. The results showed that
TMP treatment decreased inflammatory cell infiltration and alleviated LPS-induced damage in lung tissue. Also,
TMP significantly inhibited the Rac1/LIMK1/ZO-1/
occludin signaling pathway. Our findings show that using
TMP during
sepsis can protect the pulmonary microvascular endothelial cell barrier and suppress
inflammation. Therefore,
TMP may have a promising therapeutic role in preventing
acute lung injury from
sepsis.