Tao Shang1, Feng Ran1, Qian Qiao2, Zhao Liu1, Chang-Jian Liu1. 1. Department of Vascular Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China. 2. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
Abstract
BACKGROUND: The purpose of this study was to determine whether myeloid differentiation factor88-dependent Toll-Like Receptor-4 (TLR-4) signaling contributed to the inhibition of abdominal aortic aneurysm (AAA) by Tanshinone IIA (Tan IIA). MATERIALS AND METHODS: Male Sprague-Dawley rats (n = 12 / group) were randomly distributed into three groups: Tan IIA, control, and sham. The rats from Tan IIA and control groups under-went intra-aortic elastase perfusion to induce AAAs, and those in the sham group were perfused with saline. Only the Tan IIA group received Tan IIA (2 mg / rat / d). Aortic tissue samples were harvested at 24 d after perfusion and evaluated using reverse transcriptase-polymerase chain reaction, Western blot, immunohistochemistry and immunofluorescence. RESULTS: The over-expression of Toll-Like Receptor-4 (TLR-4), Myeloid Differentiation factor 88 (MyD88), Phosphorylated Nuclear Factor κB (pNF-κB) and Phosphorylated IκBα (pIκBα) induced by elastase perfusion were significantly decreased by Tan IIA treatment. CONCLUSIONS: Tan IIA attenuates elastase-induced AAA in rats possibly via the inhibition of MyD88-dependent TLR-4 signaling, which may be one potential explanation of why Tan IIA inhibits AAA development through multiple effects.
BACKGROUND: The purpose of this study was to determine whether myeloid differentiation factor88-dependent Toll-Like Receptor-4 (TLR-4) signaling contributed to the inhibition of abdominal aortic aneurysm (AAA) by Tanshinone IIA (Tan IIA). MATERIALS AND METHODS: Male Sprague-Dawley rats (n = 12 / group) were randomly distributed into three groups: Tan IIA, control, and sham. The rats from Tan IIA and control groups under-went intra-aortic elastase perfusion to induce AAAs, and those in the sham group were perfused with saline. Only the Tan IIA group received Tan IIA (2 mg / rat / d). Aortic tissue samples were harvested at 24 d after perfusion and evaluated using reverse transcriptase-polymerase chain reaction, Western blot, immunohistochemistry and immunofluorescence. RESULTS: The over-expression of Toll-Like Receptor-4 (TLR-4), Myeloid Differentiation factor 88 (MyD88), Phosphorylated Nuclear Factor κB (pNF-κB) and Phosphorylated IκBα (pIκBα) induced by elastase perfusion were significantly decreased by Tan IIA treatment. CONCLUSIONS: Tan IIA attenuates elastase-induced AAA in rats possibly via the inhibition of MyD88-dependent TLR-4 signaling, which may be one potential explanation of why Tan IIA inhibits AAA development through multiple effects.
Authors: Y W Yin; S Q Liao; M J Zhang; Y Liu; B H Li; Y Zhou; L Chen; C Y Gao; J C Li; L L Zhang Journal: Cell Death Dis Date: 2014-12-18 Impact factor: 8.469