[Frontiers in Bioscience E4, 1303-1313, January 1, 2012]

Tanshinone IIA pretreatment attenuates hepatic ischemia-reperfusion

Yan-yan Qi1, Liang Xiao2, Lu-ding Zhang2, Shao-hua Song2, Yi Mei1, Teng Chen1, Jian-ming Tang1, Fang Liu2, Guo-shan Ding2, Yong-zhao Shi1, Quan-xing Wang3

1Department of General Surgery, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China, 2Department of Organ Transplantation, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China, 3National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, China


1. Abstract
2. Introduction
3. Materials and Methods
3.1. Animals and reagents
3.2. Experimental groups and mouse hepatic I/R injury model
3.3. Serum aminotransferases assay and histopathological assessment
3.4. Serum proinflammatory cytokine assay
3.5. Immunohistochemistric analysis of inflammatory infiltration
3.6. Preparation of mouse hepatic parenchymal cells and nonparenchymal cells
3.7. Real-time polymerase chain reaction (RT-PCR)
3.8. Western blot analysis
3.9. Statistical analysis
4. Results
4.1. Tan IIA attenuated hepatic I/R injury
4.2. Tan IIA inhibited proinflammatory cytokine production
4.3. Tan IIA inhibited leukocyte infiltration in the liver
4.4. Tan IIA regulated the axis for TLR4 signaling and HO-1 expression in the liver
4.5. Tan IIA triggered the protective signaling pathways in the liver
5. Discussion
6. Acknowledgement
7. References


Tanshinone IIA (Tan IIA), an active component derived from Salvia miltiorrhiza root, has been used to treat various ischemic cardiovascular and cerebrovascular diseases. However, its impact on hepatic ischemia/reperfusion (I/R) injury remains unclear. Here, we addressed this issue by using a 90-minute partial liver ischemia model. Mice were administered Tan IIA intragastrically for 3 days before ischemia and were assessed for liver damage 6-h after reperfusion. Tan IIA pretreatment significantly inhibited serum aminotransferases and proinflammatory cytokine levels along with reduced inflammatory infiltration and liver damage. Mechanistic studies revealed that Tan IIA suppressed TLR4 expression in nonparenchymal cells (NPCs) and induced heme oxygenase-1 (HO-1) production in both parenchymal and NPCs. Moreover, the phosphorylation of AKT and ERK1/2 in the liver was enhanced, while the phosphorylation of JNK, p38 and p65 was suppressed. These results suggest Tan IIA can suppress TLR4 signaling which then enhances HO-1 expression along with reduced proinflammatory cytokine expressions in the liver, and Tan IIA could be a useful candidate drug in clinic for prevention and treatment of hepatic I/R injury.