Influence of Thrombopoietin on JAK2/STAT3 Signal Transduction Pathway in Focal Cerebral Ischemia-Reperfusion Injury of Rats / 医药导报

ABSTRACT

Objective To investigate protective effects of thrombopoietin ( TPO) on cerebral model control in rats and associated signal transduction pathway. Methods Thread embolism was performed to generate cerebral ischemia-reperfusion rat model. Eighty male SD rats were randomly divided into sham operation group, model control group, TPO group, TPO and Janus kinase 2 ( JAK2 ) kinase inhibitor ( AG490 ) group. Before 30 min of ischemia-reperfusion, TPO group was given TPO (5 μg·kg-1) by intraperitoneal injection, TPO + AG490 group was given TPO (5 μg·kg-1) before 30 min of ischemia reperfusion, then given AG490 (8 μg·kg-1), and model control group were given the same dose of 0. 9% sodium chloride solution. The observation time points were 6, 12, 24, and 48 h after ischemia reperfusion. Immunohistochemical staining and Western blotting were used to measure the protein levels of Bcl-2, JAK2 and signal transducer & activator of transcription (STAT3). TdT-mediated dUTP nick end labeling (TUNEL) was used to detect apoptosis. Results Compared with model control group, the number of apoptotic cells were significantly reduced [(67. 50±9. 37) vs. (40. 20±7. 47)], the expression levels of Bcl-2, JAK2 and STAT3 protein were significantly increased [(35. 40±7. 39) vs. (78. 70±9. 75);(35. 68±6. 75) vs. (62.35±7.53); (25.40±9.45) vs.(55.36±9.69), respectively] 24 h after ischeia reperfusion in the TPO group (all P<0. 05). Compared with the TPO group, the Bcl-2, JAK2 and STAT3 protein levels were significantly decreased in TPO and AG490 group [(78. 70±9. 75) vs. (55. 40±9. 35);(62. 35±7. 53) vs. (40. 68±5. 89); (55. 36±9. 69) vs. (30. 40±9. 39), respetively], and the number of apoptotic cells was significantly increased [(40. 20±7. 47) vs. (55. 23±7. 65)] (all P<0. 05). Conclusion TPO can inhibit cell apoptosis after ischemia-reperfusion injury, the mechanism might be related to the activation of JAK2/STAT3 signal transduction pathway through raising the expression of Bcl-2 gene.