Study on the protective mechanism of anti-platelet thrombolysin against cerebral ischemia reperfusion injury in rats

doi:10.12092/j.issn.1009-2501.2018.10.005

Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2018, Vol. 23 ›› Issue (10): 1109-1115.doi: 10.12092/j.issn.1009-2501.2018.10.005

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Study on the protective mechanism of anti-platelet thrombolysin against cerebral ischemia reperfusion injury in rats

LUO Shengyong¹, JIA Dewu ², LI Xiaoyi ³, DAI Xiangrong ³

¹ Anhui Provincial Institute of Medical Science, Hefei 230061, Anhui, China; ²Affiliated High-tech Hospital of Anhui Medical University, Hefei 230032, Anhui, China; ³Zhaoke Pharmaceutical(Hefei) Company Limited, Hefei 230088, Anhui, China

Received:2018-07-05 Revised:2018-09-11 Online:2018-10-26 Published:2018-10-25

Abstract

Abstract:

AIM: To investigate the protective mechanism of anti-platelet thrombolysin (APT) on cerebral ischemia reperfusion injury in rats. METHODS: The TLR4 siRNA in vivo transfection technique was used to reduce the TLR4 expression in the brain of rat. Wild-type and TLR4 down-regulated rats were randomly divided into six groups: sham group, model group, TAK-242 (Toll-like receprot 4 blocker) 2 mg/kg group, APT 0.02 mg/kg, 0.01 mg/kg, 0.005 mg/kg group respectively with eight rats in each group. The rat focal ischemia-reperfusion injury model was established by ligation of middle cerebral artery occlusion(MCAO). RhoA activity was measured using absorbance based G-LISA RhoA activation assay and the expression of TLR4, ROCK1/2 and p-JNK were determined by Western blot. RESULTS: The expression of TLR4 protein in TLR4 siRNA transfected rats brain tissue decreased significantly compared with that in control group rats. Compared with model group, APT could obviously decrease the TLR4, ROCK1/2 and p-JNK protein expression, inhibit the RhoA activity in wild rat brain; however, APT had no significant effect on RhoA activity, ROCK1/2 and p-JNK protein expression in brain compared with model group in TLR4 siRNA transfected rats. CONCLUSION: The protective mechanism of APT on cerebral ischemia reperfusion injury in rats is mainly related to the inhibition of TLR4/RhoA/ROCK signaling pathway.

Key words: anti-platelet thrombolysin, siRNA transfection in vivo, toll like receptor 4, RhoA/ROCK signaling pathway

CLC Number:

R965.2

LUO Shengyong, JIA Dewu, LI Xiaoyi, DAI Xiangrong. Study on the protective mechanism of anti-platelet thrombolysin against cerebral ischemia reperfusion injury in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(10): 1109-1115.

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Study on the protective mechanism of anti-platelet thrombolysin against cerebral ischemia reperfusion injury in rats

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