Recently, the small animal tree shrew is becoming increasingly popular, in part because of its close evolutionary relationship with primates; in part because of its unique advantages in the study of hepatitis viruses infection, myopia, depression and so on. Although non-human primates’ models can best mimic the conditions of human pathology, they are terrible models when come to economic and ethical reasons. Thus, small animal models with close evolutionary relationship to primates are of interests. Based on the backgrounds of the tree shrew and the research interests in my laboratory, we evaluated the potential advantages of tree shrew models in thrombosis and bacterial infections. Using a combination of Polymerase Chain Reaction (PCR), Western blot and flow cytometer assays, we found that the tree shrew’s platelets (Tupaia belangeri) express protease activated receptor (PAR) 1 and 4. This result reveals that the expression of PARs on the tree shrew’s platelets is similar to that of the human counterparts, but different from that of mouse platelets with PAR3 and 4. Next, we established in vitro and in vivo ferric chloride induced thrombosis models to evaluate the effects of Vorapaxar, a human platelets’ PAR1 competitive inhibitor drug in its Phase III clinical trials, on the tree shrew’s platelets. In vitro study showed that Vorapaxar has a maximum inhibitory rate with 40% on tree shrew’s platelets aggregated by bovine thrombin. In vivo results revealed that a dose of 5mg/kg can prolong the occlussion time for about 8 mins (a result with no significant difference in statistics). Our models need to be optimized, and the tree shrew thrombosis models call for further investigations. The endotoxin response between human and mice, the most commonly used laboratory animal, differs dramatically. In our endotoxin response model of tree shrew immune cells, the expression of inducible nitric oxide synthase is significantly different. The endotoxin response of the tree shrew’ immune cells was similar to the condition of human, indicating a possibly suitable model of the tree shrew in bacterial infections.
修改评论