Study on Mechanism of Platelet Aggregation Inhibitory Effects and Lung Tissue Protective Effects of Baicalein in Model Rats with Acute Pulmonary Embolism Based on Notch Signaling Pathway / 中国药房

ABSTRACT

OBJECTIVE：To explore the mec hanism of baicalein plat elet aggregation inhibitiory effect and lung tissue protective effect of baicalein in model rats with acute pulmonary embolism. METHODS ：Totally 36 rats were randomly divided into normal control group （n＝6）and modeling group （n＝30）. The acute pulmonary embolism model was established by autologous thrombus replication in modeling group ，and the sham operation of rats in normal control group was carried out. After modeling ， 30 model rats were randomly divided into model control group ，positive drug group （low molecular weight heparin calcium 0.01 mL/kg，subcutaneous injection ），baicalein low-dose ，middle-dose and high-dose groups （25，50，100 mg/kg，intraperitoneal injection），with 6 rats in each group. Normal control group and model control group were intraperitoneally injected constant volume of normal saline ；administration groups were given relevant medicine ，once a day ，for consecutive 7 d. After medication ， platelet aggregation rates of rats after activated with adenosine diphosphate （ADP） and arachidonic acid （AA） and platelet activation index （RPI）were detected ；lung histopathology was observed by HE staining ；serum platelet activation markers granule membrane（CD62P）and lysosomal membrane glycoprotein （CD63），growth differentiation factor- 15（GDF-15）and N-terminal B-type natriuretic peptide （NT-proBNP）were measured by ELISA. The mRNA expression levels of Notch 2，Notch3 and Notch signaling ligand PLL 1，JAG2 were detected by RT-PCR method. The protein expression levels of Notch 2，Notch3，DLL1 and JAG2 in lung tissue were detected by immunohistochemistry and Western blotting assay. RESULTS ：Compared with normal control group，plasma ADP-activated platelet aggregation rate ，AA-activated platelet aggregation rate ，RPI，serum levels of CD 62P， CD63，GDF-15 and NT-proBNP were increased significantly （P＜0.05）. The lung tissue of rats was in a state of severe inflammatory infiltration. mRNA and protein expression levels of Notch 2，Notch3，DLL1 and JAG 2 in lung tissue decreased significantly（P＜0.05）. Compared with model control group ，changes of above indexes of rats were improved significantly in baicalein groups （P＜0.05）. CONCLUSIONS ：Baicalein can reduce platelet aggregation and improve the pathological state of lung tissue in rats with acute pulmonary embolism. Its mechanism 0270） may be related to activating Notch signal pathway.