Abstract:Aim To explore the effect and potential mechanisms of simvastatin pretreatment on neurogenic pulmonary edema (NPE) in rats. Methods The SD rats were randomly divided into control group, NPE group, simvastatin 20 mg group and simvastatin 40 mg group. The rats in the simvastatin group were pretreated with simvastatin for 4 weeks according to 20 mg/(kg·d) and 40 mg/(kg·d) by intragastric administration, respectively. The NPE models of rats except the control group were induced by cerebellomedullary cistern puncture after pretreatment of 4 weeks. The 24 h survival rates of rats were evaluated by Kaplan-Meier method. At 6 h following operation, the severity of pulmonary edema, lung tissue pathological changes of rats were evaluated by Wet Dry proportion method and HE staining, respectively. The apoptosis rate, protein and mRNA expressions of Bcl-2 and Bax of primary cultured PMVEC were detected by flow cytometry, Western blot and RT-PCR, respectively. Results Compared with the control group, the Wet Dry proportion of lung increased significantly, and the pulmonary interstitial edema and alveolar edema of the rats were obvious by HE staining and the apoptosis rate of PMVEC increased significantly at 6 h following operation in the NPE group. The 24 h survival rates of rats in the NPE group decreased significantly. The protein and mRNA expressions of Bcl-2 of PMVEC were downregulated, but the protein and mRNA expressions of Bax were upregulated in the NEP group. While the severity of pulmonary edema and survival rates of the 20 mg/(kg·d) simvastatin pretreatment rats decreased significantly when compared with that of rats in the NPE group. And the apoptosis rate of PMVEC decreased in the 20 mg/(kg·d) simvastatin pretreatment rats. The protein and mRNA expressions of Bcl-2 in the PMVEC were upregulated but the protein and mRNA expressions of Bax were downregulated in the simvastatin pretreatment rats. When compared with the 20 mg/(kg·d) simvastatin pretreatment rats, these parameters changes more significantly in the 40 mg/(kg·d) simvastatin pretreatment rats. Conclusions The study shows that simvastatin pretreatment decreases the severity of NPE and improves survival rate of rats. One of the mechanisms may decrease the apoptosis rate of PMVEC through upregulating the expression of Bcl-2 and downregulating the expression of Bax. It is implied that simvastatin may play a role in the prevention and treatment of NPE, but it needs to be further confirmed by clinical researchs.