The Effects Of Simvastatin Pretreatment On The Expression Of Bcl-2 And Bax Of Lung Microvascular Endothelial Cells By Neurogenic Pulmonary Edema Of Rats

Objectives:To investigate the effects of survival rate of simvastatin pretreatment on the neurogenic pulmonary edema rats and to explore its potential molecular mechanism.Methods:Totally 60 eight weeks old weight 250-300 g SD rats were divided into four groups, according to the method of random number table. They were control group,neurogenic pulmonary edema group,simvastatin 20mg/kg/d intervention group and simvastatin 40mg/kg/d intervention group.Control group and neurogenic pulmonary edema group gave normal diet, simvastatin 20 mg/kg/d intervention group and simvastatin 40 mg/kg/d intervention group gave respectively with different doses of simvastatin to fill the stomach, to feed four weeks later. The model of neurogenic pulmonary edema was induced by cerebellum medulla oblongata pool puncture injections.To Calculation on different time points the survival rate of the rats and to draw survival curve, to calculate the lung wet-to-dry weight of the rats, and to observe the pathological changes on the lung specimens, PT- PCR was used to detect the quantity of Bcl- 2 and Bax m RNA, Western blot was used to detect the quantity of Bcl- 2 and Bax protein.Results:1.Compared with control group, neurogenic pulmonary edema group, simvastatin 20 mg/kg/d intervention group and simvastatin 40 mg/kg/d group rats, survival rate were decreased(P < 0.05), compared with neurogenic pulmonary edema group, simvastatin 20 mg/kg/d intervention group and simvastatin 40 mg/kg/d group rats, survival rate were increased(P < 0.05), but simvastatin 20 mg/kg/d intervention group compared with 40 mg/kg/d group rats, survival rate was not statistically significant(P > 0.05). 2.Compared with control group, neurogenic pulmonary edema group, simvastatin 20 mg/kg/d intervention group and simvastatin 40 mg/kg/d group rats, lung wet-to-dry weight were increased(P < 0.05), compared with neurogenic pulmonary edema group, simvastatin 20 mg/kg/d intervention group and simvastatin 40 mg/kg/d group rats, lung wet-to-dry weight were decreased(P < 0.05), but simvastatin 20 mg/kg/d intervention group compared with 40 mg/kg/d group rats, lung wet-to-dry weight was not statistically significant(P > 0.05). 3.In control group alveolus structure is normal, not have any effusion.the rest of the group rats all have different degrees destruction of alveolar wall, alveolar volume increase, a lot of pink exudate could be seen in the pulmonary alveoli.Compared with neurogenic pulmonary edema group, simvastatin 20 mg/kg/d intervention group and simvastatin 40 mg/kg/d group,the alveolar exudate to a lesser degree.But simvastatin 20 mg/kg/d intervention group compared with 40 mg/kg/d group,the degree of alveolar exudatewas not obvious difference. 4.Compared with control group, neurogenic pulmonary edema group, simvastatin 20 mg/kg/d intervention group and simvastatin 40 mg/kg/d group,the m RNA of Bcl-2 and Bax expression levels were up-reulated(P < 0.05).Compared with neurogenic pulmonary edema group, simvastatin 20 mg/kg/d intervention group and simvastatin 40 mg/kg/d group,the m RNA of Bcl-2 expression level was up-reulated(P < 0.05),the m RNA of Bax expression level was down-reulated(P < 0.05).But simvastatin 20 mg/kg/d intervention group compared with 40 mg/kg/d group,the m RNA of Bcl-2 and Bax expression levels were not statistically significant(P > 0.05). 5.Compared with control group, neurogenic pulmonary edema group, simvastatin 20 mg/kg/d intervention group and simvastatin 40 mg/kg/d group,the protein of Bcl-2 and Bax expression levels were up-reulated(P < 0.05).Compared with neurogenic pulmonary edema group, simvastatin 20 mg/kg/d intervention group and simvastatin 40 mg/kg/d group,the protein of Bcl-2 expression level was up-reulated(P < 0.05),the protein of Bax expression level was down-reulated(P < 0.05).But simvastatin 20 mg/kg/d intervention group compared with 40 mg/kg/d group,the protein of Bcl-2 and Bax expression levels were not statistically significant(P > 0.05).Conclusions:Simvastatin pretreatment could improve the NPE rat survival rate, reduced the level of pulmonary edema,the underlying mechanism mighe be to up-regulation of Bcl-2 and down-regulation of Bax,reduced the number of apoptosis of pulmonary microvascular endothelial cells by the neurogenic pulmonary edema rats.