Mesenchymal stem cells joint simvastatin therapy improves oleic acid induced acute lung injury in rats

Acute lung injury (ALI) is still a complex problem that has no special method to deal with. Mesenchymal stem cells (MSCs) treatment is reported to be beneficial in ALI model. Though simvastatin has no significant effect in ALI model, it also has some mechanisms such as suppressing inflammation in theory. We hypothesized that the joint use of MSCs and Simvastatin has a better effect on ALI treatment. The rats were assigned to the following groups: Blank group as the vehicle; other animals received intravenous oleic acid (OA) treatment to induce ALI and were allocated to groups as follow: Control group, received intravenous PBS; Simvastatin group, received oral simvastatin treatment; MSCs group, received intravenous MSCs; Joint group received both simvastatin and MSCs treatment. All treatments were given at 4 h and 24 h after ALI was established. 48 h after the OA-ALI model was established, injury score of morphology of lung tissue, wet/dry ratio were calculated. Arterial blood pressure (PaO2), the level of IL-6, IL-10 and TNF-alpha in serum were assessed. In order to find the possible mechanism, an in vitro experiment was designed as follow: There are two groups involved, Simvastatin group (n= 12), 1x10(5) MSCs were cultured with 7.25 ng simvastatin in 500 mu l serum-free MSC condition medium (MSC-CM); Control group (n= 12), 1x105 MSCs were cultured in 500 mu l serum-free MSC-CM alone. 24 hours later, the level of Keratinocyte growth factor (KGF) in MSC-CM was examined. Rats in joint group decreased the level of IL-6 (P=0.02) and TNF-alpha (P=0.03) in serum and increased IL-10 (P= 0.02), and decreased the injury score (P=0.1) of lung tissue. The in vitro experiments showed that, co-culture with simvastatin, the level of KGF in Simvastatin group was significantly higher (P= 0.02) than that in control group. Joint use of MSCs and simvastatin can significantly improve OA-ALI, and simvastatin's ability to stimulate MSCs to secret more KGF may be the probable mechanism.