Effects of rapamycin and OSI-027 on α-SMA in lung tissue of SD rat pups with hyperoxic lung injury

Objective: To investigate the effect and significance of mammalian target of rapamycin (mTOR) inhibitors on the expression of α-SMA in lung injury induced by high volume fraction of inspired oxygen (hyperoxygen) in SD rat pups.

Methods: Seventy-two Sprague-Dawley rat pups (age: 3 weeks) were randomly divided into air + saline, hyperoxia + saline, hyperoxia + OSI-027, and hyperoxia + rapamycin groups. Animal models were constructed (n = 18). Hyperoxia was induced by continuous administration of 90% oxygen. Normal saline, OSI-027, and rapamycin are administered by intraperitoneal injection on 1d, 3d, 6d, 8d, 10d, 13d of the observation period, respectively. Following assessments were made on the 3rd, 7th, and 14th day of modeling: pathological changes in lung tissues, lung injury score, Western Blot to assess the distribution and expressions of mTOR, pS6K1, and α-SMA protein in lung tissues.

Results: In terms of time factors, the protein expressions of mTOR, pS6K1, and α-SMA increased with time. Except for the air group, the lung injury scores of the other groups increased with time, In terms of grouping factors, lung injury score in the air group was significantly lower than that in the other groups. In the hyperoxia group, the protein expressions of mTOR, PS6K1, and α-SMA were significantly higher than those in the other groups. The lung injury score in the hyperoxia group was significantly higher than that in the other groups. The lung injury score in the hyperoxia OSI group was significantly lower than that in the hyperoxia rapamycin group.

Conclusion: In hyperoxia lung injury, inhibiting the activation of mTOR signaling pathway can effectively reduce the expression of α-SMA; however, only mTORC1/2 dual inhibitor OSI-027 exhibited an anti-proliferative effect, and alleviated hyperoxia-induced lung injury and fibrosis in SD rat pups.