Abstract
Purpose: To determining the expression and role of the Notch signaling pathway (NSP) in phosgene inhalation-induced lung injury in rats, and the therapeutic effect of bone marrow mesenchymal stem cell (MSC) on the lung lesions.Methods: Wistar rats (220 - 280 g) were randomly assigned to air inhalation group, phosgene inhalation group, and mesenchymal stem cell (MSC) intervention group. Each group had 8 rats. Directional flow phosgene inhalation device was used to produce phosgene inhalation-induced lung injury in the rats. Serum inflammatory cytokines (TNF-α, IL-8 and IL-6) were determined using ELISA assay kits. The expressions of proteins related to the NSP (Notch1, Notch2, Hes1, Hes5) were quantified using Western blot.Results: Phosgene inhalation brought about significant increase in TNF-α, IL-8 and IL-6 levels (p < 0.01), but MSC intervention significantly reduced the expressions of these inflammatory factors to varying degrees (p < 0.05), although their levels were still significantly high, relative to the air inhalation group. Results from western blot showed that the Notch1, Notch2, Hes1 and Hes5 were upregulated in the phosgene inhalation group, when relative to the air inhalation group (p < 0.01). Protein expressions in the MSC intervention group were lower than those in the non-intervention groups (p < 0.05).Conclusion: Phosgene inhalation activates Notch signaling pathway, while MSC intervention inhibits this signaling pathway. Thus, inhibition of NSP may be implicated in the protective effect of MSC therapy against phosgene-induced lung injury.Keywords: Phosgene, Lung injury, Notch signalling pathway, Mesenchymal stem cells
Highlights
Phosgene is widely used as an important chemical raw material [1,2,3,4]
This index was significantly lower in the mesenchymal stem cell (MSC) intervention group than in the phosgene inhalation group (p < 0.05)
This indicated that phosgene inhalation aggravated pulmonary edema and that MSC intervention alleviated the resultant inflammatory responses, exudation and pulmonary edema (Table 1)
Summary
Phosgene is widely used as an important chemical raw material [1,2,3,4]. The Shanghai Chemical Industry Park is one of China’s largest investments. To laboratory environment, they were assigned to three groups: air inhalation group, phosgene inhalation group and MSC intervention group (8 rats per group). Directional flow phosgene inhalation device (provided by the Bayer Health & Medical Care Research Center) was used to establish a rat model of phosgene inhalation-induced lung injury. Lung tissues were processed into conventional pathological sections and subjected to H & E staining, followed by microscopic examination. The damage to lung tissue structure in the MSC group was still more serious than that in the air inhalation group (Figure 1). Total proteins were extracted from lung tissues and quantified. The resultant protein bands were transferred to polyvinylidene membranes and blocked using 5 % defatted milk powder at room temperature. Thereafter, the corresponding secondary antibodies (1:2500 dilution) were added dropwise, followed by further incubation of the membrane at room temperature for 1 h.
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