3.7 Compound 270 relieves the mice acute lung injury triggered
by intraperitoneal injection of LPS through eliminating lung
inflammation state
Despite oral administration with 270 does not affect the lung index of
mice injected LPS, but 270 reduced the plasma content of
pro-inflammation cytokines. Uncontrolled inflammation is an
indispensable mechanism of ALI, and TNF-α, IL-1β and IL‑6 are critical
mediators involved in the development of LPS-induced septic ALI
(Huang et al. , 2019). So we
assessed the effect of 270 on ALI. To detect the histological
variations, lung tissues underwent HE staining. There were no visible
histopathological lesions in the Veh group, and lung tissues from the
LPS group presented significant thickening of the alveolar septa, the
collapse of the alveolar and interstitial infiltration of inflammatory
cells, while 270 pretreatment effectively reduced these serious
pathological variations attributed to LPS (Figure 7A). The mRNA levels
of associated genes in lung determined by RT-PCR, and the expression of
TNF-α, IL-1β, MCP 1 and Nos2 in LPS-challenged mice lung tissues was
evidently enhanced, meanwhile the administration of 270 dose dependently
eliminated the increase of these pro-inflammation genes (Figure 7B).
Next, we tested the effect of 270 on the key proteins related to NF-κB
and JNK signaling pathways. Compared with the Veh group, the protein
levels of p-IKK, p-NF-κB in LPS group lung tissues were up-regulated,
and the protein level of IκB-α was down-regulated. Compared with the LPS
group, the expression of p-IKK, p-NF-κB and p-JNK protein was reduced by
270, and the level of IκB-α protein was elevated after treatment with
270 (Figure 7C,D). Our observations implied that 270 can protect mice
against LPS-induced septic ALI.