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.