Mechanism of action of magnolol in the treatment of acute lung injury in a rat model of severe acute pancreatitis

Objective To investigate the therapeutic effect of magnolol on severe acute pancreatitis( SAP) with acute lung injury from the aspect of the functional block of intestinal lymphatic circulation by magnolol. Methods A total of 30 healthy male Sprague-Dawley rats were randomly divided into sham-operation group,SAP group,and magnolol treatment group,with 10 rats in each group. The rats in the sham-operation group were given laparotomy to flip the pancreas,followed by abdominal closure; the rats in the SAP group were given retrograde pancreaticobiliary injection of 3. 75% sodium taurocholate to establish a rat model of SAP; the rats in the magnolol treatment group were given injection of magnolol 0. 2 mg/kg via the penile vein at 15 minutes before modeling. The three groups were compared in terms of pathological changes of the lung and the intestine,pathological score,the levels of D-lactic acid( DLA),diamine oxidase( DAO),high-mobility group box 1( HMGB1),receptor for advanced glycation end products( RAGE),interleukin-1β( IL-1β),interleukin-8( IL-8),interleukin-10( IL-10),and tumor necrosis factor-α( TNFα) in serum,lymphatic fluid,and tissue homogenate of the lung and the intestine,and the level of Toll-like receptor 4( TLR4) in lymphatic fluid. An analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups. Results The SAP group had congestion,edema,inflammatory cell infiltration,and bleeding in the pulmonary interstitium,and the magnolol treatment group had mild bleeding and inflammatory cell infiltration in the pulmonary interstitium,with a significantly lower degree than the SAP group. Compared with the SAP group,the magnolol treatment group had significantly lower serum levels of DAO,DLA,IL-1β,IL-8,TNFα,HMGB1,and RAGE( all P < 0. 05) and significantly lower levels of DAO,DLA,IL-1β,IL-8,TNFα,HMGB1,and RAGE in the lymphatic fluid( all P < 0. 05). Compared with the SAP group,the sham-operation group had sig-nificantly lower serum levels of DAO,DLA,IL-1β,IL-8,TNFα,HMGB1,and RAGE( all P < 0. 05) and significantly lower levels of DAO,DLA,IL-1β,IL-8,TNFα,HMGB1,and RAGE in the lymphatic fluid( all P < 0. 05). Compared with the SAP group,the magnolol treatment group had significantly lower levels of IL-1β,IL-8,TNFα,HMGB1,and RAGE in lung tissue( all P < 0. 05) and intestinal tissue( all P < 0. 05). Compared with the SAP group,the sham-operation group had significantly lower levels of IL-1β,IL-8,TNFα,HMGB1,and RAGE in lung tissue( all P < 0. 05) and intestinal tissue( all P < 0. 05). Compared with the SAP group,the magnolol treatment group and sham-operation group had a significant reduction in the protein expression of TLR4 in the lymphatic fluid( all P < 0. 05). Conclusion Magnolol can improve intestinal barrier function and alleviate lung injury in SAP by blocking intestinal lymphatic circulation,reducing the levels of inflammatory factors,and inhibiting the HMGB1-TLR4/NF-κB signal transduction pathway.