Curcumin upregulates mitofusin2 to alleviate acute lung injury in septic mice

Abstract

Objective To investigate the protective effect and mechanism of curcumin on acute lung injury in septic mice. Methods Totally 120 clean BALB/c male mice were randomly (random number) divided into 8 groups: sham group, sepsis group, curcumin control group, curcumin intervention group, negative virus-sepsis group, negative virus-curcumin intervention group, Mfn2 interference-sepsis group, and Mfn2 interference-curcumin intervention group, 15 rats in each group. Mice in the sepsis and the curcumin groups were given the cecal ligation and puncture (CLP) mice in the curcumin intervention and curcumin control groups were given curcumin 200 mg/(kg·d) for 1 week, and mice in the negative virus-sepsis group and negative virus-curcumin intervention groups were established by injection of a negative adeno-associated virus in the tail vein. The Mfn2 interference-sepsis and Mfn2 interference-curcumin intervention groups were established by injecting an adeno-associated virus carrying the Mfn2 interference sequence through the tail vein. Mice were sacrificed after 24 h in each group. The degree of lung injury was examined by lung wet-to-dry weight ratio and pathological examination. The inflammatory factors of alveolar lavage fluid including TNF-α and IL-6 were detected by ELISA, the activation of caspase-3, a key molecule for apoptosis, was detected by Western blot, and apoptosis was detected by TUNEL. The data were analyzed by SPSS 22.0 software, the count data was analyzed by χ2 test, and the comparison of measurement data between groups was analyzed by one-way ANOVA. Results Compared with the sham group, the wet-to-dry weight ratio of lung tissue in the sepsis group was significantly increased (71.11±3.78 vs 31.11±5.61, P=0.002), the histopathological score was significantly higher (P=0.006), the inflammatory factors TNF-α (P=0.001) and IL-6 (P=0.012) were dramatically increased, and the apoptosis of lung tissue and the expression of caspase-3 cleaved were also significantly increased (P=0.001). Compared with the sepsis group, the wet-to-dry weight ratio and the histopathological score of lung tissue in the curcumin-treated group was significantly lower (32.84±6.15 vs 71.11±3.78, P=0.004), and the inflammatory factors TNF-α(P=0.013) and IL-6 (P=0.003) were obviously decreased, and apoptosis and apoptosis-related protein caspase-3 cleaved expression were also dramatically decreased (P=0.012). After Mfn2 was down-regulated, Mfn2 interference-curcumin intervention group interfered with Mfn2. Compared with the sepsis group, the dry-to-wet weight ratio and the histopathological score of the lung tissue of the mice was not significantly decreased. Further studies found that after down-regulating Mfn2, compared with the Mfn2 interfere-sepsis group, Mfn2 interfere-curcumin intervention group had no such performance. The inflammatory factors TNF-α and IL-6 were not significantly decreased, and the apoptosis of lung tissue and the expression of apoptosis-related protein caspase-3 cleaved were not significantly reduced. Conclusion Curcumin may attenuate acute lung injury in sepsis by up-regulating the expression of Mfn2. Key words: Sepsis; Curcumin; Acute lung injury; Mitofusin2; Apoptosis