[Interventional effect of metformin on pulmonary inflammation and pulmonary fibrosis in silicotic rats].

Objective: To investigate the interventional effect of metformin on pulmonary inflammation and pulmonary fibrosis in silicotic rats. Methods: In April 2019, 48 Wistar male rats of SPF grade were randomly divided into negative control group, metformin control group, silicon dioxide (SiO2) model group, low, medium and high dose metformin intervention group according to the random number table method, 8 rats in each group. The SiO2 model group and the low, medium and high dose metformin intervention groups were given 1 ml 50 mg/ml of SiO2 by intratracheal instillation, the negative control group and the metformin control group were given 1 ml normal saline by intratracheal instillation. 24 hours later, the low, medium and high dose metformin intervention groups and the metformin control group were treated with 100, 200, 400 and 400 mg/kg metformin daily, the control and SiO2 model groups received normal saline daily. Then the rats were sacrificed at the 28th day after SiO2 exposure. The changes of rat body weight and pathological examination of rat lung tissue were observed, and the lung organ coefficient, the content of hydroxyproline (HYP) , the expression levels of inflammatory factors transforming growth factor beta1 (TGF-ß1) , tumor necrosis factor-alpha (TNF-α) , interleukin-1beta (IL-1ß) and the protein expression of E-cadherin (E-Cad) , Vimentin, α-SMA were detected. Results: Compared with the negative control group, SiO2 model group had a significant decrease in the body weight of rats (P<0.05) , lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-ß1, TNF-α, IL-1ß were all significantly increased (P<0.05) . Compared with the SiO2 model group, the weights of the rats in the medium and high dose intervention group of metformin increased significantly (P<0.05) . And after intervention with different doses of metformin, the lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-ß1, TNF-α and IL-1ß were significantly decreased (P<0.05) . Immunohistochemistry and Western blotting results showed that compared with the negative control group, the expression of E-Cad of the SiO2 model group was decreased, and the expression levels of Vimentin and α-SMA were significantly increased (P<0.05) . After metformin intervention, the expression of E-Cad was significantly increased, the expression levels of Vimentin and α-SMA were significantly decreased (P<0.05) . Conclusion: Metformin can reduce lung tissue inflammation and fibrosis in rats exposed to SiO2 dust, which may be related to reducing the expression of inflammatory factors in lung tissue and inhibiting the EMT process.

[Protective effect of recombinant adult serine protease inhibitor from Trichinella spiralis on sepsis-associated acute kidney injury in mice].

OBJECTIVE: To investigate the protective effect of recombinant adult serine protease inhibitor from Trichinella spiralis (TsadSPI) on sepsis-associated acute kidney injury in mice. METHODS: A total of 18 male BALB/c mice were randomly divided into the sham-operation group, the model group, and the TsadSPI treatment group, of 6 mice in each group. Sepsis-associated acute kidney injury was modeled in the model group and TsadSPI treatment group by cecal ligation puncture (CLP), while mice in the sham-operation group were only given exploratory laparotomy without ligation or perforation of the cecum. After 30 min of CLP, mice in the sham-operation group and the model group were intraperitoneally injected with PBS (100 µL), and mice in the TsadSPI treatment group were intraperitoneally injected with PBS (100 µL) containing TsadSPI (2 µg). At 12 h following modeling, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr) and urea nitrogen (BUN) were measured to assess the liver and kidney functions, and the changes of the mouse kidney structure were observed using HE staining. In addition, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-ß were measured using an enzyme-linked immunosorbent assay (ELISA), and the myeloid differentiation factor 88 (MyD88) and nuclear factor kappa-B (NF-κB) p65 expression was determined in kidney tissues using immunohistochemical staining. RESULTS: At 12 h following CLP, there were significant differences in the serum levels of ALT (F = 41.031, P < 0.001), AST (F = 54.757, P < 0.001), Cr (F = 24.142, P < 0.001) and BUN (F = 214.849, P < 0.001) among the three groups, and higher levels of ALT, AST, Cr and BUN were measured in model group than in the sham-operation group (P < 0.001), while lower ALT, AST, Cr and BUN levels were found in the TsadSPI treatment group than in the model group (P < 0.001). HE staining showed severe mouse kidney injuries following CLP, and TsadSPI treatment resulted in remarkable alleviation of the injury. ELISA measured significant differences in the TNF-α (F = 47.502, P < 0.001) and IL-6 levels (F = 222.061, P < 0.001) among the three groups, and showed a remarkable reduction in the TNF-α and IL-6 levels in the TsadSPI treatment group as compared to those in the model group (P < 0.001). In addition, there were significant differences in serum IL-10 (F = 16.227, P < 0.001) and TGF-ß levels (F = 52.092, P < 0.001) among the three groups, and higher IL-10 and TGF-ß levels were seen in the TsadSPI treatment group than in the model group (P < 0.001). Immunohistochemical staining showed greater MyD88 expression and a higher nuclear positive rate of NF-κB p65 in kidney tissues in the model group than in the TsadSPI treatment group. CONCLUSIONS: TsadSPI may reduce the MyD88 expression and nuclear positive rate of NF-κB p65 in mouse kidney tissues to up-regulate the expression of immunomodulatory factors and down-regulate the expression of pro-inflammatory cytokines, thereby protecting sepsis-associated acute kidney injury.