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Objective To explore the improvements of high-fat intake on lung injury induced by Paragonimus proliferus infection in rats, and to preliminarily explore the mechanisms underlying the role of cytochrome P450 4A1 (CYP 4A1) in the improve ments. Methods SD rats were randomly assigned into three groups, including the normal control group (n = 10), the infection and normal diet group (n = 12) and the infection and high-fat diet group (n = 12). Rats in the normal control group were fed with normal diet and without any other treatments, and animals in the infection and normal diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with normal diet, while rats in the infection and high-fat diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with high-fat diet. All rats were sacrificed 28 weeks post-infection, and serum samples and lung specimens were collected. Following hematoxylin-eosin (HE) staining of rat lung specimens, the rat lung injury was observed under an optical microscope, and alveolitis was evaluated using semi-quantitative scoring. Serum interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the cytochrome P450 4A1 (CYP 4A1) expression was quantified in rat lung specimens at transcriptional and translational levels using quantitative real-time PCR (qPCR) and Western blotting assays. Results Alveolar wall thickening, edema and inflammatory cell infiltration were alleviated 28 weeks post-infection with P. proliferus in rats in the infection and high-fat diet group relative to the infection and normal diet group, and no alveolar consolidation was seen in the infection and high-fat diet group. The semi-quantitative score of alveolitis was significantly higher in the infection and normal diet group [(2.200 ± 0.289) points] than in the normal control group [(0.300 ± 0.083) points] and the infection and high-fat diet group [(1.300 ± 0.475) points] (both P values < 0.05), and higher serum IL-1β [(151.586 ± 20.492)] pg/mL and TNF-α levels [(180.207 ± 23.379) pg/mL] were detected in the infection and normal diet group than in the normal control group [IL-1β: (103.226 ± 3.366) pg/mL; TNF-α: (144.807 ± 1.348) pg/mL] and the infection and high-fat diet group [IL-1β: (110.131 ± 12.946) pg/mL; TNF-α: (131.764 ± 27.831) pg/mL] (all P values < 0.05). In addition, lower CYP 4A1 mRNA (3.00 ± 0.81) and protein expression (0.40 ± 0.02) was quantified in lung specimens in the infection and normal diet group than in the normal control group [(5.03 ± 2.05) and (0.84 ± 0.14)] and the infection and high-fat diet group [(11.19 ± 3.51) and (0.68 ± 0.18)] (all P values < 0.05). Conclusion High-fat intake may alleviate lung injuries caused by P. proliferus infection in rats through up-regulating CYP 4A1 expression in lung tissues at both translational and transcriptional levels.
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Objective To observe the changes of microRNA141 expression in photodamaged skin of mice irradiated with ultraviolet B (UVB).Methods Eighteen C57/BL6 mice were equally divided into six groups to receive single irradiation on the hair-removed back with UVB of 0,30,60,90,180 and 270 mJ/cm2 respectively.Skin specimens were obtained from the irradiated sites 24 hours after the irradiation and subjected to paraffin embedding followed by hematoxylin-eosin (HE) staining for the observation of histopathological changes.Real-time quantitative PCR was performed to determine the miRNA141 expression in skin specimens,immunohistochemical staining (IHC) to quantify the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) protein.The TargetScan database was employed for the prediction of miRNA141 targets,and Gostat analysis for functional clustering.Data were processed using SPSS version 13.0 software,and intergroup comparisons were done by analysis of variance.Results The relative expression level of miRNA141 in skin tissue was 2.1354 ± 0.4289,2.4333 ± 0.2517,2.9328 ± 0.3126,3.4125 ± 0.3606,4.5667 ± 0.4014 and 6.7428 ± 0.5158 in mice irradiated with UVB of 0,30,60,90,180 and 270 mJ/cm2 respectively.There was a positive correlation between the expression level of miRNA141 and radiation dose (r =0.992,P ＜ 0.01).Gostat analysis showed that the targets of miRNA141 were mainly related to transcription regulation and signaling transduction.Moreover,PTEN expression gradually decreased with the increase in radiation dose.Conclusions miRNA141 may be involved in UVB-induced photodamage and inflammatory response,and PTEN may play a regulatory role in this process.
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Objective To investigate the expression changes of microRNA 146a (miRNA146a) in UVBdamaged mouse skin. Methods C57/BL6 mice were divided into dose groups to be irradiated on the back with UVB of 30, 60, 90, 180, 270 mJ/cm2 respectively for 24 hours, and time groups irradiated with UVB of 180 mJ/cm2 for 1, 12, 24 and 48 hours respectively. The mice received no irradiation served as the control. Skin samples were subsequently obtained from the irradiated sites of mice and subjected to real-time fluorescent PCR for the detection of miRNA146a expression as well as immunohistochemical staining (IHC) for the detection of STAT3. Results The expression levels of miRNA146a were 0.01158 ± 0.00098, 0.01083 ± 0.00104,0.00872 ± 0.00031, 0.00851 ± 0.00033, 0.00810 ± 0.00057 and 0.00770 ± 0.00031 in the unirradiated control mice and mice irradiated with UVB of 30, 60, 90, 180, 270 mJ/cm2 for 24 hours, respectively, 0.00730 ±0.00036, 0.00805 ± 0.00035, 0.00810 ± 0.00057 and 0.00837 ± 0.00039 in mice irradiated with UVB of 180mJ/cm2 for 1, 12, 24 and 48 hours, respectively. IHC suggested an intensive expression of phosphorylated STAT3 in mice irradiated with a high dose UVB. Conclusions miRNA146a may play an essential role in the mechanism of UVB-induced photodamge, which is mainly correlated with the negative regulation of inflammatory reaction likely mediated by the JAK/STAT3 signal transduction pathway.