Objective To explore the effect of drug-regulation on peroxisome proliferator-activated receptor-γ/retinoid X receptor-α (PPAR-γ/RXR-α) signalling pathway to improve lung injury caused by Paragonimus proliferus infection in rats. Methods The P. proliferus were isolated from crabs collected in Yunnan Province, and SD rats were infected with 8 metacercariae per rat via subcutaneous injection at abdominal wall. The infected rats were divided into the high-fat-diet group, rosiglitazone group and bexarotene group, with 10 rats in each group, and were given with high-fat-feeding (high-fat diet), rosiglitazone [3 mg/(kg·d)], bexarotene [10 mg/(kg·d)] by gavage for 7 days. The infected and healthy rats were used as the infection control group and healthy control group. On 28 d post-mediated, the rats were sacrificed to collect lung tissue and heart apical blood. The lung tissue sections were prepared and stained with hematoxylin-eosin to assess the tissue damage and score the alveolitis semi-quantitatively. Serum interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) levels were detected by ELISA. The lung tissue total protein was extracted for examining relative expression levels of PPAR-γ/RXR-α signalling pathway-related key target proteins indluding PPAR-γ, RXR-α, fatty acid transporter 3 (FATP3), apolipoprotein A1 (ApoA1), nuclear factor kappa-B (NF-κB) signalling pathway proteins [p65, activator protein (AP1）], janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway proteins （JAK2, STAT3） by Western blotting. The inter-group data were compared using single-factor ANOVA analysis. Results All rats were successfully infected except 2 rats in the bexarotin group. Parasitic cysts were found in the lungs or the chest cavity. HE staining showed that in the infection control group, a large number of inflammatory cells infiltrated the alveolar septum, the alveolar wall thickened, and the alveolar cavity collapsed or closed. In the high-fat diet group, obvious inflammation injury was shown. Compared with the infection control group, the alveolar cavity inflation was slightly improved. The inflammatory cells of alveolar septum in the rosiglitazone group and bexarotene group were significantly reduced. Compared to the infection control group, the degree of alveolar wall thickening was significantly reduced, and the alveolar cavity inflation was significantly improved. The semi-quantitative alveolitis scores were 0.300 ± 0.053, 2.200 ± 0.189, 1.900 ± 0.320, 1.300 ± 0.301 and 1.500 ± 0.112 (F = 12.033, P < 0.05) in the healthy control group, the infection control group, the high-fat diet group, the rosiglitazone group and the bexarotene group, respectively. ELISA tests show that serum IL-1β levels in the healthy control group, infected control group, high-fat diet group, rosiglitazone group and bexarotene group were (103.23 ± 3.37), (111.59 ± 20.49), (110.13 ± 12.95), (89.91 ± 14.84) and (96.34 ± 19.03) pg/ml, respectively. TNF-α levels were (144.81 ± 1.35), (180.21 ± 23.38), (171.76 ± 27.83), (155.37 ± 13.67) and (143.24 ± 23.66) pg/ml, respectively. There was a significant difference among the five groups (F = 17.236, 13.558; P < 0.05). Western blotting showed that in the lung tissue of rats in the healthy control group, the infection control group, high-fatdiet group, rosiglitazone group, and bexarotene group, PPAR-γ relative expression level were 0.51 ± 0.09, 0.67 ± 0.06, 0.75 ± 0.08, 0.34 ± 0.02 and 0.56 ± 0.04, respectively; RXR-α were 0.89 ± 0.05, 0.15 ± 0.03, 0.81 ± 0.09, 0.22 ± 0.02 and 0.61 ± 0.10, respectively; FATP3 were 0.59 ± 0.06, 0.64 ± 0.06, 0.68 ± 0.09, 0.59 ± 0.09 and 0.55 ± 0.03, respectively; ApoA1 were 0.58 ± 0.04, 0.83 ± 0.11, 0.92 ± 0.19, 0.71 ± 0.04 and 0.63 ± 0.08, respectively, and the differences among the five groups were statistically significant (F = 25.70, 67.12, 8.94, 11.58; All P < 0.05). P65 the relative expression level were 0.25 ± 0.19, 1.01 ± 0.21, 0.27 ± 0.15, 0.32 ± 0.01 and 0.22 ± 0.11, respectively; AP1 were 0.11 ±0.09, 1.12 ± 0.36, 0.08 ± 0.02, 0.03 ± 0.01 and 0.02 ± 0.01, respectively; JAK2 were 0.76 ± 0.18, 1.11 ± 0.24, 0.34 ± 0.06, 0.42 ± 0.01 and 0.35 ± 0.04, respectively; STAT3 were 0.80 ± 0.33, 1.11 ± 0.27, 0.68 ± 0.22, 0.77 ± 0.06 and 0.68 ± 0.19, respectively, the difference between the 5 groups were statistically significant (F = 43.77, 85.19, 37.22, 17.63; All P < 0.05). Among them, the relative expression levels of PPAR-γ, FATP3, ApoA1, p65, AP1, JAK2 and STAT3 in the infection control group were higher than those in the healthy control group, while those in rosiglitazone group and bexarotene group were lower than those in the infection control group (all P < 0.05). Conclusion A lung injury model of rat infected with P. proliferus was established. The rat model demonstrated that PPAR-γ/RXR-α signalling pathway plays an important role in the mechanism of lung injury caused by P. proliferus infection, and regulation of this signalling pathway by drugs may exert anti-inflammatory effects by inhibiting the NF-κB and JAK/STAT signalling pathways, thereby, reducing the extent of lung injury severity.
