Protective effect of Fisetin on acute prostate injury in rats and underlying mechanism
Objective To investigate the protective effect and mechanism of prophylactic use of Fisetin on acute prostate injury in rats.Methods A rat model of acute prostate injury was established by injecting 2 needles of 3％sterile carrageenan saline solution into the left and right ventral lobes of the pros-tate of adult male Wistar rats(purchased from Wuhan Wanqian Jiaxing Biological Technology Co.,Ltd.),each needle of 50 μl,a total of 200 μl.The rats were randomly divided into 6 groups(6 cases each):sham operation group,model group,Fisetin low dose group(25 mg/kg),Fisetin middle dose group(50 mg/kg),Fisetin high dose group(100 mg/kg),positive drug group(1.08 g/kg).Fisetin treatment group and positive drug group were treated with intragastric administration once a day for 3 days before modeling,once a day on the day of modeling and 3 days after modeling(7 times in total).The sham opera-tion group and the model group were given the same dose of normal saline.The rats were sacrificed 3 days after injection of carrageenan.The prostate tissue was collected and the pathological changes of prostate tis-sue in each group were analyzed by hematoxylin-eosin(HE)staining.The expression of inflammatory fac-tors was analyzed by enzyme-linked immunosorbent assay(ELISA),real-time fluorescence quantitative PCR(RT-qPCR)and immunohistochemistry.The protein expression levels of inflammatory factors,toll-like receptor 4(TLR4),nuclear factor kappa B(NF-κB)and phosphorylated nuclear factor kappa B(p-NF-KB)were detected by Western blotting.One-way analysis of variance was used for comparison be-tween multiple groups,and t test was used for comparison between two groups.Results In the prostate tissues of rats,IL-6,IL-1β and TNF-α protein expression levels were significantly higher in the model group than in the Sham group,the Fisetin high-dose group,and the positive drug group[IL-6:(245.10± 7.73)vs.(77.65±6.28),(191.10±10.20),(197.80±9.31)pg/ml,t=6.632,4.237,3.924,P＜0.05;0.90±0.05 vs.0.61±0.05,0.36±0.08,0.31±0.07,t=4.218,5.918,6.684,P＜0.05;IL-1 β:(55.59±4.06)vs.(19.32±2.68),(40.32±2.75),(40.22±2.06)pg/ml,t=3.453,3.126,3.385,P＜0.05;1.07±0.08 vs.0.66±0.02,0.46±0.05,0.37±0.06,t=5.253,6.951,7.018,P＜0.05;TNF-α:(188.40±14.36)vs.(45.52±7.54),(125.50±5.92),(118.60± 14.89)pg/ml,t=7.158,4.135,3.372,P＜0.05;0.84±0.06 vs.0.53±0.05,0.44±0.04,0.40±0.02,t=4.824,5.827,6.785,P＜0.05].In the model group,the levels of TLR-4 and NF-κB/p-NF-κB in the prostate tissues were significantly higher than those in the Sham group,the Fisetin high-dose group,and the positive drug group(TLR-4:0.87±0.04 vs.0.12±0.01,0.30±0.03,0.44± 0.04,t=7.453,11.236,7.953,P＜0.05;NF-κB/p-NF-κB:1.38±0.04 vs.1.01±0.04,0.50± 0.04,0.42±0.05,t=8.582,16.639,16.328,P＜0.05).Conclusion Fisetin may reduce the level of inflammation in rats with prostate injury by inhibiting TLR4/NF-κB signaling pathway,thereby impro-ving prostate lesions.
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