Effects of pirfenidone on chronic nonbacterial prostatitis in rats
Objective To investigate the effects of pirfenidone(PFD)on inflammatory response and apoptosis in chronic nonbacterial prostatitis(CNP)and its mechanism.Methods Wistar rats were randomly divided into sham group(injected with the same amount of normal saline),model group(injected with carrageenan),positive group(35 mg·kg-1 celecxib),compound C group(150 mg·kg-1 pirfenidone+0.2 mg·kg-1 compound C),experimental-L group(50 mg·kg-1 PFD),experimental-H group(150 mg·kg-1 PFD),10 mice per group.Mechanical pain threshold was determined by Von Frey fibrograph;tissue related protein expression was detected by Western blot assay;inflammatory factor expression was detected by enzyme-linked immunosorbent assay(ELISA);apoptosis was detected by TdT mediated dUDP nick end labeling(Tunel)assay.Raw264.7 was randomly divided into control group(normal culture),lipopolysaccharide(LPS)group(1 µg·mL-1 LPS),PFD group(1 μg·mL-1 LPS+4 mmol·L-1 PFD)and combined group(1 μg·mL-1 LPS+4 mmol·L-1 PFD+10 μmol·L-1compound C).The expression of inflammatory factors was detected by ELISA.Results The pain thresholds of sham operation group,model group,positive group,experimental-H group and compound C group were(45.33±5.09),(23.13±3.20),(35.27±4.65),(33.96±2.65)and(30.30±4.77)g,respectively;phosphorylated adenylate activated protein kinase(p-AMPK)protein expression levels were 0.84±0.11,0.33±0.07,0.31±0.05,0.65±0.09 and 0.20±0.04,respectively;the contents of interleukin-6(IL-6)were(80.10±3.33),(237.82±15.68),(91.30±5.57),(139.79±16.93)and(207.92±13.22)pg·mL-1,respectively;Tunel apoptosis rates were(3.57±0.18)%,(26.29±1.84)%,(12.16±0.76)%,(11.78±1.45)%and(15.76±1.05)%,respectively.The above indexes in the model group were compared with those in the sham group,the experimental-H group was compared with those in the model group,and the above indexes in the compound C group were compared with those in the experimental-H group,and the differences were significant(all P<0.05).IL-6 content in control group,LPS group,PFD group and combined group were(72.06±4.03),(328.03±27.80),(169.84±19.38)and(204.53±18.39)pg·mL-1,respectively.The above indexes were significantly different in LPS group compared with control group,PFD group compared with LPS group,and combined group compared with PFD group(all P<0.05).Conclusion Pirfenidone can reduce inflammation and apoptosis by inhibiting the polarization of macrophages towards M1 type,improvemen t of CNP pelvic pain.
pirfenidonechronic nonbacterial prostatitisinflammatory cytokinesapoptosismacrophage polarizationadenosine monophosphate activated protein kinase/nuclear factor kappa B signaling pathway