吡非尼酮对慢性非细菌性前列腺炎大鼠的作用  

Effects of pirfenidone on chronic nonbacterial prostatitis in rats

作　　者：杜宇峰 王颖新 陈煌辉 余慧 DU Yu-feng;WANG Ying-xin;CHEN Huang-hui;YU Hui(Department of Urology,Chenzhou First People's Hospital,Chenzhou 423000,Hunan Province,China;Department of Intensive Care Medicine,Chenzhou First People's Hospital,Chenzhou 423000,Hunan Province,China;Department of Reproductive Medicine,Chenzhou First People's Hospital,Chenzhou 423000,Hunan Province,China)

机构地区：[1]郴州市第一人民医院泌尿外科,湖南郴州423000 [2]郴州市第一人民医院重症医学科,湖南郴州423000 [3]郴州市第一人民医院生殖医学科,湖南郴州423000

出　　处：《中国临床药理学杂志》2024年第19期2858-2863,共6页The Chinese Journal of Clinical Pharmacology

摘　　要：目的探讨吡非尼酮(PFD)对慢性非细菌性前列腺炎(CNP)炎性反应和细胞凋亡的影响,及其作用机制。方法将Wistar大鼠随机分为假手术组(注射等量的0.9%NaCl)、模型组(注射1%角叉菜胶)、阳性组(35 mg·kg^(-1)塞来昔布)、compound C组(150 mg·kg^(-1)PFD+0.2 mg·kg^(-1)compound C)和低、高剂量组(50和150 mg·kg^(-1)PFD),每组10只。用Von Frey纤维丝测痛仪测定机械疼痛阈值,用蛋白质印迹法检测组织相关蛋白的表达水平,用酶联免疫吸附试验(ELISA)法检测炎性因子的表达水平,用原位末端转移酶标记法(Tunel)实验检测细胞的凋亡情况。将Raw264.7细胞随机分为对照组(正常培养)、脂多糖(LPS)组(1μg·mL^(-1)LPS)、PFD组(1μg·mL^(-1)LPS+4 mmoL·L^(-1)PFD)、联合组(1μg·mL^(-1)LPS+4 mmoL·L^(-1)PFD+10μmoL·L^(-1)compound C)。用ELISA法检测各组细胞炎性因子的表达水平。结果假手术组、模型组、阳性组、高剂量组、compound C组的疼痛阈值分别为(45.33±5.09)、(23.13±3.20)、(35.27±4.65)、(33.96±2.65)和(30.30±4.77)g,磷酸化-腺苷酸活化蛋白激酶蛋白相对表达水平分别为0.84±0.11、0.33±0.07、0.31±0.05、0.65±0.09和0.20±0.04,白细胞介素-6含量分别为(80.10±3.33)、(237.82±15.68)、(91.30±5.57)、(139.79±16.93)和(207.92±13.22)pg·mL^(-1),凋亡率分别为(3.57±0.18)%、(26.29±1.84)%、(12.16±0.76)%、(11.78±1.45)%和(15.76±1.05)%。模型组的上述指标与假手术组、高剂量组比较,compound C组的上述指标与高剂量组比较,在统计学上差异均有统计学意义(均P<0.05)。对照组、LPS组、PFD组和联合组的IL-6含量分别为(72.06±4.03)、(328.03±27.80)、(169.84±19.38)和(204.53±18.39)pg·mL^(-1),LPS组的上述指标与对照组、PFD组比较,联合组的上述指标与PFD组比较,在统计学上差异均有统计学意义(均P<0.05)。结论PFD通过抑制巨噬细胞向M1型极化,减轻炎症反应和凋亡,改善CNP盆腔疼痛。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(1μg·mL^(-1)LPS),PFD group(1μg·mL^(-1)LPS+4 mmol·L^(-1)PFD)and combined group(1μg·mL^(-1)LPS+4 mmol·L^(-1)PFD+10μmol·L^(-1)compound 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 contro

关 键 词：吡非尼酮 慢性非细菌性前列腺炎 炎性细胞因子 凋亡 巨噬细胞极化 腺苷酸活化蛋白激酶/核因子κB信号通路 

分 类 号：R974[医药卫生—药品]