陕西医学杂志2025，Vol.54Issue(11)：1463-1469,7.DOI:10.3969/j.issn.1000-7377.2025.11.004
延胡索乙素通过调控Keap1/Nrf2通路缓解大鼠前列腺疼痛实验研究
Alleviation of prostate pain in rats by tetrahydropalmatine through the regulation of the Keap1/Nrf2 pathway
摘要
Abstract
Objective:To investigate the effects of tetrahydropalmatine(THP)on prostate pain in rats through the regulation of the Kelch-like ECH-associated protein 1(Keap1)/nuclear factor E2-related factor 2(Nrf2)path-way.Methods:Forty rats were divided into a sham operation group,a model group,and low-and high-dose THP groups,with 10 rats in each group.Except for the sham operation group,the other groups were used to establish an experimental autoimmune prostatitis(EAP)rat model.After modeling,the low-dose THP group was given 64 mg/kg THP by gavage,and the high-dose group was given 128 mg/kg THP by gavage.The other groups were given an equal volume of 0.9％sodium chloride solution by gavage once daily for 14 days.The pelvic pain response of the rats was assessed,and the prostate index was measured.Biochemical methods were used to detect the levels of serum ma-londialdehyde(MDA),superoxide dismutase(SOD)and total antioxidant capacity(T-AOC).HE staining was used to observe pathological changes in prostate tissue.The ELISA was used to detect the levels of cyclooxygenase-2(COX-2),prostaglandin E2(PGE2)and β-endorphin(β-EP)in prostate tissue.Fluorescence staining was used to de-tect the levels of reactive oxygen species(ROS)and mitochondrial membrane potential in prostate tissue.Immuno-histochemical staining was used to detect the positive rate of Keap1 and Nrf2 proteins in prostate tissue.Western blot was used to detect the expression of Keap1,Nrf2,heme oxygenase-1(HO-1)and NAD(P)H quinone dehydrogenase 1(NQO1)proteins in prostate tissue.Results:Compared with the sham operation group,the pain response rate and prostate index of the model group rats increased(all P＜0.05);the serum MDA level increased,and the SOD and T-AOC levels decreased(all P＜0.05).The interstitial tissue of the prostate showed a large number of inflammatory vacu-oles and disordered acinar structure,with obvious edema in the interstitial area.The levels of COX-2 and PGE2 in prostate tissue,the positive rate of Keap1 protein,and the expression level of Keap1 protein increased,while the con-tent of β-EP,the positive rate of Nrf2 protein,and the expression levels of Nrf2,HO-1 and NQO1 proteins decreased(all P＜0.05).The fluorescence intensity of ROS in prostate cells increased,and the mitochondrial membrane poten-tial decreased(all P＜0.05).Compared with the model group,the pain response rate and prostate index of rats in the low-and high-dose THP groups decreased(all P＜0.05);the serum MDA level decreased,and the SOD and T-AOC levels increased(all P＜0.05).Lymphocytic infiltration in prostatic tissue and the number of inflammatory vacuoles were significantly reduced.The levels of COX-2 and PGE2 in prostate tissue,the positive rate of Keap1 protein,and the expression level of Keap1 protein decreased,while the content of β-EP,the positive rate of Nrf2 protein,and the expression levels of Nrf2,HO-1 and NQO1 proteins increased(all P＜0.05).The fluorescence intensity of ROS in prostate cells decreased,and the mitochondrial membrane potential increased(all P＜0.05).The above indicators in the high-dose THP group were better than those in the low-dose THP group(all P＜0.05).Conclusion:THP can al-leviate prostate pain in rats.Its mechanism of action may be related to the regulation of the Keap1/Nrf2 pathway,in-hibition of oxidative stress in prostate tissue,improvement of mitochondrial dysfunction,reduction of inflammatory response and regulation of pain mediator levels.关键词
前列腺疼痛/延胡索乙素/氧化应激/线粒体功能/Kelch样ECH相关蛋白1/核因子E2相关因子2通路/大鼠Key words
Prostate pain/Tetrahydropalmatine/Oxidative stress/Mitochondrial function/Keap1/Nrf2 path-way/Rats引用本文复制引用
蔡丹,袁轶峰,孙雪琴,陈晓艳,刘欣,聂婷,杨丹妮..延胡索乙素通过调控Keap1/Nrf2通路缓解大鼠前列腺疼痛实验研究[J].陕西医学杂志,2025,54(11):1463-1469,7.基金项目
湖南省中医药科研计划项目(E2022009) （E2022009）
