机构地区:[1]中国中医科学院医学实验中心,北京100700 [2]陕西中医药大学第一临床医学院,陕西咸阳712046
出 处:《中国中医基础医学杂志》2024年第2期240-244,共5页JOURNAL OF BASIC CHINESE MEDICINE
基 金:中央级公益性科研院所基本科研业务费专项(JJPY-2022019)。
摘 要:目的基于核因子E2相关因子(nuclear factor erythroid2-related factor,Nrf)2信号通路探讨克癃胶囊改善前列腺增生的分子机制。方法取雄性SD大鼠60只随机分为正常组、模型组、假手术组、非那雄胺组和克癃高、中、低剂量组。采用睾丸切除术和皮下注射丙酸睾酮的方法建立良性前列腺增生(benign prostatic hyperplasia,BPH)大鼠模型,各药物治疗组大鼠在睾丸切除术后第8天,注射丙酸睾酮的同时以相应药物灌胃,持续给药28 d后处死。苏木素-伊红(hematoxylin-eosin,HE)染色观察前列腺组织病理学变化;ELISA检测各组大鼠血清中睾酮(testosterone,T),二氢睾酮(dihydrotestosterone,DHT),雌二醇(estradiol,E2)的含量;实时荧光定量PCR法检测各组大鼠前列腺组织中TNF-α、IL-1β、IL-6、Nrf2和NQO1的mRNA表达。结果与假手术组比较,BPH模型组大鼠前列腺组织中腺上皮呈立方状或高柱状,腺腔明显扩张,腺腔内分泌物明显增加;血清中T和DHT水平明显升高(P<0.05),E2水平明显降低(P<0.01);前列腺组织中TNF-α、IL-1β、IL-6 mRNA水平显著升高(P<0.01),Nrf2 mRNA和NQO1 mRNA的表达水平显著降低(P<0.01)。与模型组比较,克癃高剂量组大鼠高柱状腺上皮的数量明显减少,前列腺腺腔扩张也明显改善;克癃胶囊高、中剂量组大鼠血清E2表达水平明显升高(P<0.05),T和DHT表达水平显著降低(P<0.05),前列腺组织NQO1 mRNA水平显著升高(P<0.01);克癃高、中、低剂量组大鼠前列腺组织Nrf2 mRNA水平均显著升高(P<0.05),TNF-α、IL-1β、IL-6 mRNA水平均显著降低(P<0.05)。结论克癃胶囊可改善BPH大鼠前列腺组织的病理性增生,具体机制可能与其激活Nrf2信号通路、抑制炎症有关。Objective To investigate the molecular mechanism of improving prostatic hyperplasia based on nuclear factor erythroid2-related factor 2(Nrf2)signaling pathway.Methods Sixty male SD rats were randomly divided into blank control group,model group,sham group,finasteride group,and high,medium,and low dose groups of Kelong capsule.The Benign prostatic hyperplasia(BPH)models were established by orchiectomy and subcutaneous injection of testosterone cypionate.On the 8th day after orchiectomy,rats in each drug treatment group were injected with testosterone propionate and gavaged with corresponding drugs at the same time,and the HE staining was detected to observe the histopathological changes in the prostate.ELISA was used to measure the serum content of testosterone(T),dihydrotestosterone(DHT),and estradiol(E2)in each group,real-time qPCR method was used to detect the expression of TNF-α,IL-1βand IL-6,Nrf2,NQO1 mRNA in prostate tissue.Results Compared with the sham group,the glandular epithelium in prostate tissue of rats in BPH model group was cubic or highly columnar,the gland cavity was significantly dilated,the endosecretions in the gland cavity increased significantly.The expression of T and DHT in serum were significantly increased(P<0.05),the level of E2 was significantly reduced(P<0.01),the levels of TNF-α,IL-1βand IL-6 mRNA in rats prostate tissues were significantly increased(P<0.01),and the expression levels of Nrf2 mRNA and NQO1 mRNA were significantly decreased(P<0.01)in the rats of model group.Compared with the model group,the number of high columnar gland epithelium was significantly reduced,while the expansion of the prostate gland cavity was also significantly improved in the rats of high-dose group of Kelong capsule.The E2 expression levels in serum were significantly increased(P<0.05),while T and DHT levels were significantly reduced(P<0.05),and NQO1 mRNA expression was significantly increased(P<0.01)in the rats of high-dose and medium-dose groups of Kelong Capsule.In the high-dose and medium-dos
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