目的 研究藏藥二十五味鬼臼丸對(duì)苯酚膠漿致宮頸炎模型大鼠的治療作用及機(jī)制。方法 將雌性SD大鼠48只隨機(jī)分為對(duì)照組、模型組及二十五味鬼臼丸低、中、高劑量（0.2、0.4、0.8 g·^kg-1）組和抗宮炎片（0.47 g·^kg-1）組，每組8只。除對(duì)照組外，其余5組建立25%苯酚膠漿致宮頸炎大鼠模型，各藥物組分別以相應(yīng)藥物ig給藥，每日1次，連續(xù)給藥12 d后取材。觀察大鼠外陰炎癥程度評(píng)分、子宮指數(shù)、子宮解剖形態(tài)學(xué)改變；采用蘇木精-伊紅（HE）染色觀察大鼠子宮組織病理學(xué)改變；采用酶聯(lián)免疫吸附測(cè)定（ELISA）法檢測(cè)子宮組織中超氧化物歧化酶（SOD）、丙二醛（MDA）含量變化；采用實(shí)時(shí)熒光定量PCR（qRT-PCR）法和蛋白免疫印跡（Western blotting）法檢測(cè)子宮組織中核因子E2相關(guān)因子（Nrf2）、血紅素氧合酶-1（HO-1）、NADPH氧化酶4（Nox4）的mRNA和蛋白表達(dá)情況。結(jié)果 與對(duì)照組比較，模型組大鼠外陰炎癥評(píng)分、子宮指數(shù)、子宮組織中MDA水平、Nox4的mRNA和蛋白表達(dá)均顯著升高（P＜0.01），體質(zhì)量、SOD活性、Nrf2、HO-1的mRNA和蛋白表達(dá)均顯著降低（P＜0.01），子宮組織出現(xiàn)不同程度的病理變化；與模型組比較，二十五味鬼臼丸能明顯降低外陰炎癥評(píng)分、子宮指數(shù)、子宮組織中MDA水平、Nox4的mRNA和蛋白表達(dá)（P＜0.05、0.01），升高體質(zhì)量及子宮組織中SOD活性和Nrf2、HO-1的mRNA和蛋白表達(dá)（P＜0.05、0.01），減輕子宮頸炎癥損傷程度。結(jié)論 二十五味鬼臼丸可能通過(guò)抑制Nox4的表達(dá)，激活Nrf2/HO-1通路，發(fā)揮抗氧化作用，減輕炎癥反應(yīng)，從而抑制宮頸炎發(fā)展。

Objective To study the therapeutic effects and mechanism of Tibetan medicine Ershiwuwei Guijiu pills (EGP) on cervicitis model rats induced by phenol mucilage. Methods Totally 48 female SD rats were randomly divided into control group, model group, EGP low, medium and high dose group (0.2, 0.4, 0.8 g·kg^-1) and Kanggongyan Tablets group (0.47 g·kg^-1), with eight rats in each group. Except for control group, the rats in the other five groups were successfully established with 25% phenol mucilage cervicitis, and then the rats in each drug group were given the corresponding drugs by gavage once a day for 12 consecutive days. The vulvar inflammation degree score, uterine index, and uterine anatomical morphological changes were observed. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of the uterus in rats. The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in uterine tissues were detected by enzyme-linked immunosorbent (ELISA). The expression of mRNA and protein in uterine tissues by nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (HO-1), and NADPH oxidase 4 (Nox4) were detected by real-time fluorescent quantitative PCR (qRT-PCR) and Western blotting. Results Compared with control group, the vulvar inflammation score, uterine index, the content of MDA, the expression of Nox4 mRNA and protein in uterine tissue of the model group were significantly increased (P＜0.01), the activity of SOD and the expression of Nrf2, HO-1 mRNA and protein were significantly decreased (P＜0.01), and different degrees of pathological changes were observed in uterine tissue; Compared with model group, each dose of EGP group could significantly decrease the vulva inflammation score, uterine index, the content of MDA, the expression of Nox4 mRNA and protein in uterine tissue (P＜0.05 and 0.01), and increase the activity of SOD and the expression of Nrf2, HO-1 mRNA and protein in uterine tissue (P＜0.05 and 0.01). Conclusion EGP may inhibit the development of cervicitis by inhibiting the expression of Nox4, activating the Nrf2/HO-1 pathway, exerting antioxidant effects, and reducing the inflammatory response, thereby inhibiting the development of cervicitis.

R285.5

國(guó)家自然科學(xué)基金資助項(xiàng)目（81470247）