目的 探討消痔丸對(duì)醋酸誘導(dǎo)大鼠肛門(mén)潰瘍模型的藥效作用及其可能的作用機(jī)制。方法 以醋酸誘導(dǎo)大鼠肛門(mén)潰瘍模型，將造模成功大鼠分為模型組、消痔丸（0.81、1.62、3.24 g/kg）組、柑橘黃酮片（0.27 g/kg）組和痔炎消片（0.86 g/kg）組，另設(shè)置對(duì)照組，每組10只。對(duì)照組與模型組ig給予同等體積的0.1% CMC-Na溶液。各組連續(xù)ig給藥10 d，1次/d。觀察各組大鼠表觀指標(biāo)，并采用Image J軟件計(jì)算潰瘍面積；蘇木素–伊紅染色法觀察肛門(mén)直腸組織病理學(xué)，并進(jìn)行分級(jí)評(píng)分；酶聯(lián)免疫吸附法（ELISA）檢測(cè)大鼠肛門(mén)組織中基質(zhì)金屬蛋白酶-9（MMP-9）、腫瘤壞死因子-α（TNF-α）、白細(xì)胞介素-6（IL-6）含量；免疫組化法檢測(cè)肛門(mén)組織中誘導(dǎo)型一氧化氮合成酶（iNOS）、轉(zhuǎn)化生長(zhǎng)因子β1（TGFβ1）、血管內(nèi)皮生長(zhǎng)因子A（VEGFA）蛋白表達(dá)。結(jié)果 與模型組相比，消痔丸組可顯著改善醋酸所致大鼠肛周潰瘍、腫脹、黏液分泌等情況，加快大鼠肛周黏膜上皮修復(fù)，潰瘍面積縮小，減少間質(zhì)或黏膜下水腫及炎性細(xì)胞浸潤(rùn)和炎性滲出物；消痔丸組可抑制肛周組織中MMP-9、IL-6、TNF-α分泌和iNOS、VEGFA蛋白表達(dá)，增加TGF-β1表達(dá)（P＜0.05、0.001）。結(jié)論 消痔丸對(duì)醋酸誘導(dǎo)的肛門(mén)潰瘍模型治療作用顯著，主要通過(guò)抑制IL-6、TNF-α、MMP-9相關(guān)細(xì)胞因子分泌和iNOS、VEGFA蛋白表達(dá)，升高TGF-β1表達(dá)，從抗炎消腫、抑制基質(zhì)降解、促進(jìn)組織生長(zhǎng)因子表達(dá)等途徑，起到消腫生肌作用。

Objective To explore the pharmacodynamic effect and possible mechanism of Xiaozhi Pills on acetic acid induced anal ulceration rat model. Methods Rats with acetic acid-induced anal ulcer model were divided into model group, Xiaozhi Pills (0.81, 1.62, 3.24 g/kg) group, Citrus Bioflavonoids Tablets 0.27 g/kg group and Zhiyanxiao Tablets 0.86 g/kg group, and control group with 10 rats in each group. Control group and model group were given the same volume of 0.1% CMC-Na solution by gavage. Each group was given ig for 10 days, once daily. The apparent indexes of rats in each group were observed, and the ulcer area was calculated by Image J software. The histopathology of anus and rectum was observed by hematoxylin-eosin staining and graded. The contents of matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in rat anal tissue were detected by enzyme-linked immunosorbent assay (ELISA). The expression of inducible nitric oxide synthase (iNOS), transforming growth factor β1 (TGFβ1) and vascular endothelial growth factor A (VEGFA) protein in anal tissues was detected by immunohistochemistry. Results Compared with the model group, Xiaozhi Pills can significantly improve the perianal ulcer, swelling, and mucus secretion induced by acetic acid, accelerate the repair of perianal mucosal epithelium, and reduce interstitial or submucosal edema, inflammatory cell infiltration and inflammatory exudate. Xiaozhi Pills group could inhibit the secretion of MMP-9, IL-6, TNF-α and the protein expression of iNOS and VEGFA in perianal tissue, and increase the expression of TGF-β1 (P < 0.05, 0.001). Conclusion Xiaozhi Pills has a significant therapeutic effect on acetic acid induced anal ulcer model, mainly by inhibiting the secretion of IL-6, TNF-α, MMP-9 related cytokines and the expression of iNOS and VEGFA protein, increasing the expression of TGF-β1, and playing a role in reducing swelling and promoting muscle growth through anti-inflammation and detumification, inhibiting matrix degradation, and promoting the expression of tissue growth factor.

R285.5

國(guó)家自然科學(xué)基金重點(diǎn)資助項(xiàng)目(U21A20406);蘭州市人才創(chuàng)新創(chuàng)業(yè)項(xiàng)目(2022-RC-2)