目的 觀察大黃蟲丸對(duì)肝纖維化模型大鼠肝組織病理學(xué)及其細(xì)胞凋亡的影響，探討其抗肝纖維化的作用機(jī)制。方法 將30只SD大鼠隨機(jī)分為對(duì)照組、模型組和大黃蟲丸組，后兩組行CCl₄誘導(dǎo)肝纖維化造模，8周后大黃蟲丸組大鼠ig大黃蟲丸0.45 g/kg，另兩組給予等量生理鹽水，同時(shí)稱體質(zhì)量。連續(xù)ig 4周后，斷頭處死各組大鼠，摘取肝臟，觀察色澤、質(zhì)地并稱重，計(jì)算肝臟指數(shù)（LI）；采用HE染色、Masson染色法光鏡下觀察各組肝組織病理改變，采用纖維化半定量計(jì)分系統(tǒng)結(jié)合測(cè)量膠原纖維面積密度，評(píng)估肝纖維化程度；采用TUNEL法檢測(cè)肝臟細(xì)胞凋亡，計(jì)算凋亡指數(shù)（AI）。結(jié)果 大黃蟲丸組大鼠肝的色澤和質(zhì)地介于對(duì)照組和模型組之間。與模型組比較，大黃組蟲丸組大鼠的LI、炎癥活動(dòng)度半定量、纖維化半定量評(píng)分、膠原纖維面積密度和細(xì)胞凋亡指數(shù)（AI）明顯下降，兩組比較差異均具有統(tǒng)計(jì)學(xué)意義（P<0.01）。HE染色顯示大黃蟲丸組大鼠的肝小葉結(jié)構(gòu)破壞較輕，肝索排列紊亂、肝細(xì)胞變性得到改善，匯管區(qū)增生不明顯。Masson染色顯示大黃蟲丸組大鼠肝小葉結(jié)構(gòu)紊亂有所改善，匯管區(qū)膠原纖維沉積和小葉內(nèi)纖維間隔明顯減少。FITC熒光標(biāo)記染色顯示大黃蟲丸組肝小葉結(jié)構(gòu)較清晰，可見(jiàn)少量凋亡細(xì)胞。結(jié)論 大黃蟲丸可以降低大鼠的LI、炎癥活動(dòng)度半定量、纖維化半定量評(píng)分和膠原纖維面積密度，可能通過(guò)抑制肝細(xì)胞凋亡來(lái)改善大鼠肝纖維化程度。

Objective To observe the effect of Dahuang Zhechong Pills on hepatic histopathology and apoptosis in rats with experimental hepatic fibrosis for exploring the mechanism of Dahuang Zhechong Pill on anti-hepatic fibrosis. Methods Thirty SD rats were randomly divided into control group, model group, and Dahuang Zhechong Pill group. And the ones of latter two groups were used to establish the CCl₄-induced liver fibrosis model. After 8 weeks, the rats in Dahuang Zhechong Pills group were ig Dahuang Zhechong Pills 0.45 g/kg, while the ones of other two groups only given normal saline. After 4 weeks, the rats in each group were sacrificed by breaking head, their livers were taken out to observe the color and texture, and weighed for calculating the liver index (LI). HE and Masson staining were used to observe the pathological changes of liver tissues in each group under light microscope. A semi quantitative scoring system of fibrosis combined with the measurement of the area density of collagen fiber was used to evaluate the degree of hepatic fibrosis. TUNEL method was used to detect the apoptosis of liver cells by the apoptosis index (AI). Results The color and texture of the liver in Dahuang Zhechong Pills group were between those in the control and model groups. Compared with the model group, LI, inflammatory activities, the semi-quantitative scores of fibrosis, the area density values of collagen fiber, and AI of hepatic tissues of rats in Dahuang Zhechong Pill group were significantly decreased (P < 0.01). HE staining showed that the hepatic lobules of rats were less damaged, liver cords were disorganized, hepatocyte degeneration was improved, and the hyperplasia in the manifold area was not obvious in Dahuang Zhechong Pill group. Masson staining showed the structural disorder of hepatic lobule in rats was improved, and collagen deposition and interlobular interlobular septum were decreased obviously in Dahuang Zhechong Pill group. FITC fluorescent staining showed that the liver lobule structure of rhubarb pills group was clear, and a small number of apoptotic cells could be seen. Conclusion Dahuang Zhechong Pills can decrease LI, inflammatory activities, the semi-quantitative scores of fibrosis, and the area density values of collagen fiber, and maybe improve the liver fibrosis in rats by inhibiting the hepatocyte apoptosis.

R285.5

云南省自然科學(xué)基金高校聯(lián)合項(xiàng)目（2017FH001-076）；國(guó)家級(jí)大學(xué)生創(chuàng)新訓(xùn)練項(xiàng)目（201810679008、201810679009）