目的 研究四君子湯對乙醇誘導(dǎo)的小鼠急性胃腸黏膜損傷的保護作用。方法 將60只小鼠隨機分為6組：對照組、模型組、奧美拉唑（陽性藥，4 mg·kg^-1）組和四君子湯低、中、高劑量（4、6、8 g·kg^-1）組，每組10只，連續(xù)ig給藥14 d后，在造模前全部小鼠禁食禁水24 h，末次給藥1 h后，除對照組外，其余各組小鼠每只ig無水乙醇10 mL·kg^-1誘發(fā)急性胃腸黏膜損傷。造模1 h后，脫頸椎處死小鼠后開腹，取出胃及十二指腸，觀察胃黏膜的損傷情況并拍照，分析小鼠胃黏膜損傷分數(shù)、治療指數(shù)；HE染色觀察胃及十二指腸黏膜病理組織學(xué)變化；試劑盒法檢測血清丙二醛（MDA）、總超氧化物歧化酶（SOD）水平； Westernblotting法檢測胃腸組織白細胞介素-1β （IL-1β）、白細胞介素-10 （IL-10）和腫瘤壞死因子-α （TNF-α）蛋白表達水平。結(jié)果 胃黏膜損傷評價結(jié)果顯示，與對照組比較，模型組小鼠胃黏膜有明顯出血帶；與模型組比較，各用藥組小鼠胃黏膜損傷有不同程度的改善，損傷分數(shù)均顯著降低（P＜0.05、0.001） ，四君子湯高劑量組治療效果最好，治療指數(shù)達到72.54%，與陽性藥奧美拉唑治療效果相當。HE染色結(jié)果顯示，模型組小鼠胃及十二指腸腺體排列紊亂，黏膜上皮細胞大量壞死、脫落，四君子湯發(fā)揮明顯改善作用。與模型組比較，四君子湯中、高劑量組以及奧美拉唑組小鼠血清中MDA水平顯著下降（P＜0.001）、SOD活性顯著升高（P＜0.05、0.001），胃及十二指腸組織IL-1β、TNF-α蛋白表達顯著下降（P＜0.05、0.01、0.001），IL-10蛋白表達顯著增加（P＜0.01）。結(jié)論 四君子湯可能通過抑制炎癥和抗氧化應(yīng)激反應(yīng)對乙醇誘導(dǎo)的小鼠急性胃腸黏膜損傷發(fā)揮保護作用。

Objective To study the protective effect of Sijunzi Decoction on acute gastrointestinal mucosal injury induced by ethanol in mice. Methods Sixty Kunming mice were randomly divided into control group, model group, omeprazole (positive drug, 4 mg·kg^-1) group, Sijunzi Decoction low, medium, high dose group (4, 6, and 8 g·kg^-1), with 10 mice in each group. After 14 days of continuous ig administration, all mice were fasting and water abstention for 24 h before modeling. After 1 h of last administration, except the control group, other mice in each group were given anhydrous ethanol of 10 mL·kg^-1 ig to induce acute gastrointestinal mucosal injury. One hour after the model was made, the mice were killed by cervical spondylosis, and then the stomach and duodenum were taken out. The injury of gastric mucosa was observed and photographed, and the injury score and treatment index of gastric mucosa were analyzed. HE staining was used to observe the histopathological changes of gastric and duodenal mucosa. The serum levels of malondialdehyde (MDA) and total superoxide dismutase (SOD) were detected by the kit method. Detection of interleukin-1β (IL-1β), Interleukin-10 (IL-10) and tumor necrosis factor- α (TNF-α) protein expression level in gastrointestinal tissue by Western blotting. Results The evaluation results of gastric mucosal injury showed that, compared with control group, the mice in the model group had obvious bleeding bands in the gastric mucosa. Compared with the model group, the gastric mucosal injury of mice in each drug group was improved to different degrees, and the injury score was significantly reduced (P< 0.05, 0.001), and the high dose group had the best treatment effect with a treatment index of 72.54%, which was comparable to the treatment effect of the positive drug omeprazole. HE staining results show that, the arrangement of gastric and duodenal glands in the model group of mice was disordered, and the mucosal epithelial cells were necrotic and detached in large numbers. Sijunzi Decoction could improve the anhydrous ethanol-induced gastrointestinal mucosal injury in mice. Compared with model group, the level of MDA in serum of mice in the middle and high dose groups of Sijunzi Decoction and omeprazole groups decreased significantly (P< 0.001), the activity of SOD increased significantly (P< 0.05、0.001), and the protein expression level of IL-1β and TNF-α in gastric and duodenal tissues decreased significantly (P< 0.05、0.01、0.001), and the expression of IL-10 protein increased significantly (P< 0.01). Conclusion Sijunzi Decoction has protective effect on ethanol-induced acute gastrointestinal mucosal injury in mice by inhibiting inflammatory response and anti-oxidative stress response.

R285.5

安徽省高校自然科學(xué)研究項目（KJ2019A0226）；2020年安徽省大學(xué)生創(chuàng)新創(chuàng)業(yè)訓(xùn)練計劃項目（S202010366003）