目的 研究知母皂苷元對(duì)脂多糖（LPS）誘導(dǎo)的小鼠急性肺損傷的保護(hù)作用。方法 將昆明小鼠隨機(jī)分為對(duì)照組、模型組、地塞米松（0.5 mg/kg）組、知母皂苷元（50、100、200 mg/kg）組。知母皂苷元50、100、200 mg/kg組小鼠ig相應(yīng)劑量知母皂苷元溶液，地塞米松組小鼠ip地塞米松磷酸鈉注射液，對(duì)照組和模型組小鼠ig等體積生理鹽水，1次/d，連續(xù)7 d。末次給藥1 h后，其余各組小鼠除對(duì)照組外均ip 10 mg/kg LPS溶液復(fù)制小鼠急性肺損傷模型。6 h后取各組小鼠左肺組織，計(jì)算肺濕/干質(zhì)量比（W/D）；采用蘇木精-伊紅（HE）染色法觀察肺組織病理形態(tài)學(xué)變化；采用酶聯(lián)免疫吸附測(cè)定法（ELISA）檢測(cè)血清中腫瘤壞死因子-α（TNF-α）、白細(xì)胞介素-6（IL-6）水平；采用Western blotting法檢測(cè)肺組織中鳥苷酸-腺苷酸合成酶（cGAS）、干擾素基因刺激因子（STING）的蛋白表達(dá)。結(jié)果 與模型組相比，知母皂苷元組小鼠左肺W/D值、血清中IL-6和TNF-α水平、肺組織中cGAS和STING的蛋白表達(dá)均顯著降低（P<0.05），肺組織病理學(xué)損傷均有所改善。結(jié)論 知母皂苷元可能通過抑制cGAS-STING通路，減少炎癥因子TNF-α、IL-6的分泌，從而保護(hù)LPS誘導(dǎo)的急性肺損傷。

Objective To study the protective effect of sarsasapogenin on LPS-induced acute lung injury in mice. Methods KM mice were randomly divided into control group, model group, dexamethasone (0.5 mg/kg) group, and sarsasapogenin (50, 100, 200 mg/kg) group. Mice in the 50, 100, and 200 mg/kg group were ig administered with the corresponding dose of the sarsasapogenin solution, the mice in the dexamethasone group were ig administered with Dexamethasone Sodium Phosphate Injection, and the control group and model group were ig administered with equal volume of normal saline once daily for 7 d. After the last administration of 1 h, mice in the other groups except the control group were treated with 10 mg/kg LPS solution to replicate the acute lung injury model of mice. After 6 h, the left lung tissues of each group were collected and the lung wet/dry mass ratio (W/D) was calculated. HE staining was used to observe the pathological changes of lung tissue. The serum levels of TNF-α and IL-6 were detected by ELISA. Western blotting method was used to detect the protein expressions of cGAS and STING in lung tissue. Results Compared with model group, the left lung W/D ratio, serum IL-6 and TNF-α levels, and the protein expressions of cGAS and STING in lung tissue were significantly decreased (P < 0.05), and the lung histopathological injuries were improved. Conclusion Sarsasapogenin may protect LPS-induced acute lung injury by inhibiting the cGAS-STING pathway and then reducing the secretion of inflammatory factors TNF-α and IL-6.

R285.5

國(guó)家自然科學(xué)基金資助項(xiàng)目（82100093）；鄭州大學(xué)第一附屬醫(yī)院青年創(chuàng)新基金資助項(xiàng)目（YNQN2017050）；河南省醫(yī)學(xué)科技攻關(guān)計(jì)劃省部共建項(xiàng)目（SBGJ202102166）