目的 評價雷公藤紅素對高脂飲食誘導的代謝相關脂肪性肝病（MAFLD）大鼠的保護作用，并探討其可能的作用機制。方法 60只健康雄性Wistar大鼠，隨機分為6組：對照組、模型組、水飛薊素膠囊組（陽性對照，100 mg·kg⁻¹）和雷公藤紅素低、中、高劑量（125、250、500 μg·kg⁻¹）組，每組10只。對照組給予普通飼料喂養(yǎng)，其余5組給予高脂飼料喂養(yǎng)建立MAFLD模型，造模4周后，從第5周開始給藥，ig給予相應劑量的藥物至第8周。記錄大鼠體質(zhì)量和肝臟濕質(zhì)量，計算肝臟系數(shù)；腹主動脈取血，檢測大鼠血清中丙氨酸氨基轉(zhuǎn)移酶（ALT）、天冬氨酸氨基轉(zhuǎn)移酶（AST）、三酰甘油（TG）、總膽固醇（TC）、低密度脂蛋白-膽固醇（LDL-C）、高密度脂蛋白-膽固醇（HDL-C）、腫瘤壞死因子-α（TNF-α）和白細胞介素-1β（IL-1β）水平；HE染色觀察肝臟病理變化；Western blotting法檢測肝臟中NOD樣受體熱蛋白結(jié)構(gòu)域相關蛋白3（NLRP3）和半胱氨酸蛋白酶-1（Caspase-1）蛋白表達水平。結(jié)果 與模型組比較，雷公藤紅素各劑量組的肝臟病理學表現(xiàn)均有所改善，肝臟系數(shù)均顯著降低（P＜0.05、0.01）；中、高劑量組大鼠血清中TC、TG、LDL-C、AST、ALT、TNF_-α和IL-1β水平均顯著降低（P＜0.05、0.01）；肝臟中NLRP3和Caspase-1的蛋白表達顯著減少（P＜0.05、0.01）。結(jié)論 雷公藤紅素可明顯減輕MAFLD大鼠的肝臟病理學損傷，改善血脂水平，其機制可能與調(diào)控NLRP3通路密切相關。

Objective To evaluate the protective effect of celastrol on metabolic dysfunction-associated fatty liver disease (MAFLD) rats induced by high-fat diet and explore its possible mechanism. Method Sixty healthy male Wistar rats were randomly divided into six groups: control group, model group, silymarin capsules group (100 mg·kg^{−1), celastrol low dose group (125 μg·kg−1), middle dose group (250 μg·kg−1) and high dose group (500 μg·kg−1), with ten rats in each group. The control group was fed with normal diet, and the other five groups were fed with high-fat diet to establish MAFLD model. After four weeks, the rats were given medicine from the fifth week, and the corresponding dose was given by intragastric administration to the 8th week. The body weight and wet weight of liver were recorded. The blood of abdominal aorta was taken to detect the biochemical indexes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), triacylglycerol (TG), Total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), tumor necrosis factor - α (TNF- α) and interleukin-1 β (IL-1β) in rat serum. The pathological changes of liver tissue were observed by HE staining. The expression levels of NLRP3 and caspase-1 in liver were detected by Western blotting. Results Compared with the model group, the liver pathology of each celastrol group was improved. The liver index, the contents of TC, TG, LDL-C, AST and ALT in serum and the expression of NLRP3 and caspase-1 in liver in middle and high dose celastrol groups were significantly lower than those in model group (P < 0.05 and 0.01). Conclusion Celastrol can significantly reduce the liver pathological damage and improve the level of blood lipids in MAFLD rats, and its mechanism may be closely related to the regulation of NLRP3 pathway.}

R285.5

國家自然科學基金項目（81803546）；山東省自然基金項目（ZR2018LH024）；科研啟動基金項目（BY2013KYQD09）