摘要
目的 评价雷公藤红素对高脂饮食诱导的代谢相关脂肪性肝病(MAFLD)大鼠的保护作用,并探讨其可能的作用机制。方法 60只健康雄性Wistar大鼠,随机分为6组:对照组、模型组、水飞蓟素胶囊组(阳性对照,100 mg·kg^(-1))和雷公藤红素低、中、高剂量(125、250、500μg·kg^(-1))组,每组10只。对照组给予普通饲料喂养,其余5组给予高脂饲料喂养建立MAFLD模型,造模4周后,从第5周开始给药,ig给予相应剂量的药物至第8周。记录大鼠体质量和肝脏湿质量,计算肝脏系数;腹主动脉取血,检测大鼠血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白-胆固醇(LDL-C)、高密度脂蛋白-胆固醇(HDL-C)、肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)水平;HE染色观察肝脏病理变化;Western blotting法检测肝脏中NOD样受体热蛋白结构域相关蛋白3(NLRP3)和半胱氨酸蛋白酶-1(Caspase-1)蛋白表达水平。结果 与模型组比较,雷公藤红素各剂量组的肝脏病理学表现均有所改善,肝脏系数均显著降低(P<0.05、0.01);中、高剂量组大鼠血清中TC、TG、LDL-C、AST、ALT、TNF-α和IL-1β水平均显著降低(P<0.05、0.01);肝脏中NLRP3和Caspase-1的蛋白表达显著减少(P<0.05、0.01)。结论 雷公藤红素可明显减轻MAFLD大鼠的肝脏病理学损伤,改善血脂水平,其机制可能与调控NLRP3通路密切相关。
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.
作者
景铭
王美灵
张媛媛
张红
梁皓楠
赵亚南
周辉
辛文妤
JING Ming;WANG Meiling;ZHANG Yuanyuan;ZHANG Hong;LIANG Haonan;ZHAO Yanan;ZHOU Hui;XIN Wenyu(School of Pharmacy,Binzhou Medical University,Yantai 264003,China;School of Pharmacy,Yantai University,Yantai 264005,China)
出处
《药物评价研究》
CAS
2022年第4期624-632,共9页
Drug Evaluation Research
基金
国家自然科学基金项目(81803546)
山东省自然基金项目(ZR2018LH024)
科研启动基金项目(BY2013KYQD09)。
关键词
雷公藤红素
代谢相关脂肪性肝病
NLRP3炎症小体
炎症反应
celastrol
metabolic dysfunction-associated fatty liver disease
NLRP3 inflammasome
inflammatory reaction
