首页|基于经典焦亡通路探讨祛湿活血方治疗NASH小鼠的作用机制

基于经典焦亡通路探讨祛湿活血方治疗NASH小鼠的作用机制

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目的 基于NLRP3/Caspasse-1/GSDMD经典焦亡通路探讨祛湿活血方治疗蛋氨酸-胆碱缺乏(MCD)饮食诱导非酒精性脂肪性肝炎(NASH)小鼠的作用机制。方法 将64只C57BL/6J雄性小鼠随机分为MCS对照组(A组)，MCD模型组(B组)，中药高、中、低剂量组(C、D、E组)，其中A组与B组各12只，其余组各10只。除A组使用蛋-氨酸-胆碱充足(MCS)饮食，其余组均使用MCD饮食4周进行NASH造模，A组与B组随机处死2只使用HE染色及油红O染色肝组织进行模型验证。4周后对A组与B组进行生理盐水灌胃，C、D、E组各使用不同浓度祛湿活血方灌胃，各组继续予原饮食方案喂养。4周后ELISA检测小鼠血清肝功能及炎症因子水平、HE染色观察小鼠肝组织脂质沉积及炎症细胞浸润情况、PCR检测焦亡相关基因(NLRP3/Caspase-1/GSDMD)表达以及蛋白免疫印迹检测上述蛋白表达情况。结果 与B组相比:其余四组小鼠血清中的炎症因子均有不同程度降低，病理结果也显示其余四组小鼠的肝内脂质沉积及炎症簇也较B组明显减少。PCR与Western Blot结果显示其余四组的NLRP3、Caspase-1、GSDMD的mRNA及蛋白含量均降低。结论 祛湿活血方可以改善NASH小鼠的肝脏炎症反应，减少肝脏脂质沉积，改善肝功能及胆汁代谢的作用，其具体分子机制与抑制NLRP3/Caspase-1/GSDMD通路有关。
Discussion on the Mechanism of Qushi Huoxue Formula in Treating NASH Mice Based on NLRP3/Caspase-1/GSDMD Pathway
Objective Based on the classic pyroptosis pathway of NLRP 3/Caspass-1/GSDMD,the mechanism of Qushi Huox-ue formula in treating non-alcoholic steatohepatitis(NASH)mice induced by MCD diet was discussed.Methods 64 C57BL/6J male mice were randomly divided into MCS control group(group A),MCD model group(group B)and high dose(group C),medium dose(group D)and low dose(group E)groups of Qushi Huoxue formula,with 12 mice in group A and B besides 10 mice in other groups.Except for group A,which was fed with MCS diet,the other groups were fed with MCD diet for 4 weeks to establish NASH model.Two rats in group A and group B were randomly selected to be killed,then used HE staining and oil red O staining to verify the model of NASH.Four weeks later,group A and group B were given normal saline to the stomach,while groups C,D and E were given different doses of Qushi Huoxue formula,and each group continued to be fed with the original diet.After four weeks,serum liver function and inflammatory factors were detected by ELISA,lipid deposition and inflammatory cell in-filtration in liver tissue were observed by HE staining.PCR was used to detect the expression of pyroptosis pathway-related genes(NLRP3/Caspase-1/GSDMD)and western blot was used to detect the expression of the above proteins.Results Compared with group B,the inflammatory factors in the serum of mice in the other four groups were reduced to varying degrees.Pathological re-sults also showed that the lipid deposition and inflammatory clusters in the liver of the other four groups of mice were significantly lower than those in group B.The results of PCR and Western Blot showed that the mRNA and protein contents of NLRP3,Caspase-1 and GSDMD in the other four groups decreased.Conclusion Qushi Huoxue formula can improve the liver inflammato-ry reaction,reduce liver lipid deposition and improve liver function and bile metabolism in NASH mice.Its specific molecular mechanism is related to the inhibition of NLRP3/Caspase-1/GSDMD pathway.

Qushi Huoxue FormulaNon-alcoholic mteatohepatitisPyroptosisInffammasomeNLRP3/Caspase-1/GSDMD pathway

吴铁雄、刘旭东、冉小柯、庞华珍、刘丽、唐艳芳

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广西中医药大学,广西南宁 530001

广西中医药大学附属瑞康医院,广西南宁 530001

祛湿活血方 非酒精性脂肪性肝炎 焦亡 炎症小体 NLRP3/Caspase-1/GSDMD通路

国家自然科学基金广西中医药大学一流学科建设项目(2019)广西中医药大学岐黄工程高层次人才培育项目中医药传承与创新人才培养平台建设项目(2019)广西中医药大学研究生教育创新计划广西(青年)岐黄学者培养项目(2022)

821608372019XK1392021007国中医药人教函[2019]41号XYJ22024

2024

10.3969/j.issn.1008-0805.2024.04.01

时珍国医国药
时珍国医国药杂志社

时珍国医国药

北大核心
影响因子：0.887
ISSN：1008-0805
年,卷(期)：2024.35(4)
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